US20030175700A1

US20030175700A1 - Compounds and methods for treatment and diagnosis of chlamydial infection

Info

Publication number: US20030175700A1
Application number: US09/841,260
Authority: US
Inventors: Ajay Bhatia; Peter Probst; Erika Stromberg
Original assignee: Corixa Corp
Current assignee: Corixa Corp
Priority date: 2000-04-21
Filing date: 2001-04-23
Publication date: 2003-09-18
Also published as: EP2192128A2; EP1278855A2; WO2001081379A3; ES2303525T3; WO2001081379A2; ATE389020T1; DE60133190T2; EP2192128A3; US20040137007A1; EP1278855B1; AU2001255596A1; CA2407114A1; US7384638B2; DE60133190D1

Abstract

Compounds and methods for the diagnosis and treatment of Chlamydial infection are disclosed. The compounds provided include polypeptides that contain at least one antigenic portion of a Chlamydia antigen and DNA sequences encoding such polypeptides. Pharmaceutical compositions and vaccines comprising such polypeptides or DNA sequences are also provided, together with antibodies directed against such polypeptides. Diagnostic kits containing such polypeptides or DNA sequences and a suitable detection reagent may be used for the detection of Chlamydial infection in patients and in biological samples.

Description

CROSS REFERENCE TO RELATED APPLICATIONS

This application is related to U.S. Provisioinal Application No. 60/198,853, filed Apr. 21, 2000, and U.S. Provisional Application No. 60/219,752, filed Jul. 20, 2000, incorporated in their entirety herein.[0001]

TECHNICAL FIELD

The present invention relates generally to the detection and treatment of Chlamydial infection. In particular, the invention is related to polypeptides comprising a Chlamydia antigen and the use of such polypeptides for the serodiagnosis and treatment of Chlamydial infection.

BACKGROUND OF THE INVENTION

Chlamydiae are intracellular bacterial pathogens that are responsible for a wide variety of important human and animal infections. Chlamydia trachomatis is one of the most common causes of sexually transmitted diseases and can lead to pelvic inflammatory disease (PID), resulting in tubal obstruction and infertility. Chlamydia trachomatis may also play a role in male infertility. In 1990, the cost of treating PID in the US was estimated to be $4 billion. Trachoma, due to ocular infection with Chlamydia trachomatis, is the leading cause of preventable blindness worldwide. Chlamydia pneumonia is a major cause of acute respiratory tract infections in humans and is also believed to play a role in the pathogenesis of atherosclerosis and, in particular, coronary heart disease. Individuals with a high titer of antibodies to Chlamydia pneumonia have been shown to be at least twice as likely to suffer from coronary heart disease as seronegative individuals. Chlamydial infections thus constitute a significant health problem both in the US and worldwide.

Chlamydial infection is often asymptomatic. For example, by the time a woman seeks medical attention for PID, irreversible damage may have already occurred resulting in infertility. There thus remains a need in the art for improved vaccines and pharmaceutical compositions for the prevention and treatment of Chlamydia infections. The present invention fulfills this need and further provides other related advantages.

SUMMARY OF THE INVENTION

The present invention provides compositions and methods for the diagnosis and therapy of Chlamydia infection. In one aspect, the present invention provides polypeptides comprising an immunogenic portion of a Chlamydia antigen, or a variant of such an antigen. Certain portions and other variants are immunogenic, such that the ability of the variant to react with antigen-specific antisera is not substantially diminished. Within certain embodiments, the polypeptide comprises an amino acid sequence encoded by a polynucleotide sequence selected from the group consisting of (a) a sequence of SEQ ID NO: 1-48, 114-121, and 125-138; (b) the complements of said sequences; and (c) sequences that hybridize to a sequence of (a) or (b) under moderately stringent conditions. In specific embodiments, the polypeptides of the present invention comprise at least a portion of a Chlamydial protein that includes an amino acid sequence selected from the group consisting of sequences recited in SEQ ID NO: 122-124 and 139-140 and variants thereof.

The present invention further provides polynucleotides that encode a polypeptide as described above, or a portion thereof (such as a portion encoding at least 15 amino acid residues of a Chlamydial protein), expression vectors comprising such polynucleotides and host cells transformed or transfected with such expression vectors.

In a related aspect, polynucleotide sequences encoding the above polypeptides, recombinant expression vectors comprising one or more of these polynucleotide sequences and host cells transformed or transfected with such expression vectors are also provided.

In another aspect, the present invention provides fusion proteins comprising an inventive polypeptide, or, alternatively, an inventive polypeptide and a known Chlamydia antigen, as well as polynucleotides encoding such fusion proteins, in combination with a physiologically acceptable carrier or immunostimulant for use as pharmaceutical compositions and vaccines thereof.

The present invention further provides pharmaceutical compositions that comprise: (a) an antibody, both polyclonal and monoclonal, or antigen-binding fragment thereof that specifically binds to a Chlamydial protein; and (b) a physiologically acceptable carrier. Within other aspects, the present invention provides pharmaceutical compositions that comprise one or more Chlamydia polypeptides disclosed herein, for example, a polypeptide of SEQ ID NO: 95-109, 122-124 and 139-140, or a polynucleotide molecule encoding such a polypeptide, such as a polynucleotide sequence of SEQ ID NO: 1-48, 80-94, 114-121 and 125-138, and a physiologically acceptable carrier. The invention also provides compositions for prophylactic and therapeutic purposes comprising one or more of the disclosed polynucleotides and/or polypeptides and an immunostimulant, e.g., an adjuvant.

In yet another aspect, methods are provided for stimulating an immune response in a patient, e.g., for inducing protective immunity in a patient, comprising administering to a patient an effective amount of one or more of the above pharmaceutical compositions or vaccines.

In yet a further aspect, methods for the treatment of Chlamydia infection in a patient are provided, the methods comprising obtaining peripheral blood mononuclear cells (PBMC) from the patient, incubating the PBMC with a polypeptide of the present invention (or a polynucleotide that encodes such a polypeptide) to provide incubated T cells and administering the incubated T cells to the patient. The present invention additionally provides methods for the treatment of Chlamydia infection that comprise incubating antigen presenting cells with a polypeptide of the present invention (or a polynucleotide that encodes such a polypeptide) to provide incubated antigen presenting cells and administering the incubated antigen presenting cells to the patient. Proliferated cells may, but need not, be cloned prior to administration to the patient. In certain embodiments, the antigen presenting cells are selected from the group consisting of dendritic cells, macrophages, monocytes, B-cells, and fibroblasts. Compositions for the treatment of Chlamydia infection comprising T cells or antigen presenting cells that have been incubated with a polypeptide or polynucleotide of the present invention are also provided. Within related aspects, vaccines are provided that comprise: (a) an antigen presenting cell that expresses a polypeptide as described above and (b) an immunostimulant.

The present invention further provides, within other aspects, methods for removing Chlamydial-infected cells from a biological sample, comprising contacting a biological sample with T cells that specifically react with a Chlamydial protein, wherein the step of contacting is performed under conditions and for a time sufficient to permit the removal of cells expressing the protein from the sample.

Within related aspects, methods are provided for inhibiting the development of Chlamydial infection in a patient, comprising administering to a patient a biological sample treated as described above. In further aspects of the subject invention, methods and diagnostic kits are provided for detecting Chlamydia infection in a patient. In one embodiment, the method comprises: (a) contacting a biological sample with at least one of the polypeptides or fusion proteins disclosed herein; and (b) detecting in the sample the presence of binding agents that bind to the polypeptide or fusion protein, thereby detecting Chlamydia infection in the biological sample. Suitable biological samples include whole blood, sputum, serum, plasma, saliva, cerebrospinal fluid and urine. In one embodiment, the diagnostic kits comprise one or more of the polypeptides or fusion proteins disclosed herein in combination with a detection reagent. In yet another embodiment, the diagnostic kits comprise either a monoclonal antibody or a polyclonal antibody that binds with a polypeptide of the present invention.

The present invention also provides methods for detecting Chlamydia infection comprising: (a) obtaining a biological sample from a patient; (b) contacting the sample with at least two oligonucleotide primers in a polymerase chain reaction, at least one of the oligonucleotide primers being specific for a polynucleotide sequence disclosed herein; and (c) detecting in the sample a polynucleotide sequence that amplifies in the presence of the oligonucleotide primers. In one embodiment, the oligonucleotide primer comprises at least about 10 contiguous nucleotides of a polynucleotide sequence peptide disclosed herein, or of a sequence that hybridizes thereto.

In a further aspect, the present invention provides a method for detecting Chlamydia infection in a patient comprising: (a) obtaining a biological sample from the patient; (b) contacting the sample with an oligonucleotide probe specific for a polynucleotide sequence disclosed herein; and (c) detecting in the sample a polynucleotide sequence that hybridizes to the oligonucleotide probe. In one embodiment, the oligonucleotide probe comprises at least about 15 contiguous nucleotides of a polynucleotide sequence disclosed herein, or a sequence that hybridizes thereto.

These and other aspects of the present invention will become apparent upon reference to the following detailed description. All references disclosed herein are hereby incorporated by reference in their entirety as if each was incorporated individually.

Sequence Identifiers

SEQ ID NO: 1 sets forth a DNA sequence identified for clone E4-A2-39 (CT10 positive) that is 1311 bp and contains the entire ORF for CT460 (SWIB) and a partial ORF for CT461 (yaeI).

SEQ ID NO: 2 sets forth a DNA sequence for clone E2-B10-52 (CT10 positive) that has a 1516 bp insert that contains partial ORFs for genes CT827 (nrdA-ribonucleoside reductase large chain) and CT828 (ndrB-ribonucleoside reductase small chain). These genes as were not identified in a Ct L2 library screening.

SEQ ID NO: 3 sets forth a DNA sequence for clone E1-B1-80 (CT10 positive) (2397 bp) that contains partial ORFs for several genes, CT812 (pmpD), CT015 (phoH ATPase), CT016 (hypothetical protein) and pGp1-D ( C. trachomatis plasmid gene).

SEQ ID NO: 4 sets forth a DNA sequence for clone E4-F9-4 (CT10, CL8, CT1, CT5, CT13, and CHH037 positive) that contains a 1094 bp insert that has a partial ORF for the gene CT316 (L7/L12 ribosomal protein) as well as a partial ORF for gene CT315 (RNA polymerase beta).

SEQ ID NO: 5 sets forth a DNA sequence for clone E2-H6-40 (CT3 positive) that has a 2129 bp insert that contains the entire ORF for the gene CT288 and very small fragments of genes CT287 and CT289. Genes in this clone have not been identified in screening with a Ct L2 library.

SEQ ID NO: 6 sets forth a DNA sequence for clone E5-D4-2 (CT3, CT10, CT1, CT5, CT12, and CHH037 positive) that has a 1828 bp insert that contains a partial ORF for gene CT378 (pgi), complete ORF for gene CT377 (ltuA) and a complete ORF for the gene CT376 (malate dehydrogenase). In addition, the patient lines CT10, CT1, CT5, CT12, and CHH037 also identified this clone.

SEQ ID NO: 7 sets forth a DNA sequence for clone E6-C1-31 (CT3 positive) that has a 861 bp insert that contains a partial ORF for gene CT858.

SEQ ID NO: 8 sets forth a DNA sequence for clone E9-E11-76 (CT3 positive) that contains a 763 bp insert that is an amino terminal region of the gene for CT798 (Glycogen synthase). This gene was not identified in a previous screening with a Ct L2 library.

SEQ ID NO: 9 sets forth a DNA sequence for clone E2-A9-26 (CT1-positive) that contains part of the gene for ORF-3 which is found on the plasmid in Chlamydia trachomatis.

SEQ ID NO: 10 sets forth a DNA sequence for clone E2-G8-94 (CT1-positive) that has the carboxy terminal end of Lpda gene as well as a partial ORF for CT556.

SEQ ID NO: 11 sets forth a DNA sequence for clone E1-H1-14 (CT1 positive) that has a 1474 bp insert that contains the amino terminal part of an Lpda ORF on the complementary strand.

SEQ ID NO: 12 sets forth a DNA sequence for clone E1-A5-53 (CT1 positive) that contains a 2017 bp insert that has an amino terminal portion of the ORF for dnaK gene on the complementary strand, a partial ORF for the grpE gene (CT395) and a partial ORF for CT166.

SEQ ID NO: 13 sets forth a DNA sequence for clone E3-A1-50 (positive on CT1 line) that is 1199 bp and contains a carboxy terminal portion of the ORF for CT622.

SEQ ID NO: 14 sets forth a DNA sequence for clone E3-E2-22 that has 877 bp, containing a complete ORF for CT610 on the complementary strand, and was positive on both CT3 and CT10 lines.

SEQ ID NO: 15 sets forth the DNA sequence for clone E5-E2-10 (CT10 positive) which is 427 bp and contains a partial ORF for the major outer membrane protein omp1.SEQ ID NO: 16 sets forth the DNA sequence for clone E2-D5-89 (516 bp) which is a CT10 positive clone that contains a partial ORF for pmpD gene (CT812).

SEQ ID NO: 17 sets forth the DNA sequence for clone E4-G9-75 (CT10 positive) which is 723 bp and contains a partial ORF for the amino terminal region of the pmpH gene (CT872).

SEQ ID NO: 18 sets forth the DNA sequence for clone E3-F2-37 (CT10, CT3, CT11, and CT13 positive-1377bp insert) which contains a partial ORF for the tRNA-Trp (CT322) gene and a complete ORF for the gene secE (CT321).

SEQ ID NO: 19 sets forth the DNA sequence for clone E5-A11-8 (CT10 positive-1736 bp) which contains the complete ORF for groES (CT111) and a majority of the ORF for groEL (CT110).

SEQ ID NO: 20 sets forth the DNA sequence for clone E7-H11-61 (CT3 positive-1135 bp) which has partial inserts for fliA (CT061), tyrS (CT062), TSA (CT603) and a hypothetical protein (CT602).

SEQ ID NO: 21 sets forth a DNA sequence for clone E6-C8-95 which contains a 731 bp insert that was identified using the donor lines CT3, CT1, and CT12 line. This insert has a carboxy terminal half for the gene for the 60 kDa ORF.

SEQ ID NO: 22 sets forth the DNA sequence for clone E4-D2-79 (CT3 positive) which contains a 1181 bp insert that is a partial ORF for nrdA gene. The ORF for this gene was also identified from clone E2-B10-52 (CT10 positive).

SEQ ID NO: 23 sets forth the DNA sequence for clone E1-F9-79 (167 bp; CT11 positive) which contains a partial ORF for the gene CT133 on the complementary strand. CT133 is a predicted rRNA methylase.

SEQ ID NO: 24 sets forth the DNA sequence for clone E2-G12-52 (1265 bp; CT11 positive) which contains a partial ORF for clpB, a protease ATPase.

SEQ ID NO: 25 sets forth the DNA sequence for clone E4-H3-56 (463 bp insert; CT1 positive) which contains a partial ORF for the TSA gene (CT603) on the complementary strand.

SEQ ID NO: 26 sets forth the DNA sequence for clone E5-E9-3 (CT1 positive) that contains a 636 bp insert partially encoding the ORF for dnaK like gene. Part of this sequence was also identified in clone E1-A5-53.

SEQ ID NO: 27 sets forth the full-length serovar E DNA sequence of CT875.

SEQ ID NO: 28 sets for the full-length serovar E DNA sequence of CT622.

SEQ ID NO: 29 sets forth the DNA sequence for clone E3-B4-18 (CT1 positive) that contains a 1224 bp insert containing 4 ORFs. The complete ORF for CT772, and the partial ORFs of CT771, CT191, and CT190.

SEQ ID NO: 30 sets forth the DNA sequence for the clone E9-E10-51 (CT10 positive) that contains an 883 bp insert containing two partial ORF, CT680 and CT679.

SEQ ID NO: 31 sets forth the DNA sequence of the clone E9-D5-8 (CT10, CTCT1, CT4, and CT11 positive) that contains a393 bp insert containing the partial ORF for CT680.

SEQ ID NO: 32 sets forth the DNA sequence of the clone E7-B1-16 (CT10, CT3, CT5, CT11, CT13, and CHH037 positive) that contains a 2577 bp insert containing three ORFs, two full length ORFs for CT694 and CT695 and the third containing the N-terminal portion of CT969.

SEQ ID NO: 33 sets forth the DNA sequence of the clone E9-G2-93 (CT10 positive) that contains a 554 bp insert containing a partial ORF for CT178.

SEQ ID NO: 34 sets forth the DNA sequence of the clone E5-A8-85 (CT1 positive) that contains a 1433 bp insert containing two partial ORFs for CT875 and CT001.

SEQ ID NO: 35 sets forth the DNA sequence of the clone E10-C6-45 (CT3 positive) that contains a 196 bp insert containing a partial ORF for CT827.

SEQ ID NO: 36 sets forth the DNA sequence of the clone E7-H11-10 (CT3 positive) that contains a 1990 bp insert containing the partial ORFs of CT610 and CT613 and the complete ORFs of CT611 and CT612.

SEQ ID NO: 37 sets forth the DNA sequence of the clone E2-F7-11 (CT3 and CT10 positive) that contains a 2093 bp insert. It contains a large region of CT609, a complete ORF for CT610 and a partial ORF for CT611.

SEQ ID NO: 38 sets forth the DNA sequence of the clone E3-A3-31 (CT1 positive) that contains an 1834 bp insert containing a large region of CT622.

SEQ ID NO: 39 sets forth the DNA sequence of the clone E1-G9-23 (CT3 positive) that contains an 1180 bp insert containing almost the entire ORF for CT798.

SEQ ID NO: 40 sets forth the DNA sequence of the clone E4-D6-21 (CT3 positive) that contains a 1297 bp insert containing the partial ORFs of CT329 and CT327 and the complete ORF of CT328.

SEQ ID NO: 41 sets forth the DNA sequence of the clone E3-F3-18 (CT1 positive) that contains an 1141 bp insert containing the partial ORF of CT871.

SEQ ID NO: 42 sets forth the DNA sequence of the clone E10-B2-57 (CT10 positive) that contains an 822 bp insert containing the complete ORF of CT066.

SEQ ID NO: 43 sets forth the DNA sequence of the clone E3-F3-7 (CT1 positive) that contains a 1643 bp insert containing the partial ORFs of CT869 and CT870.

SEQ ID NO: 44 sets forth the DNA sequence of the clone E10-H8-1 (CT3 and CT10 positive) that contains an 1862 bp insert containing the partial ORFs of CT871 and CT872.

SEQ ID NO: 45 sets forth the DNA sequence of the clone E3-D10-46 (CT1, CT3, CT4, CT11, and CT12 positive) that contains a 1666 bp insert containing the partial ORFs for CT770 and CT773 and the complete ORFs for CT771 and CT722.

SEQ ID NO: 46 sets forth the DNA sequence of the clone E2-D8-19 (CT1 positive) that contains a 2010 bp insert containing partial ORFs, ORF3 and ORF6, and complete ORFs, ORF4 and ORF5.

SEQ ID NO: 47 sets forth the DNA sequence of the clone E4-C3-40 (CT10 positive) that contains a 2044 bp insert containing the partial ORF for CT827 and a complete ORF for CT828.

SEQ ID NO: 48 sets forth the DNA sequence of the clone E3-H6-10 (CT12 positive) that contains a 3743 bp insert containing the partial ORFs for CT223 and CT229 and the complete ORFs for CT224 and CT224, CT225, CT226, CT227, and CT228.

SEQ ID NO: 49 sets forth the DNA sequence for the Chlamydia pneumoniae homologue, CPn0454 of the Chlamydia trachomatis gene CT872.

SEQ ID NO: 50 sets forth the DNA sequence for the Chlamydia pneumoniae homologue, CPn0187, of the Chlamydia trachomatis gene CT133.

SEQ ID NO: 51 sets forth the DNA sequence for the Chlamydia pneumoniae homologue, CPn0075 of the Chlamydia trachomatis gene CT321.

SEQ ID NO: 52 sets forth the DNA sequence for the Chlamydia pneumoniae homologue, CPn0074, of the Chlamydia trachomatis gene CT322.

SEQ ID NO: 53 sets forth the DNA sequence for the Chlamydia pneumoniae homologue, CPn0948, of the Chlamydia trachomatis gene CT798.

SEQ ID NO: 54 sets forth the DNA sequence for the Chlamydia pneumoniae homologue, CPn0985, of the Chlamydia trachomatis gene CT828.

SEQ ID NO: 55 sets forth the DNA sequence for the Chlamydia pneumoniae homologue, CPn0984, of the Chlamydia trachomatis gene CT827.

SEQ ID NO: 56 sets forth the DNA sequence for the Chlamydia pneumoniae homologue, CPn0062, of the Chlamydia trachomatis gene CT289.

SEQ ID NO: 57 sets forth the DNA sequence for the Chlamydia pneumoniae homologue, CPn00065, of the Chlamydia trachomatis gene CT288.

SEQ ID NO: 58 sets forth the DNA sequence for the Chlamydia pneumoniae homologue, CPn0438, of the Chlamydia trachomatis gene CT287.

SEQ ID NO: 59 sets forth the DNA sequence for the Chlamydia pneumoniae homologue, CPn0963, of the Chlamydia trachomatis gene CT812.

SEQ ID NO: 60 sets forth the DNA sequence for the Chlamydia pneumoniae homologue, CPn0778, of the Chlamydia trachomatis gene CT603.

SEQ ID NO: 61 sets forth the DNA sequence for the Chlamydia pneumoniae homologue, CPn0503, of the Chlamydia trachomatis gene CT396.

SEQ ID NO: 62 sets forth the DNA sequence for the Chlamydia pneumoniae homologue, CPn1016, of the Chlamydia trachomatis gene CT858.

SEQ ID NO: 63 sets forth the DNA sequence for the Chlamydia pneumoniae homologue, CPn0728, of the Chlamydia trachomatis gene CT622.

SEQ ID NO: 64 sets forth the DNA sequence for the Chlamydia pneumoniae homologue, CPn0557, of the Chlamydia trachomatis gene CT460.

SEQ ID NO: 65 sets forth the amino acid sequence for the Chlamydia pneumoniae homologue, CPn0454, of the Chlamydia trachomatis gene CT872.

SEQ ID NO: 66 sets forth the amino acid sequence for the Chlamydia pneumoniae homologue, CPn0187, of the Chlamydia trachomatis gene CT133.

SEQ ID NO: 67 sets forth the amino acid sequence for the Chlamydia pneumoniae homologue, CPn0075, of the Chlamydia trachomatis gene CT321.

SEQ ID NO: 68 sets forth the amino acid sequence for the Chlamydia pneumoniae homologue, CPn0074, of the Chlamydia trachomatis gene CT322.

SEQ ID NO: 69 sets forth the amino acid sequence for the Chlamydia pneumoniae homologue, CPn0948, of the Chlamydia trachomatis gene CT798.

SEQ ID NO: 70 sets forth the amino acid sequence for the Chlamydia pneumoniae homologue, CPn0985, of the Chlamydia trachomatis gene CT828.

SEQ ID NO: 71 sets forth the amino acid sequence for the Chlamydia pneumoniae homologue, CPn0984, of the Chlamydia trachomatis gene CT827.

SEQ ID NO: 72 sets forth the amino acid sequence for the Chlamydia pneumoniae homologue, CPn0062, of the Chlamydia trachomatis gene CT289.

SEQ ID NO: 73 sets forth the amino acid sequence for the Chlamydia pneumoniae homologue, CPn0065, of the Chlamydia trachomatis gene CT288.

SEQ ID NO: 74 sets forth the amino acid sequence for the Chlamydia pneumoniae homologue, CPn0438, of the Chlamydia trachomatis gene CT287.

SEQ ID NO: 75 sets forth the amino acid sequence for the Chlamydia pneumoniae homologue, CPn0963, of the Chlamydia trachomatis gene CT812.

SEQ ID NO: 76 sets forth the amino acid sequence for the Chlamydia pneumoniae homologue, CPn0778, of the Chlamydia trachomatis gene CT603.

SEQ ID NO: 77 sets forth the amino acid sequence for the Chlamydia pneumoniae homologue, CPn1016, of the Chlamydia trachomatis gene CT858.

SEQ ID NO: 78 sets forth the amino acid sequence for the Chlamydia pneumoniae homologue, CPn0728, of the Chlamydia trachomatis gene CT622.

SEQ ID NO: 79 sets forth the amino acid sequence for the Chlamydia pneumoniae homologue, CPn0557, of the Chlamydia trachomatis gene CT460.

SEQ ID NO: 80 sets forth the full-length serovar D DNA sequence of the Chlamydia trachomatis gene CT872.

SEQ ID NO: 81 sets forth the full-length serovar D DNA sequence of the Chlamydia trachomatis gene CT828.

SEQ ID NO: 82 sets forth the full-length serovar D DNA sequence of the Chlamydia trachomatis gene CT827.

SEQ ID NO: 83 sets forth the full-length serovar D DNA sequence of the Chlamydia trachomatis gene CT812.

SEQ ID NO: 84 sets forth the full-length serovar D DNA sequence of the Chlamydia trachomatis gene CT798.

SEQ ID NO: 85 sets forth the full-length serovar D DNA sequence of the Chlamydia trachomatis gene CT681 (MompF).

SEQ ID NO: 86 sets forth the full-length serovar D DNA sequence of the Chlamydia trachomatis gene CT603.

SEQ ID NO: 87 sets forth the full-length serovar D DNA sequence of the Chlamydia trachomatis gene CT460.

SEQ ID NO: 88 sets forth the full-length serovar D DNA sequence of the Chlamydia trachomatis gene CT322.

SEQ ID NO: 89 sets forth the full-length serovar D DNA sequence of the Chlamydia trachomatis gene CT321.

SEQ ID NO: 90 sets forth the full-length serovar D DNA sequence of the Chlamydia trachomatis gene CT289.

SEQ ID NO: 91 sets forth the full-length serovar D DNA sequence of the Chlamydia trachomatis gene CT288.

SEQ ID NO: 92 sets forth the full-length serovar D DNA sequence of the Chlamydia trachomatis gene CT287.

SEQ ID NO: 93 sets forth the full-length serovar D DNA sequence of the Chlamydia trachomatis gene CT 133.

SEQ ID NO: 94 sets forth the full-length serovar D DNA sequence of the Chlamydia trachomatis gene CT113.

SEQ ID NO: 95 sets forth the full-length serovar D amino acid sequence of the Chlamydia trachomatis gene CT872.

SEQ ID NO: 96 sets forth the full-length serovar D amino acid sequence of the Chlamydia trachomatis gene CT828.

SEQ ID NO: 97 sets forth the full-length serovar D amino acid sequence of the Chlamydia trachomatis gene CT827.

SEQ ID NO: 98 sets forth the full-length serovar D amino acid sequence of the Chlamydia trachomatis gene CT812.

SEQ ID NO: 99 sets forth the full-length serovar D amino acid sequence of the Chlamydia trachomatis gene CT798.

SEQ ID NO: 100 sets forth the full-length serovar D amino acid sequence of the Chlamydia trachomatis gene CT681.

SEQ ID NO: 101 sets forth the full-length serovar D amino acid sequence of the Chlamydia trachomatis gene CT603.

SEQ ID NO: 102 sets forth the full-length serovar D amino acid sequence of the Chlamydia trachomatis gene CT460.

SEQ ID NO: 103 sets forth the full-length serovar D amino acid sequence of the Chlamydia trachomatis gene CT322.

SEQ ID NO: 104 sets forth the full-length serovar D amino acid sequence of the Chlamydia trachomatis gene CT321.

SEQ ID NO: 105 sets forth the full-length serovar D amino acid sequence of the Chlamydia trachomatis gene CT289.

SEQ ID NO: 106 sets forth the full-length serovar D amino acid sequence of the Chlamydia trachomatis gene CT288.

SEQ ID NO: 107 sets forth the full-length serovar D amino acid sequence of the Chlamydia trachomatis gene CT287.

SEQ ID NO: 108 sets forth the full-length serovar D amino acid sequence of the Chlamydia trachomatis gene CT133.

SEQ ID NO: 109 sets forth the full-length serovar D amino acid sequence of the Chlamydia trachomatis gene CT113.

SEQ ID NO: 110 sets forth the DNA sequence for the Chlamydia pneumoniae homologue, CPn0695, of the Chlamydia trachomatis gene CT681.

SEQ ID NO: 111 sets forth the DNA sequence for the Chlamydia pneumoniae homologue, CPn0144, of the Chlamydia trachomatis gene CT113.

SEQ ID NO: 112 sets forth the amino acid sequence for the Chlamydia pneumoniae homologue, CPn0695, of the Chlamydia trachomatis gene CT681.

SEQ ID NO: 113 sets forth the amino acid sequence for the Chlamydia pneumoniae homologue, CPn0144, of the Chlamydia trachomatis gene CT 113.

SEQ ID NO: 114 sets forth the DNA sequence of the clone E7-B12-65 (CHH037 positive) that contains a 1179 bp insert containing complete ORF for 376.

SEQ ID NO: 115 sets forth the DNA sequence of the clone E4-H9-83 (CHH037 positive) that contains the partial ORF for the heat shock protein GroEL (CT110).

SEQ ID NO: 116 sets forth the DNA sequence of the clone E9-B10-52 (CHH037 positive) that contains the partial ORF for the the gene yscC (CT674).

SEQ ID NO: 117 sets forth the DNA sequence of the clone E7-A7-79 (CHH037 positive) that contains the complete ORF for the histone like development gene hctA (CT743) and a partial ORF for the rRNA methyltransferase gene ygcA (CT742).

SEQ ID NO: 118 sets forth the DNA sequence of the clone E2-D 11-18 (CHH037 positive) that contains the partial ORF for hctA (CT743).

SEQ ID NO: 119 sets forth the DNA sequence for the Chlamydia trachomatis serovar E hypothetical protein CT694.

SEQ ID NO: 120 sets forth the DNA sequence for the Chlamydia trachomatis serovar E hypothetical protein CT695.

SEQ ID NO: 121 sets forth the DNA sequence for the Chlamydia trachomatis serovar E L1 ribosomal protein.

SEQ ID NO: 122 sets forth the amino acid sequence for the Chlamydia trachomatis serovar E hypothetical protein CT694.

SEQ ID NO: 123 sets forth the amino acid sequence for the Chlamydia trachomatis serovar E hypothetical protein CT695.

SEQ ID NO: 124 sets forth the amino acid sequence for the Chlamydia trachomatis serovar E L1 ribosomal protein.

SEQ ID NO: 125 sets forth the DNA sequence of the clone E9-H6-15 (CT3 positive) that contains the partial ORF for the pmpB gene (CT413).

SEQ ID NO: 126 sets forth the DNA sequence of the clone E3-D10-87 (CT1 positive) that contains the partial ORFs for the hypothetical genes CT388 and CT389.

SEQ ID NO: 127 sets forth the DNA sequence of the clone E9-D6-43 (CT3 positive) that contains the partial ORF for the CT858.

SEQ ID NO: 128 sets forth the DNA sequence of the clone E3-D10-4 (CT1 positive) that contains the partial ORF for pGP3-D, an ORF encoded on the plasmid pCHL1.

SEQ ID NO: 129 sets forth the DNA sequence of the clone E3-G8-7 (CT1 positive) that contains the partial ORFs for the CT557 (LpdA) and CT558 (LipA).

SEQ ID NO: 130 sets forth the DNA sequence of the clone E3-F 11-32 (CT1 positive) that contains the partial ORF for pmpD (CT812).

SEQ ID NO: 131 sets forth the DNA sequence of the clone E2-F8-5 (CT12 positive) that contains the complete ORF for the 15 kDa ORF (CT442) and a partial ORF for the 60 kDa ORF (CT443).

SEQ ID NO: 132 sets forth the DNA sequence of the clone E2-G4-39 (CT12 positive) that contains the partial ORF for the 60 kDa ORF (CT443).

SEQ ID NO: 133 sets forth the DNA sequence of the clone E9-D1-16 (CT10 positive) that contains the partial ORF for pmpH (CT872).

SEQ ID NO: 134 sets forth the DNA sequence of the clone E3-F3-6 (CT1 positive) that contains the partial ORFs for the genes accB (CT123), L1 ribosomal (CT125) and S9 ribosomal (CT126).

SEQ ID NO: 135 sets forth the DNA sequence of the clone E2-D4-70 (CT12 positive) that contains the partial ORF for the pmpC gene (CT414).

SEQ ID NO: 136 sets forth the DNA sequence of the clone E5-A1-79 (CT1 positive) that contains the partial ORF for ydhO (CT127), a complete ORF for S9 ribosomal gene (CT126), a complete ORF for the L1 ribosomal gene (CT125) and a partial ORF for accC (CT124).

SEQ ID NO: 137 sets forth the DNA sequence of the clone E1-F7-16 (CT12, CT3, and CT11 positive) that contains the partial ORF for the ftsH gene (CT841) and the entire ORF for the pnp gene (CT842).

SEQ ID NO: 138 sets forth the DNA sequence of the clone E1-D8-62 (CT12 positive) that contains the partial ORFs for the ftsH gene (CT841) and for the pnp gene (CT842).

SEQ ID NO: 139 sets forth the amino acid sequence for the serovar E protein CT875.

SEQ ID NO: 140 sets forth the amino acid sequence for the serovar E protein CT622.

DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

As noted above, the present invention is generally directed to compositions and methods for the diagnosis and treatment of Chlamydial infection. In one aspect, the compositions of the subject invention include polypeptides that comprise at least one immunogenic portion of a Chlamydia antigen, or a variant thereof.

In specific embodiments, the subject invention discloses polypeptides comprising an immunogenic portion of a Chlamydia antigen, wherein the Chlamydia antigen comprises an amino acid sequence encoded by a polynucleotide molecule including a sequence selected from the group consisting of (a) nucleotide sequences recited in SEQ ID NO: 1-48, 114-121, and 125-138 (b) the complements of said nucleotide sequences, and (c) variants of such sequences.

Polynucleotide Compositions

As used herein, the terms “DNA segment” and “polynucleotide” refer to a DNA molecule that has been isolated free of total genomic DNA of a particular species. Therefore, a DNA segment encoding a polypeptide refers to a DNA segment that contains one or more coding sequences yet is substantially isolated away from, or purified free from, total genomic DNA of the species from which the DNA segment is obtained. Included within the terms “DNA segment” and “polynucleotide” are DNA segments and smaller fragments of such segments, and also recombinant vectors, including, for example, plasmids, cosmids, phagemids, phage, viruses, and the like.

As will be understood by those skilled in the art, the DNA segments of this invention can include genomic sequences, extra-genomic and plasmid-encoded sequences and smaller engineered gene segments that express, or may be adapted to express, proteins, polypeptides, peptides and the like. Such segments may be naturally isolated, or modified synthetically by the hand of man.

“Isolated,” as used herein, means that a polynucleotide is substantially away from other coding sequences, and that the DNA segment does not contain large portions of unrelated coding DNA, such as large chromosomal fragments or other functional genes or polypeptide coding regions. Of course, this refers to the DNA segment as originally isolated, and does not exclude genes or coding regions later added to the segment by the hand of man.

As will be recognized by the skilled artisan, polynucleotides may be single-stranded (coding or antisense) or double-stranded, and may be DNA (genomic, cDNA or synthetic) or RNA molecules. RNA molecules include HnRNA molecules, which contain introns and correspond to a DNA molecule in a one-to-one manner, and mRNA molecules, which do not contain introns. Additional coding or non-coding sequences may, but need not, be present within a polynucleotide of the present invention, and a polynucleotide may, but need not, be linked to other molecules and/or support materials.

Polynucleotides may comprise a native Chlamydia sequence or may comprise a variant, or a biological or antigenic functional equivalent of such a sequence. Polynucleotide variants may contain one or more substitutions, additions, deletions and/or insertions, as further described below, preferably such that the immunogenicity of the encoded polypeptide is not diminished, relative to a native Chlamydia protein. The effect on the immunogenicity of the encoded polypeptide may generally be assessed as described herein. The term “variants” also encompasses homologous genes of xenogenic origin.

When comparing polynucleotide or polypeptide sequences, two sequences are said to be “identical” if the sequence of nucleotides or amino acids in the two sequences is the same when aligned for maximum correspondence, as described below. Comparisons between two sequences are typically performed by comparing the sequences over a comparison window to identify and compare local regions of sequence similarity. A “comparison window” as used herein, refers to a segment of at least about 20 contiguous positions, usually 30 to about 75, 40 to about 50, in which a sequence may be compared to a reference sequence of the same number of contiguous positions after the two sequences are optimally aligned.

Optimal alignment of sequences for comparison may be conducted using the Megalign program in the Lasergene suite of bioinformatics software (DNASTAR, Inc., Madison, Wis.), using default parameters. This program embodies several alignment schemes described in the following references: Dayhoff, M. O. (1978) A model of evolutionary change in proteins—Matrices for detecting distant relationships. In Dayhoff, M. O. (ed.) Atlas of Protein Sequence and Structure, National Biomedical Research Foundation, Washington D.C. Vol. 5, Suppl. 3, pp. 345-358; Hein J. (1990) Unified Approach to Alignment and Phylogenes pp. 626-645 Methods in Enzymology vol. 183, Academic Press, Inc., San Diego, Calif.; Higgins, D. G. and Sharp, P. M. (1989) CABIOS 5:151-153; Myers, E. W. and Muller W. (1988) CABIOS 4:11-17; Robinson, E. D. (1971) Comb. Theor 11:105; Santou, N. Nes, M. (1987) Mol. Biol. Evol. 4:406-425; Sneath, P. H. A. and Sokal, R. R. (1973) Numerical Taxonomy—the Principles and Practice of Numerical Taxonomy, Freeman Press, San Francisco, Calif.; Wilbur, W. J. and Lipman, D. J. (1983) Proc. Natl. Acad., Sci. USA 80:726-730.

Alternatively, optimal alignment of sequences for comparison may be conducted by the local identity algorithm of Smith and Waterman (1981) Add. APL. Math 2:482, by the identity alignment algorithm of Needleman and Wunsch (1970) J. Mol. Biol. 48:443, by the search for similarity methods of Pearson and Lipman (1988) Proc. Natl. Acad. Sci. USA 85: 2444, by computerized implementations of these algorithms (GAP, BESTFIT, BLAST, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group (GCG), 575 Science Dr., Madison, Wis.), or by inspection.

One preferred example of algorithms that are suitable for determining percent sequence identity and sequence similarity are the BLAST and BLAST 2.0 algorithms, which are described in Altschul et al. (1977) Nucl. Acids Res. 25:3389-3402 and Altschul et al. (1990) J. Mol. Biol. 215:403-410, respectively. BLAST and BLAST 2.0 can be used, for example with the parameters described herein, to determine percent sequence identity for the polynucleotides and polypeptides of the invention. Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information. In one illustrative example, cumulative scores can be calculated using, for nucleotide sequences, the parameters M (reward score for a pair of matching residues; always >0) and N (penalty score for mismatching residues; always <0). For amino acid sequences, a scoring matrix can be used to calculate the cumulative score. Extension of the word hits in each direction are halted when: the cumulative alignment score falls off by the quantity X from its maximum achieved value; the cumulative score goes to zero or below, due to the accumulation of one or more negative-scoring residue alignments; or the end of either sequence is reached. The BLAST algorithm parameters W, T and X determine the sensitivity and speed of the alignment. The BLASTN program (for nucleotide sequences) uses as defaults a wordlength (W) of 11, and expectation (E) of 10, and the BLOSUM62 scoring matrix (see Henikoff and Henikoff (1989) Proc. Natl. Acad. Sci. USA 89:10915) alignments, (B) of 50, expectation (E) of 10, M=5, N=−4 and a comparison of both strands.

Preferably, the “percentage of sequence identity” is determined by comparing two optimally aligned sequences over a window of comparison of at least 20 positions, wherein the portion of the polynucleotide or polypeptide sequence in the comparison window may comprise additions or deletions (i.e., gaps) of 20 percent or less, usually 5 to 15 percent, or 10 to 12 percent, as compared to the reference sequences (which does not comprise additions or deletions) for optimal alignment of the two sequences. The percentage is calculated by determining the number of positions at which the identical nucleic acid bases or amino acid residue occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the reference sequence (i.e., the window size) and multiplying the results by 100 to yield the percentage of sequence identity.

Therefore, the present invention encompasses polynucleotide and polypeptide sequences having substantial identity to the sequences disclosed herein, for example those comprising at least 50% sequence identity, preferably at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or higher, sequence identity compared to a polynucleotide or polypeptide sequence of this invention using the methods described herein, (e.g., BLAST analysis using standard parameters, as described below). One skilled in this art will recognize that these values can be appropriately adjusted to determine corresponding identity of proteins encoded by two nucleotide sequences by taking into account codon degeneracy, amino acid similarity, reading frame positioning and the like.

In additional embodiments, the present invention provides isolated polynucleotides and polypeptides comprising various lengths of contiguous stretches of sequence identical to or complementary to one or more of the sequences disclosed herein. For example, polynucleotides are provided by this invention that comprise at least about 15, 20, 30, 40, 50, 75, 100, 150, 200, 300, 400, 500 or 1000 or more contiguous nucleotides of one or more of the sequences disclosed herein as well as all intermediate lengths there between. It will be readily understood that “intermediate lengths”, in this context, means any length between the quoted values, such as 16, 17, 18, 19, etc.; 21, 22, 23, etc.; 30, 31, 32, etc.; 50, 51, 52, 53, etc.; 100, 101, 102, 103, etc.; 150, 151, 152, 153, etc.; including all integers through 200-500; 500-1,000, and the like.

The polynucleotides of the present invention, or fragments thereof, regardless of the length of the coding sequence itself, may be combined with other DNA sequences, such as promoters, polyadenylation signals, additional restriction enzyme sites, multiple cloning sites, other coding segments, and the like, such that their overall length may vary considerably. It is therefore contemplated that a nucleic acid fragment of almost any length may be employed, with the total length preferably being limited by the ease of preparation and use in the intended recombinant DNA protocol. For example, illustrative DNA segments with total lengths of about 10,000, about 5000, about 3000, about 2,000, about 1,000, about 500, about 200, about 100, about 50 base pairs in length, and the like, (including all intermediate lengths) are contemplated to be useful in many implementations of this invention.

In other embodiments, the present invention is directed to polynucleotides that are capable of hybridizing under moderately stringent conditions to a polynucleotide sequence provided herein, or a fragment thereof, or a complementary sequence thereof. Hybridization techniques are well known in the art of molecular biology. For purposes of illustration, suitable moderately stringent conditions for testing the hybridization of a polynucleotide of this invention with other polynucleotides include prewashing in a solution of 5×SSC, 0.5% SDS, 1.0 mM EDTA (pH 8.0); hybridizing at 50° C.-65° C., 5×SSC, overnight; followed by washing twice at 65° C. for 20 minutes with each of 2×, 0.5× and 0.2×SSC containing 0.1% SDS.

Moreover, it will be appreciated by those of ordinary skill in the art that, as a result of the degeneracy of the genetic code, there are many nucleotide sequences that encode a polypeptide as described herein. Some of these polynucleotides bear minimal homology to the nucleotide sequence of any native gene. Nonetheless, polynucleotides that vary due to differences in codon usage are specifically contemplated by the present invention. Further, alleles of the genes comprising the polynucleotide sequences provided herein are within the scope of the present invention. Alleles are endogenous genes that are altered as a result of one or more mutations, such as deletions, additions and/or substitutions of nucleotides. The resulting mRNA and protein may, but need not, have an altered structure or function. Alleles may be identified using standard techniques (such as hybridization, amplification and/or database sequence comparison).

Probes and Primers

In other embodiments of the present invention, the polynucleotide sequences provided herein can be advantageously used as probes or primers for nucleic acid hybridization. As such, it is contemplated that nucleic acid segments that comprise a sequence region of at least about 15 nucleotide long contiguous sequence that has the same sequence as, or is complementary to, a 15 nucleotide long contiguous sequence disclosed herein will find particular utility. Longer contiguous identical or complementary sequences, e.g., those of about 20, 30, 40, 50, 100, 200, 500, 1000 (including all intermediate lengths) and even up to full length sequences will also be of use in certain embodiments.

The ability of such nucleic acid probes to specifically hybridize to a sequence of interest will enable them to be of use in detecting the presence of complementary sequences in a given sample. However, other uses are also envisioned, such as the use of the sequence information for the preparation of mutant species primers, or primers for use in preparing other genetic constructions.

Polynucleotide molecules having sequence regions consisting of contiguous nucleotide stretches of 10-14, 15-20, 30, 50, or even of 100-200 nucleotides or so (including intermediate lengths as well), identical or complementary to a polynucleotide sequence disclosed herein, are particularly contemplated as hybridization probes for use in, e.g., Southern and Northern blotting. This would allow a gene product, or fragment thereof, to be analyzed, both in diverse cell types and also in various bacterial cells. The total size of fragment, as well as the size of the complementary stretch(es), will ultimately depend on the intended use or application of the particular nucleic acid segment. Smaller fragments will generally find use in hybridization embodiments, wherein the length of the contiguous complementary region may be varied, such as between about 15 and about 100 nucleotides, but larger contiguous complementarity stretches may be used, according to the length complementary sequences one wishes to detect.

The use of a hybridization probe of about 15-25 nucleotides in length allows the formation of a duplex molecule that is both stable and selective. Molecules having contiguous complementary sequences over stretches greater than 15 bases in length are generally preferred, though, in order to increase stability and selectivity of the hybrid, and thereby improve the quality and degree of specific hybrid molecules obtained. One will generally prefer to design nucleic acid molecules having gene-complementary stretches of 15 to 25 contiguous nucleotides, or even longer where desired.

Hybridization probes may be selected from any portion of any of the sequences disclosed herein. All that is required is to review the sequence set forth in SEQ ID NO: 1-48, 114-121, and 125-138, or to any continuous portion of the sequence, from about 15-25 nucleotides in length up to and including the full length sequence, that one wishes to utilize as a probe or primer. The choice of probe and primer sequences may be governed by various factors. For example, one may wish to employ primers from towards the termini of the total sequence.

Small polynucleotide segments or fragments may be readily prepared by, for example, directly synthesizing the fragment by chemical means, as is commonly practiced using an automated oligonucleotide synthesizer. Also, fragments may be obtained by application of nucleic acid reproduction technology, such as the PCR™ technology of U.S. Pat. No. 4,683,202 (incorporated herein by reference), by introducing selected sequences into recombinant vectors for recombinant production, and by other recombinant DNA techniques generally known to those of skill in the art of molecular biology.

The nucleotide sequences of the invention may be used for their ability to selectively form duplex molecules with complementary stretches of the entire gene or gene fragments of interest. Depending on the application envisioned, one will typically desire to employ varying conditions of hybridization to achieve varying degrees of selectivity of probe towards target sequence. For applications requiring high selectivity, one will typically desire to employ relatively stringent conditions to form the hybrids, e.g., one will select relatively low salt and/or high temperature conditions, such as provided by a salt concentration of from about 0.02 M to about 0.15 M salt at temperatures of from about 50° C. to about 70° C. Such selective conditions tolerate little, if any, mismatch between the probe and the template or target strand, and would be particularly suitable for isolating related sequences.

Of course, for some applications, for example, where one desires to prepare mutants employing a mutant primer strand hybridized to an underlying template, less stringent (reduced stringency) hybridization conditions will typically be needed in order to allow formation of the heteroduplex. In these circumstances, one may desire to employ salt conditions such as those of from about 0.15 M to about 0.9 M salt, at temperatures ranging from about 20° C. to about 55° C. Cross-hybridizing species can thereby be readily identified as positively hybridizing signals with respect to control hybridizations. In any case, it is generally appreciated that conditions can be rendered more stringent by the addition of increasing amounts of formamide, which serves to destabilize the hybrid duplex in the same manner as increased temperature. Thus, hybridization conditions can be readily manipulated, and thus will generally be a method of choice depending on the desired results.

Polynucleotide Identification and Characterization

Polynucleotides may be identified, prepared and/or manipulated using any of a variety of well established techniques. For example, a polynucleotide may be identified, by screening a microarray of cDNAs for Chlamydia expression. Such screens may be performed, for example, using a Synteni microarray (Palo Alto, Calif.) according to the manufacturer's instructions (and essentially as described by Schena et al., Proc. Natl. Acad. Sci. USA 93:10614-10619, 1996 and Heller et al., Proc. Natl. Acad. Sci. USA 94:2150-2155, 1997). Alternatively, polynucleotides may be amplified from cDNA prepared from cells expressing the proteins described herein. Such polynucleotides may be amplified via polymerase chain reaction (PCR). For this approach, sequence-specific primers may be designed based on the sequences provided herein, and may be purchased or synthesized.

An amplified portion of a polynucleotide of the present invention may be used to isolate a full length gene from a suitable library (e.g., Chlamydia cDNA library) using well known techniques. Within such techniques, a library (cDNA or genomic) is screened using one or more polynucleotide probes or primers suitable for amplification. Preferably, a library is size-selected to include larger molecules. Random primed libraries may also be preferred for identifying 5′ and upstream regions of genes. Genomic libraries are preferred for obtaining introns and extending 5′ sequences.

For hybridization techniques, a partial sequence may be labeled (e.g., by nick-translation or end-labeling with ³²P) using well known techniques. A bacterial or bacteriophage library is then generally screened by hybridizing filters containing denatured bacterial colonies (or lawns containing phage plaques) with the labeled probe (see Sambrook et al., Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratories, Cold Spring Harbor, N.Y., 1989). Hybridizing colonies or plaques are selected and expanded, and the DNA is isolated for further analysis. cDNA clones may be analyzed to determine the amount of additional sequence by, for example, PCR using a primer from the partial sequence and a primer from the vector. Restriction maps and partial sequences may be generated to identify one or more overlapping clones. The complete sequence may then be determined using standard techniques, which may involve generating a series of deletion clones. The resulting overlapping sequences can then assembled into a single contiguous sequence. A full length cDNA molecule can be generated by ligating suitable fragments, using well known techniques.

Alternatively, there are numerous amplification techniques for obtaining a full length coding sequence from a partial cDNA sequence. Within such techniques, amplification is generally performed via PCR. Any of a variety of commercially available kits may be used to perform the amplification step. Primers may be designed using, for example, software well known in the art. Primers are preferably 22-30 nucleotides in length, have a GC content of at least 50% and anneal to the target sequence at temperatures of about 68° C. to 72° C. The amplified region may be sequenced as described above, and overlapping sequences assembled into a contiguous sequence.

One such amplification technique is inverse PCR (see Triglia et al., Nucl. Acids Res. 16:8186, 1988), which uses restriction enzymes to generate a fragment in the known region of the gene. The fragment is then circularized by intramolecular ligation and used as a template for PCR with divergent primers derived from the known region. Within an alternative approach, sequences adjacent to a partial sequence may be retrieved by amplification with a primer to a linker sequence and a primer specific to a known region. The amplified sequences are typically subjected to a second round of amplification with the same linker primer and a second primer specific to the known region. A variation on this procedure, which employs two primers that initiate extension in opposite directions from the known sequence, is described in WO 96/38591. Another such technique is known as “rapid amplification of cDNA ends” or RACE. This technique involves the use of an internal primer and an external primer, which hybridizes to a polyA region or vector sequence, to identify sequences that are 5′ and 3′ of a known sequence. Additional techniques include capture PCR (Lagerstrom et al., PCR Methods Applic. 1:111-19, 1991) and walking PCR (Parker et al., Nucl. Acids. Res. 19:3055-60, 1991). Other methods employing amplification may also be employed to obtain a full length cDNA sequence.

In certain instances, it is possible to obtain a full length cDNA sequence by analysis of sequences provided in an expressed sequence tag (EST) database, such as that available from GenBank. Searches for overlapping ESTs may generally be performed using well known programs (e.g. NCBI BLAST searches), and such ESTs may be used to generate a contiguous full length sequence. Full length DNA sequences may also be obtained by analysis of genomic fragments.

Polynucleotide Expression in Host Cells

In other embodiments of the invention, polynucleotide sequences or fragments thereof which encode polypeptides of the invention, or fusion proteins or functional equivalents thereof, may be used in recombinant DNA molecules to direct expression of a polypeptide in appropriate host cells. Due to the inherent degeneracy of the genetic code, other DNA sequences that encode substantially the same or a functionally equivalent amino acid sequence may be produced and these sequences may be used to clone and express a given polypeptide.

As will be understood by those of skill in the art, it may be advantageous in some instances to produce polypeptide-encoding nucleotide sequences possessing non-naturally occurring codons. For example, codons preferred by a particular prokaryotic or eukaryotic host can be selected to increase the rate of protein expression or to produce a recombinant RNA transcript having desirable properties, such as a half-life which is longer than that of a transcript generated from the naturally occurring sequence.

Moreover, the polynucleotide sequences of the present invention can be engineered using methods generally known in the art in order to alter polypeptide encoding sequences for a variety of reasons, including but not limited to, alterations which modify the cloning, processing, and/or expression of the gene product. For example, DNA shuffling by random fragmentation and PCR reassembly of gene fragments and synthetic oligonucleotides may be used to engineer the nucleotide sequences. In addition, site-directed mutagenesis may be used to insert new restriction sites, alter glycosylation patterns, change codon preference, produce splice variants, or introduce mutations, and so forth.

In another embodiment of the invention, natural, modified, or recombinant nucleic acid sequences may be ligated to a heterologous sequence to encode a fusion protein. For example, to screen peptide libraries for inhibitors of polypeptide activity, it may be useful to encode a chimeric protein that can be recognized by a commercially available antibody. A fusion protein may also be engineered to contain a cleavage site located between the polypeptide-encoding sequence and the heterologous protein sequence, so that the polypeptide may be cleaved and purified away from the heterologous moiety.

Sequences encoding a desired polypeptide may be synthesized, in whole or in part, using chemical methods well known in the art (see Caruthers, M. H. et al. (1980) Nucl. Acids Res. Symp. Ser. 215-223, Horn, T. et al. (1980) Nucl. Acids Res. Symp. Ser. 225-232). Alternatively, the protein itself may be produced using chemical methods to synthesize the amino acid sequence of a polypeptide, or a portion thereof. For example, peptide synthesis can be performed using various solid-phase techniques (Roberge, J. Y. et al. (1995) Science 269:202-204) and automated synthesis may be achieved, for example, using the ABI 431A Peptide Synthesizer (Perkin Elmer, Palo Alto, Calif.).

A newly synthesized peptide may be substantially purified by preparative high performance liquid chromatography (e.g., Creighton, T. (1983) Proteins, Structures and Molecular Principles, W H Freeman and Co., New York, N.Y.) or other comparable techniques available in the art. The composition of the synthetic peptides may be confirmed by amino acid analysis or sequencing (e.g., the Edman degradation procedure). Additionally, the amino acid sequence of a polypeptide, or any part thereof, may be altered during direct synthesis and/or combined using chemical methods with sequences from other proteins, or any part thereof, to produce a variant polypeptide.

In order to express a desired polypeptide, the nucleotide sequences encoding the polypeptide, or functional equivalents, may be inserted into appropriate expression vector, i.e., a vector which contains the necessary elements for the transcription and translation of the inserted coding sequence. Methods which are well known to those skilled in the art may be used to construct expression vectors containing sequences encoding a polypeptide of interest and appropriate transcriptional and translational control elements. These methods include in vitro recombinant DNA techniques, synthetic techniques, and in vivo genetic recombination. Such techniques are described in Sambrook, J. et al. (1989) Molecular Cloning, A Laboratory Manual, Cold Spring Harbor Press, Plainview, N.Y., and Ausubel, F. M. et al. (1989) Current Protocols in Molecular Biology, John Wiley & Sons, New York. N.Y.

A variety of expression vector/host systems may be utilized to contain and express polynucleotide sequences. These include, but are not limited to, microorganisms such as bacteria transformed with recombinant bacteriophage, plasmid, or cosmid DNA expression vectors; yeast transformed with yeast expression vectors; insect cell systems infected with virus expression vectors (e.g., baculovirus); plant cell systems transformed with virus expression vectors (e.g., cauliflower mosaic virus, CaMV; tobacco mosaic virus, TMV) or with bacterial expression vectors (e.g., Ti or pBR322 plasmids); or animal cell systems.

The “control elements” or “regulatory sequences” present in an expression vector are those non-translated regions of the vector--enhancers, promoters, 5′ and 3′ untranslated regions—which interact with host cellular proteins to carry out transcription and translation. Such elements may vary in their strength and specificity. Depending on the vector system and host utilized, any number of suitable transcription and translation elements, including constitutive and inducible promoters, may be used. For example, when cloning in bacterial systems, inducible promoters such as the hybrid lacZ promoter of the PBLUESCRIPT phagemid (Stratagene, La Jolla, Calif.) or PSPORT1 plasmid (Gibco BRL, Gaithersburg, Md.) and the like may be used. In mammalian cell systems, promoters from mammalian genes or from mammalian viruses are generally preferred. If it is necessary to generate a cell line that contains multiple copies of the sequence encoding a polypeptide, vectors based on SV40 or EBV may be advantageously used with an appropriate selectable marker.

In bacterial systems, a number of expression vectors may be selected depending upon the use intended for the expressed polypeptide. For example, when large quantities are needed, for example for the induction of antibodies, vectors which direct high level expression of fusion proteins that are readily purified may be used. Such vectors include, but are not limited to, the multifunctional E. coli cloning and expression vectors such as BLUESCRIPT (Stratagene), in which the sequence encoding the polypeptide of interest may be ligated into the vector in frame with sequences for the amino-terminal Met and the subsequent 7 residues of .beta.-galactosidase so that a hybrid protein is produced; pIN vectors (Van Heeke, G. and S. M. Schuster (1989) J. Biol. Chem. 264:5503-5509); and the like. pGEX Vectors (Promega, Madison, Wis.) may also be used to express foreign polypeptides as fusion proteins with glutathione S-transferase (GST). In general, such fusion proteins are soluble and can easily be purified from lysed cells by adsorption to glutathione-agarose beads followed by elution in the presence of free glutathione. Proteins made in such systems may be designed to include heparin, thrombin, or factor XA protease cleavage sites so that the cloned polypeptide of interest can be released from the GST moiety at will.

In the yeast, Saccharomyces cerevisiae, a number of vectors containing constitutive or inducible promoters such as alpha factor, alcohol oxidase, and PGH may be used. For reviews, see Ausubel et al. (supra) and Grant et al. (1987) Methods Enzymol. 153:516-544.

In cases where plant expression vectors are used, the expression of sequences encoding polypeptides may be driven by any of a number of promoters. For example, viral promoters such as the 35S and 19S promoters of CaMV may be used alone or in combination with the omega leader sequence from TMV (Takamatsu, N. (1987) EMBO J. 6:307-311. Alternatively, plant promoters such as the small subunit of RUBISCO or heat shock promoters may be used (Coruzzi, G. et al. (1984) EMBO J. 3:1671-1680; Broglie, R. et al. (1984) Science 224:838-843; and Winter, J. et al. (1991) Results Probl. Cell Differ. 17:85-105). These constructs can be introduced into plant cells by direct DNA transformation or pathogen-mediated transfection. Such techniques are described in a number of generally available reviews (see, for example, Hobbs, S. or Murry, L. E. in McGraw Hill Yearbook of Science and Technology (1992) McGraw Hill, New York, N.Y.; pp. 191-196).

An insect system may also be used to express a polypeptide of interest. For example, in one such system, Autographa califomica nuclear polyhedrosis virus (AcNPV) is used as a vector to express foreign genes in Spodoptera frugiperda cells or in Trichoplusia larvae. The sequences encoding the polypeptide may be cloned into a non-essential region of the virus, such as the polyhedrin gene, and placed under control of the polyhedrin promoter. Successful insertion of the polypeptide-encoding sequence will render the polyhedrin gene inactive and produce recombinant virus lacking coat protein. The recombinant viruses may then be used to infect, for example, S. frugiperda cells or Trichoplusia larvae in which the polypeptide of interest may be expressed (Engelhard, E. K. et al. (1994) Proc. Natl. Acad. Sci. 91 :3224-3227).

In mammalian host cells, a number of viral-based expression systems are generally available. For example, in cases where an adenovirus is used as an expression vector, sequences encoding a polypeptide of interest may be ligated into an adenovirus transcription/translation complex consisting of the late promoter and tripartite leader sequence. Insertion in a non-essential E1 or E3 region of the viral genome may be used to obtain a viable virus which is capable of expressing the polypeptide in infected host cells (Logan, J. and Shenk, T. (1984) Proc. Natl. Acad. Sci. 81:3655-3659). In addition, transcription enhancers, such as the Rous sarcoma virus (RSV) enhancer, may be used to increase expression in mammalian host cells.

Specific initiation signals may also be used to achieve more efficient translation of sequences encoding a polypeptide of interest. Such signals include the ATG initiation codon and adjacent sequences. In cases where sequences encoding the polypeptide, its initiation codon, and upstream sequences are inserted into the appropriate expression vector, no additional transcriptional or translational control signals may be needed. However, in cases where only coding sequence, or a portion thereof, is inserted, exogenous translational control signals including the ATG initiation codon should be provided. Furthermore, the initiation codon should be in the correct reading frame to ensure translation of the entire insert. Exogenous translational elements and initiation codons may be of various origins, both natural and synthetic. The efficiency of expression may be enhanced by the inclusion of enhancers which are appropriate for the particular cell system which is used, such as those described in the literature (Scharf, D. et al. (1994) Results Probl. Cell Differ. 20:125-162).

In addition, a host cell strain may be chosen for its ability to modulate the expression of the inserted sequences or to process the expressed protein in the desired fashion. Such modifications of the polypeptide include, but are not limited to, acetylation, carboxylation, glycosylation, phosphorylation, lipidation, and acylation. Post-translational processing which cleaves a “prepro” form of the protein may also be used to facilitate correct insertion, folding and/or function. Different host cells such as CHO, HeLa, MDCK, HEK293, and WI38, which have specific cellular machinery and characteristic mechanisms for such post-translational activities, may be chosen to ensure the correct modification and processing of the foreign protein.

For long-term, high-yield production of recombinant proteins, stable expression is E generally preferred. For example, cell lines which stably express a polynucleotide of interest may be transformed using expression vectors which may contain viral origins of replication and/or endogenous expression elements and a selectable marker gene on the same or on a separate vector. Following the introduction of the vector, cells may be allowed to grow for 1-2 days in an enriched media before they are switched to selective media. The purpose of the selectable marker is to confer resistance to selection, and its presence allows growth and recovery of cells which successfully express the introduced sequences. Resistant clones of stably transformed cells may be proliferated using tissue culture techniques appropriate to the cell type.

Any number of selection systems may be used to recover transformed cell lines. These include, but are not limited to, the herpes simplex virus thymidine kinase (Wigler, M. et al. (1977) Cell 11:223-32) and adenine phosphoribosyltransferase (Lowy, I. et al. (1990) Cell 22:817-23) genes which can be employed in tk.sup.- or aprt.sup.- cells, respectively. Also, antimetabolite, antibiotic or herbicide resistance can be used as the basis for selection; for example, dhfr which confers resistance to methotrexate (Wigler, M. et al. (1980) Proc. Natl. Acad. Sci. 77:3567-70); npt, which confers resistance to the aminoglycosides, neomycin and G-418 (Colbere-Garapin, F. et al (1981) J. Mol. Biol. 150:1-14); and als or pat, which confer resistance to chlorsulfuron and phosphinotricin acetyltransferase, respectively (Murry, supra). Additional selectable genes have been described, for example, trpB, which allows cells to utilize indole in place of tryptophan, or hisD, which allows cells to utilize histinol in place of histidine (Hartman, S. C. and R. C. Mulligan (1988) Proc. Natl. Acad. Sci 85:8047-51). Recently, the use of visible markers has gained popularity with such markers as anthocyanins, beta-glucuronidase and its substrate GUS, and luciferase and its substrate luciferin, being widely used not only to identify transformants, but also to quantify the amount of transient or stable protein expression attributable to a specific vector system (Rhodes, C. A. et al. (1995) Methods Mol. Biol. 55:121-131).

Although the presence/absence of marker gene expression suggests that the gene of interest is also present, its presence and expression may need to be confirmed. For example, if the sequence encoding a polypeptide is inserted within a marker gene sequence, recombinant cells containing sequences can be identified by the absence of marker gene function. Alternatively, a marker gene can be placed in tandem with a polypeptide-encoding sequence under the control of a single promoter. Expression of the marker gene in response to induction or selection usually indicates expression of the tandem gene as well.

Alternatively, host cells which contain and express a desired polynucleotide sequence may be identified by a variety of procedures known to those of skill in the art. These procedures include, but are not limited to, DNA-DNA or DNA-RNA hybridizations and protein bioassay or immunoassay techniques which include membrane, solution, or chip based technologies for the detection and/or quantification of nucleic acid or protein.

A variety of protocols for detecting and measuring the expression of polynucleotide-encoded products, using either polyclonal or monoclonal antibodies specific for the product are known in the art. Examples include enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA), and fluorescence activated cell sorting (FACS). A two-site, monoclonal-based immunoassay utilizing monoclonal antibodies reactive to two non-interfering epitopes on a given polypeptide may be preferred for some applications, but a competitive binding assay may also be employed. These and other assays are described, among other places, in Hampton, R. et al. (1990; Serological Methods, a Laboratory Manual, APS Press, St Paul. Minn.) and Maddox, D. E. et al. (1983; J. Exp. Med. 158:1211-1216).

A wide variety of labels and conjugation techniques are known by those skilled in the art and may be used in various nucleic acid and amino acid assays. Means for producing labeled hybridization or PCR probes for detecting sequences related to polynucleotides include oligolabeling, nick translation, end-labeling or PCR amplification using a labeled nucleotide. Alternatively, the sequences, or any portions thereof may be cloned into a vector for the production of an mRNA probe. Such vectors are known in the art, are commercially available, and may be used to synthesize RNA probes in vitro by addition of an appropriate RNA polymerase such as T7, T3, or SP6 and labeled nucleotides. These procedures may be conducted using a variety of commercially available kits. Suitable reporter molecules or labels, which may be used include radionuclides, enzymes, fluorescent, chemiluminescent, or chromogenic agents as well as substrates, cofactors, inhibitors, magnetic particles, and the like.

Host cells transformed with a polynucleotide sequence of interest may be cultured under conditions suitable for the expression and recovery of the protein from cell culture. The protein produced by a recombinant cell may be secreted or contained intracellularly depending on the sequence and/or the vector used. As will be understood by those of skill in the art, expression vectors containing polynucleotides of the invention may be designed to contain signal sequences which direct secretion of the encoded polypeptide through a prokaryotic or eukaryotic cell membrane. Other recombinant constructions may be used to join sequences encoding a polypeptide of interest to nucleotide sequence encoding a polypeptide domain which will facilitate purification of soluble proteins. Such purification facilitating domains include, but are not limited to, metal chelating peptides such as histidine-tryptophan modules that allow purification on immobilized metals, protein A domains that allow purification on immobilized immunoglobulin, and the domain utilized in the FLAGS extension/affinity purification system (Immunex Corp., Seattle, Wash.). The inclusion of cleavable linker sequences such as those specific for Factor XA or enterokinase (Invitrogen. San Diego, Calif.) between the purification domain and the encoded polypeptide may be used to facilitate purification. One such expression vector provides for expression of a fusion protein containing a polypeptide of interest and a nucleic acid encoding 6 histidine residues preceding a thioredoxin or an enterokinase cleavage site. The histidine residues facilitate purification on IMIAC (immobilized metal ion affinity chromatography) as described in Porath, J. et al. (1992, Prot. Exp. Purif. 3:263-281) while the enterokinase cleavage site provides a means for purifying the desired polypeptide from the fusion protein. A discussion of vectors which contain fusion proteins is provided in Kroll, D. J. et al. (1993; DNA Cell Biol. 12:441-453).

In addition to recombinant production methods, polypeptides of the invention, and fragments thereof, may be produced by direct peptide synthesis using solid-phase techniques (Merrifield J. (1963) J. Am. Chem. Soc. 85:2149-2154). Protein synthesis may be performed using manual techniques or by automation. Automated synthesis may be achieved, for example, using Applied Biosystems 431A Peptide Synthesizer (Perkin Elmer). Alternatively, various fragments may be chemically synthesized separately and combined using chemical methods to produce the full length molecule.

Site-Specific Mutagensis

Site-specific mutagenesis is a technique useful in the preparation of individual peptides, or biologically functional equivalent polypeptides, through specific mutagenesis of the underlying polynucleotides that encode them. The technique, well-known to those of skill in the art, further provides a ready ability to prepare and test sequence variants, for example, incorporating one or more of the foregoing considerations, by introducing one or more nucleotide sequence changes into the DNA. Site-specific mutagenesis allows the production of mutants through the use of specific oligonucleotide sequences which encode the DNA sequence of the desired mutation, as well as a sufficient number of adjacent nucleotides, to provide a primer sequence of sufficient size and sequence complexity to form a stable duplex on both sides of the deletion junction being traversed. Mutations may be employed in a selected polynucleotide sequence to improve, alter, decrease, modify, or otherwise change the properties of the polynucleotide itself, and/or alter the properties, activity, composition, stability, or primary sequence of the encoded polypeptide.

In certain embodiments of the present invention, the inventors contemplate the mutagenesis of the disclosed polynucleotide sequences to alter one or more properties of the encoded polypeptide, such as the antigenicity of a polypeptide vaccine. The techniques of site-specific mutagenesis are well-known in the art, and are widely used to create variants of both polypeptides and polynucleotides. For example, site-specific mutagenesis is often used to alter a specific portion of a DNA molecule. In such embodiments, a primer comprising typically about 14 to about 25 nucleotides or so in length is employed, with about 5 to about 10 residues on both sides of the junction of the sequence being altered.

As will be appreciated by those of skill in the art, site-specific mutagenesis techniques have often employed a phage vector that exists in both a single stranded and double stranded form. Typical vectors useful in site-directed mutagenesis include vectors such as the M13 phage. These phage are readily commercially-available and their use is generally well-known to those skilled in the art. Double-stranded plasmids are also routinely employed in site directed mutagenesis that eliminates the step of transferring the gene of interest from a plasmid to a phage.

In general, site-directed mutagenesis in accordance herewith is performed by first obtaining a single-stranded vector or melting apart of two strands of a double-stranded vector that includes within its sequence a DNA sequence that encodes the desired peptide. An oligonucleotide primer bearing the desired mutated sequence is prepared, generally synthetically. This primer is then annealed with the single-stranded vector, and subjected to DNA polymerizing enzymes such as E. coli polymerase I Kienow fragment, in order to complete the synthesis of the mutation-bearing strand. Thus, a heteroduplex is formed wherein one strand encodes the original non-mutated sequence and the second strand bears the desired mutation. This heteroduplex vector is then used to transform appropriate cells, such as E. coli cells, and clones are selected which include recombinant vectors bearing the mutated sequence arrangement.

The preparation of sequence variants of the selected peptide-encoding DNA segments using site-directed mutagenesis provides a means of producing potentially useful species and is not meant to be limiting as there are other ways in which sequence variants of peptides and the DNA sequences encoding them may be obtained. For example, recombinant vectors encoding the desired peptide sequence may be treated with mutagenic agents, such as hydroxylamine, to obtain sequence variants. Specific details regarding these methods and protocols are found in the teachings of Maloy et al., 1994; Segal, 1976; Prokop and Bajpai, 1991; Kuby, 1994; and Maniatis et al., 1982, each incorporated herein by reference, for that purpose.

As used herein, the term “oligonucleotide directed mutagenesis procedure” refers to template-dependent processes and vector-mediated propagation which result in an increase in the concentration of a specific nucleic acid molecule relative to its initial concentration, or in an increase in the concentration of a detectable signal, such as amplification. As used herein, the term “oligonucleotide directed mutagenesis procedure” is intended to refer to a process that involves the template-dependent extension of a primer molecule. The term template dependent process refers to nucleic acid synthesis of an RNA or a DNA molecule wherein the sequence of the newly synthesized strand of nucleic acid is dictated by the well-known rules of complementary base pairing (see, for example, Watson, 1987). Typically, vector mediated methodologies involve the introduction of the nucleic acid fragment into a DNA or RNA vector, the clonal amplification of the vector, and the recovery of the amplified nucleic acid fragment. Examples of such methodologies are provided by U.S. Pat. No. 4,237,224, specifically incorporated herein by reference in its entirety.

Polynucleotide Amplification Techniques

A number of template dependent processes are available to amplify the target sequences of interest present in a sample. One of the best known amplification methods is the polymerase chain reaction (PCR™) which is described in detail in U.S. Pat. Nos. 4,683,195, 4,683,202 and 4,800,159, each of which is incorporated herein by reference in its entirety. Briefly, in PCR™, two primer sequences are prepared which are complementary to regions on opposite complementary strands of the target sequence. An excess of deoxynucleoside triphosphates is added to a reaction mixture along with a DNA polymerase (e.g., Taq polymerase). If the target sequence is present in a sample, the primers will bind to the target and the polymerase will cause the primers to be extended along the target sequence by adding on nucleotides. By raising and lowering the temperature of the reaction mixture, the extended primers will dissociate from the target to form reaction products, excess primers will bind to the target and to the reaction product and the process is repeated. Preferably reverse transcription and PCR™ amplification procedure may be performed in order to quantify the amount of mRNA amplified. Polymerase chain reaction methodologies are well known in the art.

Another method for amplification is the ligase chain reaction (referred to as LCR), disclosed in Eur. Pat. Appl. Publ. No. 320,308 (specifically incorporated herein by reference in its entirety). In LCR, two complementary probe pairs are prepared, and in the presence of the target sequence, each pair will bind to opposite complementary strands of the target such that they abut. In the presence of a ligase, the two probe pairs will link to form a single unit. By temperature cycling, as in PCR™, bound ligated units dissociate from the target and then serve as “target sequences” for ligation of excess probe pairs. U.S. Pat. No. 4,883,750, incorporated herein by reference in its entirety, describes an alternative method of amplification similar to LCR for binding probe pairs to a target sequence.

Qbeta Replicase, described in PCT Intl. Pat. Appl. Publ. No. PCT/US87/00880, incorporated herein by reference in its entirety, may also be used as still another amplification method in the present invention. In this method, a replicative sequence of RNA that has a region complementary to that of a target is added to a sample in the presence of an RNA polymerase. The polymerase will copy the replicative sequence that can then be detected.

An isothermal amplification method, in which restriction endonucleases and ligases are used to achieve the amplification of target molecules that contain nucleotide 5′-[(α-thio]tiphosphates in one strand of a restriction site (Walker et al., 1992, incorporated herein by reference in its entirety), may also be useful in the amplification of nucleic acids in the present invention.

Strand Displacement Amplification (SDA) is another method of carrying out isothermal amplification of nucleic acids which involves multiple rounds of strand displacement and synthesis, i.e. nick translation. A similar method, called Repair Chain Reaction (RCR) is another method of amplification which may be useful in the present invention and is involves annealing several probes throughout a region targeted for amplification, followed by a repair reaction in which only two of the four bases are present. The other two bases can be added as biotinylated derivatives for easy detection. A similar approach is used in SDA.

Sequences can also be detected using a cyclic probe reaction (CPR). In CPR, a probe having a 3′ and 5′ sequences of non-target DNA and an internal or “middle” sequence of the target protein specific RNA is hybridized to DNA which is present in a sample. Upon hybridization, the reaction is treated with RNaseH, and the products of the probe are identified as distinctive products by generating a signal that is released after digestion. The original template is annealed to another cycling probe and the reaction is repeated. Thus, CPR involves amplifying a signal generated by hybridization of a probe to a target gene specific expressed nucleic acid.

Still other amplification methods described in Great Britain Pat. Appl. No. 2 202 328, and in PCT Intl. Pat. Appl. Publ. No. PCT/US89/01025, each of which is incorporated herein by reference in its entirety, may be used in accordance with the present invention. In the former application, “modified” primers are used in a PCR-like, template and enzyme dependent synthesis. The primers may be modified by labeling with a capture moiety (e.g., biotin) and/or a detector moiety (e.g., enzyme). In the latter application, an excess of labeled probes is added to a sample. In the presence of the target sequence, the probe binds and is cleaved catalytically. After cleavage, the target sequence is released intact to be bound by excess probe. Cleavage of the labeled probe signals the presence of the target sequence.

Other nucleic acid amplification procedures include transcription-based amplification systems (TAS) (Kwoh et al., 1989; PCT Intl. Pat. Appl. Publ. No. WO 88/10315, incorporated herein by reference in its entirety), including nucleic acid sequence based amplification (NASBA) and 3SR. In NASBA, the nucleic acids can be prepared for amplification by standard phenol/chloroform extraction, heat denaturation of a sample, treatment with lysis buffer and minispin columns for isolation of DNA and RNA or guanidinium chloride extraction of RNA. These amplification techniques involve annealing a primer that has sequences specific to the target sequence. Following polymerization, DNA/RNA hybrids are digested with RNase H while double stranded DNA molecules are heat-denatured again. In either case the single stranded DNA is made fully double stranded by addition of second target-specific primer, followed by polymerization. The double stranded DNA molecules are then multiply transcribed by a polymerase such as T7 or SP6. In an isothermal cyclic reaction, the RNAs are reverse transcribed into DNA, and transcribed once again with a polymerase such as T7 or SP6. The resulting products, whether truncated or complete, indicate target-specific sequences.

Eur. Pat. Appl. Publ. No. 329,822, incorporated herein by reference in its entirety, disclose a nucleic acid amplification process involving cyclically synthesizing single-stranded RNA (“ssRNA”), ssDNA, and double-stranded DNA (dsDNA), which may be used in accordance with the present invention. The ssRNA is a first template for a first primer oligonucleotide, which is elongated by reverse transcriptase (RNA-dependent DNA polymerase). The RNA is then removed from resulting DNA:RNA duplex by the action of ribonuclease H (RNase H, an RNase specific for RNA in a duplex with either DNA or RNA). The resultant ssDNA is a second template for a second primer, which also includes the sequences of an RNA polymerase promoter (exemplified by T7 RNA polymerase) 5′ to its homology to its template. This primer is then extended by DNA polymerase (exemplified by the large “Klenow” fragment of E. coli DNA polymerase I), resulting as a double-stranded DNA (“dsDNA”) molecule, having a sequence identical to that of the original RNA between the primers and having additionally, at one end, a promoter sequence. This promoter sequence can be used by the appropriate RNA polymerase to make many RNA copies of the DNA. These copies can then re-enter the cycle leading to very swift amplification. With proper choice of enzymes, this amplification can be done isothermally without addition of enzymes at each cycle. Because of the cyclical nature of this process, the starting sequence can be chosen to be in the form of either DNA or RNA.

PCT Intl. Pat. Appl. Publ. No. WO 89/06700, incorporated herein by reference in its entirety, disclose a nucleic acid sequence amplification scheme based on the hybridization of a promoter/primer sequence to a target single-stranded DNA (“ssDNA”) followed by transcription of many RNA copies of the sequence. This scheme is not cyclic; i.e. new templates are not produced from the resultant RNA transcripts. Other amplification methods include “RACE” (Frohman, 1990), and “one-sided PCR” (Ohara, 1989) which are well-known to those of skill in the art.

Methods based on ligation of two (or more) oligonucleotides in the presence of nucleic acid having the sequence of the resulting “di-oligonucleotide”, thereby amplifying the di-oligonucleotide (Wu and Dean, 1996, incorporated herein by reference in its entirety), may also be used in the amplification of DNA sequences of the present invention.

Biological Functional Equivalents

Modification and changes may be made in the structure of the polynucleotides and polypeptides of the present invention and still obtain a functional molecule that encodes a polypeptide with desirable characteristics. As mentioned above, it is often desirable to introduce one or more mutations into a specific polynucleotide sequence. In certain circumstances, the resulting encoded polypeptide sequence is altered by this mutation, or in other cases, the sequence of the polypeptide is unchanged by one or more mutations in the encoding polynucleotide.

When it is desirable to alter the amino acid sequence of a polypeptide to create an equivalent, or even an improved, second-generation molecule, the amino acid changes may be achieved by changing one or more of the codons of the encoding DNA sequence, according to Table 1.

For example, certain amino acids may be substituted for other amino acids in a protein structure without appreciable loss of interactive binding capacity with structures such as, for example, antigen-binding regions of antibodies or binding sites on substrate molecules. Since it is the interactive capacity and nature of a protein that defines that protein's biological functional activity, certain amino acid sequence substitutions can be made in a protein sequence, and, of course, its underlying DNA coding sequence, and nevertheless obtain a protein with like properties. It is thus contemplated by the inventors that various changes may be made in the peptide sequences of the disclosed compositions, or corresponding DNA sequences which encode said peptides without appreciable loss of their biological utility or activity.

TABLE 1


Amino Acids	Codons

Alanine	Ala	A	GCA GGG GCG GCU

Cysteine	Gys	C	UGG UGU

Aspartic acid	Asp	D	GAG GAU

Glutamic acid	Glu	B	GAA GAG

Phenylalanine	Phe	F	UUG UUU

Glycine	Gly	G	GGA GGG GGG GGU

Histidine	His	H	GAG GAU

Isoleucine	Ile	I	AUA AUG AUU

Lysine	Lys	K	AAA AAG

Leucine	Leu	L	UUA UUG GUA GUG GUG GUU

Methionine	Met	M	AUG

Asparagine	Asn	N	AAG AAU

Proline	Pro	P	GGA GGC GGG GGU

Glutamine	Gln	Q	GAA GAG

Arginine	Arg	R	AGA AGG GGA GGG GGG GGU

Serine	Ser	S	AGG AGU UGA UGG UGG UGU

Threonine	Thr	T	AGA ACG AGG AGU

Valine	Val	V	GUA GUG GUG GUU

Tryptophan	Trp	W	UGG

Tyrosine	Tyr	Y	UAG UAU

In making such changes, the hydropathic index of amino acids may be considered. The importance of the hydropathic amino acid index in conferring interactive biologic function on a protein is generally understood in the art (Kyte and Doolittle, 1982, incorporated herein by reference). It is accepted that the relative hydropathic character of the amino acid contributes to the secondary structure of the resultant protein, which in turn defines the interaction of the protein with other molecules, for example, enzymes, substrates, receptors, DNA, antibodies, antigens, and the like. Each amino acid has been assigned a hydropathic index on the basis of its hydrophobicity and charge characteristics (Kyte and Doolittle, 1982). These values are: isoleucine (+4.5); valine (+4.2); leucine (+3.8); phenylalanine (+2.8); cysteine/cystine (+2.5); methionine (+1.9); alanine (+1.8); glycine (−0.4); threonine (−0.7); serine (−0.8); tryptophan (−0.9); tyrosine (−1.3); proline (−1.6); histidine (−3.2); glutamate (−3.5); glutamine (−3.5); aspartate (−3.5); asparagine (−3.5); lysine (−3.9); and arginine (−4.5).

It is known in the art that certain amino acids may be substituted by other amino acids having a similar hydropathic index or score and still result in a protein with similar biological activity, i.e. still obtain a biological functionally equivalent protein. In making such changes, the substitution of amino acids whose hydropathic indices are within ±2 is preferred, those within ±1 are particularly preferred, and those within ±0.5 are even more particularly preferred. It is also understood in the art that the substitution of like amino acids can be made effectively on the basis of hydrophilicity. U.S. Pat. No. 4,554,101 (specifically incorporated herein by reference in its entirety), states that the greatest local average hydrophilicity of a protein, as governed by the hydrophilicity of its adjacent amino acids, correlates with a biological property of the protein.

As detailed in U.S. Pat. No. 4,554,101, the following hydrophilicity values have been assigned to amino acid residues: arginine (+3.0); lysine (+3.0); aspartate (+3.0±1); glutamate (+3.0±1); serine (+0.3); asparagine (+0.2); glutamine (+0.2); glycine (0); threonine (−0.4); proline (−0.5±1); alanine (−0.5); histidine (−0.5); cysteine (−1.0); methionine (−1.3); valine (−1.5); leucine (−1.8); isoleucine (−1.8); tyrosine (−2.3); phenylalanine (−2.5); tryptophan (−3.4). It is understood that an amino acid can be substituted for another having a similar hydrophilicity value and still obtain a biologically equivalent, and in particular, an immunologically equivalent protein. In such changes, the substitution of amino acids whose hydrophilicity values are within ±2 is preferred, those within ±1 are particularly preferred, and those within ±0.5 are even more particularly preferred.

As outlined above, amino acid substitutions are generally therefore based on the relative similarity of the amino acid side-chain substituents, for example, their hydrophobicity, hydrophilicity, charge, size, and the like. Exemplary substitutions that take various of the foregoing characteristics into consideration are well known to those of skill in the art and include: arginine and lysine; glutamate and aspartate; serine and threonine; glutamine and asparagine; and valine, leucine and isoleucine.

In addition, any polynucleotide may be further modified to increase stability in vivo. Possible modifications include, but are not limited to, the addition of flanking sequences at the 5′ and/or 3′ ends; the use of phosphorothioate or 2′ O-methyl rather than phosphodiesterase linkages in the backbone; and/or the inclusion of nontraditional bases such as inosine, queosine and wybutosine, as well as acetyl- methyl-, thio- and other modified forms of adenine, cytidine, guanine, thymine and uridine.

In Vivo Polynucleotide Delivery Techniques

In additional embodiments, genetic constructs comprising one or more of the polynucleotides of the invention are introduced into cells in vivo. This may be achieved using any of a variety or well known approaches, several of which are outlined below for the purpose of illustration.

1. Adenovirus

One of the preferred methods for in vivo delivery of one or more nucleic acid sequences involves the use of an adenovirus expression vector. “Adenovirus expression vector” is meant to include those constructs containing adenovirus sequences sufficient to (a) support packaging of the construct and (b) to express a polynucleotide that has been cloned therein in a sense or antisense orientation. Of course, in the context of an antisense construct, expression does not require that the gene product be synthesized.

The expression vector comprises a genetically engineered form of an adenovirus. Knowledge of the genetic organization of adenovirus, a 36 kb, linear, double-stranded DNA virus, allows substitution of large pieces of adenoviral DNA with foreign sequences up to 7 kb (Grunhaus and Horwitz, 1992). In contrast to retrovirus, the adenoviral infection of host cells does not result in chromosomal integration because adenoviral DNA can replicate in an episomal manner without potential genotoxicity. Also, adenoviruses are structurally stable, and no genome rearrangement has been detected after extensive amplification. Adenovirus can infect virtually all epithelial cells regardless of their cell cycle stage. So far, adenoviral infection appears to be linked only to mild disease such as acute respiratory disease in humans.

Adenovirus is particularly suitable for use as a gene transfer vector because of its mid-sized genome, ease of manipulation, high titer, wide target-cell range and high infectivity. Both ends of the viral genome contain 100-200 base pair inverted repeats (ITRs), which are cis elements necessary for viral DNA replication and packaging. The early (E) and late (L) regions of the genome contain different transcription units that are divided by the onset of viral DNA replication. The E1 region (E1A and E1B) encodes proteins responsible for the regulation of transcription of the viral genome and a few cellular genes. The expression of the E2 region (E2A and E2B) results in the synthesis of the proteins for viral DNA replication. These proteins are involved in DNA replication, late gene expression and host cell shut-off (Renan, 1990). The products of the late genes, including the majority of the viral capsid proteins, are expressed only after significant processing of a single primary transcript issued by the major late promoter (MLP). The MLP, (located at 16.8 m.u.) is particularly efficient during the late phase of infection, and all the mRNA's issued from this promoter possess a 5′-tripartite leader (TPL) sequence which makes them preferred mRNA's for translation.

In a current system, recombinant adenovirus is generated from homologous recombination between shuttle vector and provirus vector. Due to the possible recombination between two proviral vectors, wild-type adenovirus may be generated from this process. Therefore, it is critical to isolate a single clone of virus from an individual plaque and examine its genomic structure.

Generation and propagation of the current adenovirus vectors, which are replication deficient, depend on a unique helper cell line, designated 293, which was transformed from human embryonic kidney cells by Ad5 DNA fragments and constitutively expresses E1 proteins (Graham et al., 1977). Since the E3 region is dispensable from the adenovirus genome (Jones and Shenk, 1978), the current adenovirus vectors, with the help of 293 cells, carry foreign DNA in either the E1, the D3 or both regions (Graham and Prevec, 1991). In nature, adenovirus can package approximately 105% of the wild-type genome (Ghosh-Choudhury et al., 1987), providing capacity for about 2 extra kB of DNA. Combined with the approximately 5.5 kB of DNA that is replaceable in the E1 and E3 regions, the maximum capacity of the current adenovirus vector is under 7.5 kB, or about 15% of the total length of the vector. More than 80% of the adenovirus viral genome remains in the vector backbone and is the source of vector-borne cytotoxicity. Also, the replication deficiency of the E1-deleted virus is incomplete. For example, leakage of viral gene expression has been observed with the currently available vectors at high multiplicities of infection (MOI) (Mulligan, 1993).

Helper cell lines may be derived from human cells such as human embryonic kidney cells, muscle cells, hematopoietic cells or other human embryonic mesenchymal or epithelial cells. Alternatively, the helper cells may be derived from the cells of other mammalian species that are permissive for human adenovirus. Such cells include, e.g., Vero cells or other monkey embryonic mesenchymal or epithelial cells. As stated above, the currently preferred helper cell line is 293.

Recently, Racher et al. (1995) disclosed improved methods for culturing 293 cells and propagating adenovirus. In one format, natural cell aggregates are grown by inoculating individual cells into 1 liter siliconized spinner flasks (Techne, Cambridge, UK) containing 100-200 ml of medium. Following stirring at 40 rpm, the cell viability is estimated with trypan blue. In another format, Fibra-Cel microcarriers (Bibby Sterlin, Stone, UK) (5 g/l) is employed as follows. A cell inoculum, resuspended in 5 ml of medium, is added to the carrier (50 ml) in a 250 ml Erlenmeyer flask and left stationary, with occasional agitation, for 1 to 4 h. The medium is then replaced with 50 ml of fresh medium and shaking initiated. For virus production, cells are allowed to grow to about 80% confluence, after which time the medium is replaced (to 25% of the final volume) and adenovirus added at an MOI of 0.05. Cultures are left stationary overnight, following which the volume is increased to 100% and shaking commenced for another 72 h.

Other than the requirement that the adenovirus vector be replication defective, or at least conditionally defective, the nature of the adenovirus vector is not believed to be crucial to the successful practice of the invention. The adenovirus may be of any of the 42 different known serotypes or subgroups A-F. Adenovirus type 5 of subgroup C is the preferred starting material in order to obtain a conditional replication-defective adenovirus vector for use in the present invention, since Adenovirus type 5 is a human adenovirus about which a great deal of biochemical and genetic information is known, and it has historically been used for most constructions employing adenovirus as a vector.

As stated above, the typical vector according to the present invention is replication defective and will not have an adenovirus E1 region. Thus, it will be most convenient to introduce the polynucleotide encoding the gene of interest at the position from which the E1-coding sequences have been removed. However, the position of insertion of the construct within the adenovirus sequences is not critical to the invention. The polynucleotide encoding the gene of interest may also be inserted in lieu of the deleted E3 region in E3 replacement vectors as described by Karlsson et al. (1986) or in the E4 region where a helper cell line or helper virus complements the E4 defect.

Adenovirus is easy to grow and manipulate and exhibits broad host range in vitro and in vivo. This group of viruses can be obtained in high titers, e.g., 10 ⁹-10¹¹plaque-forming units per ml, and they are highly infective. The life cycle of adenovirus does not require integration into the host cell genome. The foreign genes delivered by adenovirus vectors are episomal and, therefore, have low genotoxicity to host cells. No side effects have been reported in studies of vaccination with wild-type adenovirus (Couch et al., 1963; Top et al., 1971), demonstrating their safety and therapeutic potential as in vivo gene transfer vectors.

Adenovirus vectors have been used in eukaryotic gene expression (Levrero et al., 1991; Gomez-Foix et al., 1992) and vaccine development (Grunhaus and Horwitz, 1992; Graham and Prevec, 1992). Recently, animal studies suggested that recombinant adenovirus could be used for gene therapy (Stratford-Perricaudet and Perricaudet, 1991; Stratford-Perricaudet et al., 1990; Rich et al., 1993). Studies in administering recombinant adenovirus to different tissues include trachea instillation (Rosenfeld et al., 1991; Rosenfeld et al., 1992), muscle injection (Ragot et al., 1993), peripheral intravenous injections (Herz and Gerard, 1993) and stereotactic inoculation into the brain (Le Gal La Salle et al., 1993).

2. Retroviruses

The retroviruses are a group of single-stranded RNA viruses characterized by an ability to convert their RNA to double-stranded DNA in infected cells by a process of reverse-transcription (Coffin, 1990). The resulting DNA then stably integrates into cellular chromosomes as a provirus and directs synthesis of viral proteins. The integration results in the retention of the viral gene sequences in the recipient cell and its descendants. The retroviral genome contains three genes, gag, pol, and env that code for capsid proteins, polymerase enzyme, and envelope components, respectively. A sequence found upstream from the gag gene contains a signal for packaging of the genome into virions. Two long terminal repeat (LTR) sequences are present at the 5′ and 3′ ends of the viral genome. These contain strong promoter and enhancer sequences and are also required for integration in the host cell genome (Coffin, 1990).

In order to construct a retroviral vector, a nucleic acid encoding one or more oligonucleotide or polynucleotide sequences of interest is inserted into the viral genome in the place of certain viral sequences to produce a virus that is replication-defective. In order to produce virions, a packaging cell line containing the gag, pol, and env genes but without the LTR and packaging components is constructed (Mann et al., 1983). When a recombinant plasmid containing a cDNA, together with the retroviral LTR and packaging sequences is introduced into this cell line (by calcium phosphate precipitation for example), the packaging sequence allows the RNA transcript of the recombinant plasmid to be packaged into viral particles, which are then secreted into the culture media (Nicolas and Rubenstein, 1988; Temin, 1986; Mann et al, 1983). The media containing the recombinant retroviruses is then collected, optionally concentrated, and used for gene transfer. Retroviral vectors are able to infect a broad variety of cell types. However, integration and stable expression require the division of host cells (Paskind et al., 1975).

A novel approach designed to allow specific targeting of retrovirus vectors was recently developed based on the chemical modification of a retrovirus by the chemical addition of lactose residues to the viral envelope. This modification could permit the specific infection of hepatocytes via sialoglycoprotein receptors.

A different approach to targeting of recombinant retroviruses was designed in which biotinylated antibodies against a retroviral envelope protein and against a specific cell receptor were used. The antibodies were coupled via the biotin components by using streptavidin (Roux et al., 1989). Using antibodies against major histocompatibility complex class I and class II antigens, they demonstrated the infection of a variety of human cells that bore those surface antigens with an ecotropic virus in vitro (Roux et al., 1989).

3. Adeno-Associated Viruses

AAV (Ridgeway, 1988; Hermonat and Muzycska, 1984) is a parovirus, discovered as a contamination of adenoviral stocks. It is a ubiquitous virus (antibodies are present in 85% of the US human population) that has not been linked to any disease. It is also classified as a dependovirus, because its replications is dependent on the presence of a helper virus, such as adenovirus. Five serotypes have been isolated, of which AAV-2 is the best characterized. AAV has a single-stranded linear DNA that is encapsidated into capsid proteins VP1, VP2 and VP3 to form an icosahedral virion of 20 to 24 nm in diameter (Muzyczka and McLaughlin, 1988).

The AAV DNA is approximately 4.7 kilobases long. It contains two open reading frames and is flanked by two ITRs (FIG. 2). There are two major genes in the AAV genome: rep and cap. The rep gene codes for proteins responsible for viral replications, whereas cap codes for capsid protein VP1-3. Each ITR forms a T-shaped hairpin structure. These terminal repeats are the only essential cis components of the AAV for chromosomal integration. Therefore, the AAV can be used as a vector with all viral coding sequences removed and replaced by the cassette of genes for delivery. Three viral promoters have been identified and named p5, p19, and p40, according to their map position. Transcription from p5 and p19 results in production of rep proteins, and transcription from p40 produces the capsid proteins (Hermonat and Muzyczka, 1984).

There are several factors that prompted researchers to study the possibility of using rAAV as an expression vector One is that the requirements for delivering a gene to integrate into the host chromosome are surprisingly few. It is necessary to have the 145-bp ITRs, which are only 6% of the AAV genome. This leaves room in the vector to assemble a 4.5-kb DNA insertion. While this carrying capacity may prevent the AAV from delivering large genes, it is amply suited for delivering the antisense constructs of the present invention.

AAV is also a good choice of delivery vehicles due to its safety. There is a relatively complicated rescue mechanism: not only wild type adenovirus but also AAV genes are required to mobilize rAAV. Likewise, AAV is not pathogenic and not associated with any disease. The removal of viral coding sequences minimizes immune reactions to viral gene expression, and therefore, rAAV does not evoke an inflammatory response.

4. Other Viral Vectors as Expression Constructs

Other viral vectors may be employed as expression constructs in the present invention for the delivery of oligonucleotide or polynucleotide sequences to a host cell. Vectors derived from viruses such as vaccinia virus (Ridgeway, 1988; Coupar et al., 1988), lentiviruses, polio viruses and herpes viruses may be employed. They offer several attractive features for various mammalian cells (Friedmann, 1989; Ridgeway, 1988; Coupar et al., 1988; Horwich et al., 1990).

With the recent recognition of defective hepatitis B viruses, new insight was gained into the structure-function relationship of different viral sequences. In vitro studies showed that the virus could retain the ability for helper-dependent packaging and reverse transcription despite the deletion of up to 80% of its genome (Horwich et al, 1990). This suggested that large portions of the genome could be replaced with foreign genetic material. The hepatotropism and persistence (integration) were particularly attractive properties for liver-directed gene transfer. Chang et al. (1991) introduced the chloramphenicol acetyltransferase (CAT) gene into duck hepatitis B virus genome in the place of the polymerase, surface, and pre-surface coding sequences. It was cotransfected with wild-type virus into an avian hepatoma cell line. Culture media containing high titers of the recombinant virus were used to infect primary duckling hepatocytes. Stable CAT gene expression was detected for at least 24 days after transfection (Chang et al., 1991).

5. Non-Viral Vectors

In order to effect expression of the oligonucleotide or polynucleotide sequences of the present invention, the expression construct must be delivered into a cell. This delivery may be accomplished in vitro, as in laboratory procedures for transforming cells lines, or in vivo or ex vivo, as in the treatment of certain disease states. As described above, one preferred mechanism for delivery is via viral infection where the expression construct is encapsulated in an infectious viral particle.

Once the expression construct has been delivered into the cell the nucleic acid encoding the desired oligonucleotide or polynucleotide sequences may be positioned and expressed at different sites. In certain embodiments, the nucleic acid encoding the construct may be stably integrated into the genome of the cell. This integration may be in the specific location and orientation via homologous recombination (gene replacement) or it may be integrated in a random, non-specific location (gene augmentation). In yet further embodiments, the nucleic acid may be stably maintained in the cell as a separate, episomal segment of DNA. Such nucleic acid segments or “episomes” encode sequences sufficient to permit maintenance and replication independent of or in synchronization with the host cell cycle. How the expression construct is delivered to a cell and where in the cell the nucleic acid remains is dependent on the type of expression construct employed.

In certain embodiments of the invention, the expression construct comprising one or more oligonucleotide or polynucleotide sequences may simply consist of naked recombinant DNA or plasmids. Transfer of the construct may be performed by any of the methods mentioned above which physically or chemically permeabilize the cell membrane. This is particularly applicable for transfer in vitro but it may be applied to in vivo use as well. Dubensky et al. (1984) successfully injected polyomavirus DNA in the form of calcium phosphate precipitates into liver and spleen of adult and newborn mice demonstrating active viral replication and acute infection. Benvenisty and Reshef (1986) also demonstrated that direct intraperitoneal injection of calcium phosphate-precipitated plasmids results in expression of the transfected genes. It is envisioned that DNA encoding a gene of interest may also be transferred in a similar manner in vivo and express the gene product.

Another embodiment of the invention for transferring a naked DNA expression construct into cells may involve particle bombardment. This method depends on the ability to accelerate DNA-coated microprojectiles to a high velocity allowing them to pierce cell membranes and enter cells without killing them (Klein et al., 1987). Several devices for accelerating small particles have been developed. One such device relies on a high voltage discharge to generate an electrical current, which in turn provides the motive force (Yang et al., 1990). The microprojectiles used have consisted of biologically inert substances such as tungsten or gold beads.

Selected organs including the liver, skin, and muscle tissue of rats and mice have been bombarded in vivo (Yang et al., 1990; Zelenin et al., 1991). This may require surgical exposure of the tissue or cells, to eliminate any intervening tissue between the gun and the target organ, i.e. ex vivo treatment. Again, DNA encoding a particular gene may be delivered via this method and still be incorporated by the present invention.

Antisense Oligonucleotides

The end result of the flow of genetic information is the synthesis of protein. DNA is transcribed by polymerases into messenger RNA and translated on the ribosome to yield a folded, functional protein. Thus there are several steps along the route where protein synthesis can be inhibited. The native DNA segment coding for a polypeptide described herein, as all such mammalian DNA strands, has two strands: a sense strand and an antisense strand held together by hydrogen bonding. The messenger RNA coding for polypeptide has the same nucleotide sequence as the sense DNA strand except that the DNA thymidine is replaced by uridine. Thus, synthetic antisense nucleotide sequences will bind to a mRNA and inhibit expression of the protein encoded by that mRNA.

The targeting of antisense oligonucleotides to mRNA is thus one mechanism to shut down protein synthesis, and, consequently, represents a powerful and targeted therapeutic approach. For example, the synthesis of polygalactauronase and the muscarine type 2 acetylcholine receptor are inhibited by antisense oligonucleotides directed to their respective mRNA sequences (U.S. Pat. No. 5,739,119 and U.S. Pat. No. 5,759,829, each specifically incorporated herein by reference in its entirety). Further, examples of antisense inhibition have been demonstrated with the nuclear protein cyclin, the multiple drug resistance gene (MDG1), ICAM-1, E-selectin, STK-1, striatal GABA _Areceptor and human EGF (Jaskulski et al., 1988; Vasanthakumar and Ahmed, 1989; Peris et al., 1998; U.S. Pat. No. 5,801,154; U.S. Pat. No. 5,789,573; U.S. Pat. No. 5,718,709 and U.S. Pat. No. 5,610,288, each specifically incorporated herein by reference in its entirety). Antisense constructs have also been described that inhibit and can be used to treat a variety of abnormal cellular proliferations, e.g. cancer (U.S. Pat. No. 5,747,470; U.S. Pat. No. 5,591,317 and U.S. Pat. No. 5,783,683, each specifically incorporated herein by reference in its entirety).

Therefore, in exemplary embodiments, the invention provides oligonucleotide sequences that comprise all, or a portion of, any sequence that is capable of specifically binding to polynucleotide sequence described herein, or a complement thereof. In one embodiment, the antisense oligonucleotides comprise DNA or derivatives thereof. In another embodiment, the oligonucleotides comprise RNA or derivatives thereof. In a third embodiment, the oligonucleotides are modified DNAs comprising a phosphorothioated modified backbone. In a fourth embodiment, the oligonucleotide sequences comprise peptide nucleic acids or derivatives thereof. In each case, preferred compositions comprise a sequence region that is complementary, and more preferably substantially-complementary, and even more preferably, completely complementary to one or more portions of polynucleotides disclosed herein.

Selection of antisense compositions specific for a given gene sequence is based upon analysis of the chosen target sequence (i.e. in these illustrative examples the rat and human sequences) and determination of secondary structure, T _m, binding energy, relative stability, and antisense compositions were selected based upon their relative inability to form dimers, hairpins, or other secondary structures that would reduce or prohibit specific binding to the target mRNA in a host cell.

Highly preferred target regions of the mRNA, are those which are at or near the AUG translation initiation codon, and those sequences which were substantially complementary to 5′ regions of the mRNA. These secondary structure analyses and target site selection considerations were performed using v.4 of the OLIGO primer analysis software (Rychlik, 1997) and the BLASTN 2.0.5 algorithm software (Altschul et al., 1997).

The use of an antisense delivery method employing a short peptide vector, termed MPG (27 residues), is also contemplated. The MPG peptide contains a hydrophobic domain derived from the fusion sequence of HIV gp41 and a hydrophilic domain from the nuclear localization sequence of SV40 T-antigen (Morris et al., 1997). It has been demonstrated that several molecules of the MPG peptide coat the antisense oligonucleotides and can be delivered into cultured mammalian cells in less than 1 hour with relatively high efficiency (90%). Further, the interaction with MPG strongly increases both the stability of the oligonucleotide to nuclease and the ability to cross the plasma membrane (Morris et al., 1997).

Ribozymes

Although proteins traditionally have been used for catalysis of nucleic acids, another class of macromolecules has emerged as useful in this endeavor. Ribozymes are RNA-protein complexes that cleave nucleic acids in a site-specific fashion. Ribozymes have specific catalytic domains that possess endonuclease activity (Kim and Cech, 1987; Gerlach et al., 1987; Forster and Symons, 1987). For example, a large number of ribozymes accelerate phosphoester transfer reactions with a high degree of specificity, often cleaving only one of several phosphoesters in an oligonucleotide substrate (Cech et al., 1981; Michel and Westhof, 1990; Reinhold-Hurek and Shub, 1992). This specificity has been attributed to the requirement that the substrate bind via specific base-pairing interactions to the internal guide sequence (“IGS”) of the ribozyme prior to chemical reaction.

Ribozyme catalysis has primarily been observed as part of sequence-specific cleavage/ligation reactions involving nucleic acids (Joyce, 1989; Cech et al., 1981). For example, U.S. Pat. No. 5,354,855 (specifically incorporated herein by reference) reports that certain ribozymes can act as endonucleases with a sequence specificity greater than that of known ribonucleases and approaching that of the DNA restriction enzymes. Thus, sequence-specific ribozyme-mediated inhibition of gene expression may be particularly suited to therapeutic applications (Scanlon et al., 1991; Sarver et al, 1990). Recently, it was reported that ribozymes elicited genetic changes in some cells lines to which they were applied; the altered genes included the oncogenes H-ras, c-fos and genes of HIV. Most of this work involved the modification of a target mRNA, based on a specific mutant codon that is cleaved by a specific ribozyme.

Six basic varieties of naturally-occurring enzymatic RNAs are known presently. Each can catalyze the hydrolysis of RNA phosphodiester bonds in trans (and thus can cleave other RNA molecules) under physiological conditions. In general, enzymatic nucleic acids act by first binding to a target RNA. Such binding occurs through the target binding portion of a enzymatic nucleic acid which is held in close proximity to an enzymatic portion of the molecule that acts to cleave the target RNA. Thus, the enzymatic nucleic acid first recognizes and then binds a target RNA through complementary base-pairing, and once bound to the correct site, acts enzymatically to cut the target RNA. Strategic cleavage of such a target RNA will destroy its ability to direct synthesis of an encoded protein. After an enzymatic nucleic acid has bound and cleaved its RNA target, it is released from that RNA to search for another target and can repeatedly bind and cleave new targets.

The enzymatic nature of a ribozyme is advantageous over many technologies, such as antisense technology (where a nucleic acid molecule simply binds to a nucleic acid target to block its translation) since the concentration of ribozyme necessary to affect a therapeutic treatment is lower than that of an antisense oligonucleotide. This advantage reflects the ability of the ribozyme to act enzymatically. Thus, a single ribozyme molecule is able to cleave many molecules of target RNA. In addition, the ribozyme is a highly specific inhibitor, with the specificity of inhibition depending not only on the base pairing mechanism of binding to the target RNA, but also on the mechanism of target RNA cleavage. Single mismatches, or base-substitutions, near the site of cleavage can completely eliminate catalytic activity of a ribozyme. Similar mismatches in antisense molecules do not prevent their action (Woolf et al., 1992). Thus, the specificity of action of a ribozyme is greater than that of an antisense oligonucleotide binding the same RNA site.

The enzymatic nucleic acid molecule may be formed in a hammerhead, hairpin, a hepatitis 6 virus, group I intron or RNaseP RNA (in association with an RNA guide sequence) or Neurospora VS RNA motif. Examples of hammerhead motifs are described by Rossi et al. (1992). Examples of hairpin motifs are described by Hampel et al. (Eur. Pat. Appl. Publ. No. EP 0360257), Hampel and Tritz (1989), Hampel et al. (1990) and U.S. Pat. No. 5,631,359 (specifically incorporated herein by reference). An example of the hepatitis δ virus motif is described by Perrotta and Been (1992); an example of the RNaseP motif is described by Guerrier-Takada et al. (1983); Neurospora VS RNA ribozyme motif is described by Collins (Saville and Collins, 1990; Saville and Collins, 1991; Collins and Olive, 1993); and an example of the Group I intron is described in (U.S. Pat. No. 4,987,071, specifically incorporated herein by reference). All that is important in an enzymatic nucleic acid molecule of this invention is that it has a specific substrate binding site which is complementary to one or more of the target gene RNA regions, and that it have nucleotide sequences within or surrounding that substrate binding site which impart an RNA cleaving activity to the molecule. Thus the ribozyme constructs need not be limited to specific motifs mentioned herein.

In certain embodiments, it may be important to produce enzymatic cleaving agents which exhibit a high degree of specificity for the RNA of a desired target, such as one of the sequences disclosed herein. The enzymatic nucleic acid molecule is preferably targeted to a highly conserved sequence region of a target mRNA. Such enzymatic nucleic acid molecules can be delivered exogenously to specific cells as required. Alternatively, the ribozymes can be expressed from DNA or RNA vectors that are delivered to specific cells.

Small enzymatic nucleic acid motifs (e.g., of the hammerhead or the hairpin structure) may also be used for exogenous delivery. The simple structure of these molecules increases the ability of the enzymatic nucleic acid to invade targeted regions of the mRNA structure. Alternatively, catalytic RNA molecules can be expressed within cells from eukaryotic promoters (e.g., Scanlon et al., 1991; Kashani-Sabet et al., 1992; Dropulic et al., 1992; Weerasinghe et al., 1991; Ojwang et al., 1992; Chen et al., 1992; Sarver et al., 1990). Those skilled in the art realize that any ribozyme can be expressed in eukaryotic cells from the appropriate DNA vector. The activity of such ribozymes can be augmented by their release from the primary transcript by a second ribozyme (Int. Pat. Appl. Publ. No. WO 93/23569, and Int. Pat. Appl. Publ. No. WO 94/02595, both hereby incorporated by reference; Ohkawa et al., 1992; Taira et al., 1991; and Ventura et al., 1993).

Ribozymes may be added directly, or can be complexed with cationic lipids, lipid complexes, packaged within liposomes, or otherwise delivered to target cells. The RNA or RNA complexes can be locally administered to relevant tissues ex vivo, or in vivo through injection, aerosol inhalation, infusion pump or stent, with or without their incorporation in biopolymers.

Ribozymes may be designed as described in Int. Pat. Appl. Publ. No. WO 93/23569 and Int. Pat. Appl. Publ. No. WO 94/02595, each specifically incorporated herein by reference) and synthesized to be tested in vitro and in vivo, as described. Such ribozymes can also be optimized for delivery. While specific examples are provided, those in the art will recognize that equivalent RNA targets in other species can be utilized when necessary.

Hammerhead or hairpin ribozymes may be individually analyzed by computer folding (Jaeger et al., 1989) to assess whether the ribozyme sequences fold into the appropriate secondary structure. Those ribozymes with unfavorable intramolecular interactions between the binding arms and the catalytic core are eliminated from consideration. Varying binding arm lengths can be chosen to optimize activity. Generally, at least 5 or so bases on each arm are able to bind to, or otherwise interact with, the target RNA.

Ribozymes of the hammerhead or hairpin motif may be designed to anneal to various sites in the mRNA message, and can be chemically synthesized. The method of synthesis used follows the procedure for normal RNA synthesis as described in Usman et al. (1987) and in Scaringe et al. (1990) and makes use of common nucleic acid protecting and coupling groups, such as dimethoxytrityl at the 5′-end, and phosphoramidites at the 3′-end. Average stepwise coupling yields are typically >98%. Hairpin ribozymes may be synthesized in two parts and annealed to reconstruct an active ribozyme (Chowrira and Burke, 1992). Ribozymes may be modified extensively to enhance stability by modification with nuclease resistant groups, for example, 2′-amino, 2′-C-allyl, 2′-flouro, 2′-o-methyl, 2′-H (for a review see e.g., Usman and Cedergren, 1992). Ribozymes may be purified by gel electrophoresis using general methods or by high pressure liquid chromatography and resuspended in water.

Ribozyme activity can be optimized by altering the length of the ribozyme binding arms, or chemically synthesizing ribozymes with modifications that prevent their degradation by serum ribonucleases (see e.g., Int. Pat. Appl. Publ. No. WO 92/07065; Perrault et al, 1990; Pieken et al., 1991; Usman and Cedergren, 1992; Int. Pat. Appl. Publ. No. WO 93/15187; Int. Pat. Appl. Publ. No. WO 91/03162; Eur. Pat. Appl. Publ. No. 92110298.4; U.S. Pat. No. 5,334,711; and Int. Pat. Appl. Publ. No. WO 94/13688, which describe various chemical modifications that can be made to the sugar moieties of enzymatic RNA molecules), modifications which enhance their efficacy in cells, and removal of stem II bases to shorten RNA synthesis times and reduce chemical requirements.

Sullivan et al. (Int. Pat. Appl. Publ. No. WO 94/02595) describes the general methods for delivery of enzymatic RNA molecules. Ribozymes may be administered to cells by a variety of methods known to those familiar to the art, including, but not restricted to, encapsulation in liposomes, by iontophoresis, or by incorporation into other vehicles, such as hydrogels, cyclodextrins, biodegradable nanocapsules, and bioadhesive microspheres. For some indications, ribozymes may be directly delivered ex vivo to cells or tissues with or without the aforementioned vehicles. Alternatively, the RNA/vehicle combination may be locally delivered by direct inhalation, by direct injection or by use of a catheter, infusion pump or stent. Other routes of delivery include, but are not limited to, intravascular, intramuscular, subcutaneous or joint injection, aerosol inhalation, oral (tablet or pill form), topical, systemic, ocular, intraperitoneal and/or intrathecal delivery. More detailed descriptions of ribozyme delivery and administration are provided in Int. Pat. Appl. Publ. No. WO 94/02595 and Int. Pat. Appl. Publ. No. WO 93/23569, each specifically incorporated herein by reference.

Another means of accumulating high concentrations of a ribozyme(s) within cells is to incorporate the ribozyme-encoding sequences into a DNA expression vector. Transcription of the ribozyme sequences are driven from a promoter for eukaryotic RNA polymerase I (pol I), RNA polymerase II (pol II), or RNA polymerase III (pol III). Transcripts from pol II or pol III promoters will be expressed at high levels in all cells; the levels of a given pol II promoter in a given cell type will depend on the nature of the gene regulatory sequences (enhancers, silencers, etc.) present nearby. Prokaryotic RNA polymerase promoters may also be used, providing that the prokaryotic RNA polymerase enzyme is expressed in the appropriate cells (Elroy-Stein and Moss, 1990; Gao and Huang, 1993; Lieber et al.., 1993; Zhou et al., 1990). Ribozymes expressed from such promoters can function in mammalian cells (e.g. Kashani-Saber et al., 1992; Ojwang et al., 1992; Chen et al., 1992; Yu et al., 1993; L'Huillier et al., 1992; Lisziewicz et al., 1993). Such transcription units can be incorporated into a variety of vectors for introduction into mammalian cells, including but not restricted to, plasmid DNA vectors, viral DNA vectors (such as adenovirus or adeno-associated vectors), or viral RNA vectors (such as retroviral, semliki forest virus, sindbis virus vectors).

Ribozymes may be used as diagnostic tools to examine genetic drift and mutations within diseased cells. They can also be used to assess levels of the target RNA molecule. The close relationship between ribozyme activity and the structure of the target RNA allows the detection of mutations in any region of the molecule which alters the base-pairing and three-dimensional structure of the target RNA. By using multiple ribozymes, one may map nucleotide changes which are important to RNA structure and function in vitro, as well as in cells and tissues. Cleavage of target RNAs with ribozymes may be used to inhibit gene expression and define the role (essentially) of specified gene products in the progression of disease. In this manner, other genetic targets may be defined as important mediators of the disease. These studies will lead to better treatment of the disease progression by affording the possibility of combinational therapies (e.g., multiple ribozymes targeted to different genes, ribozymes coupled with known small molecule inhibitors, or intermittent treatment with combinations of ribozymes and/or other chemical or biological molecules). Other in vitro uses of ribozymes are well known in the art, and include detection of the presence of mRNA associated with an IL-5 related condition. Such RNA is detected by determining the presence of a cleavage product after treatment with a ribozyme using standard methodology.

Peptide Nucleic Acids

In certain embodiments, the inventors contemplate the use of peptide nucleic acids (PNAs) in the practice of the methods of the invention. PNA is a DNA mimic in which the nucleobases are attached to a pseudopeptide backbone (Good and Nielsen, 1997). PNA is able to be utilized in a number methods that traditionally have used RNA or DNA. Often PNA sequences perform better in techniques than the corresponding RNA or DNA sequences and have utilities that are not inherent to RNA or DNA. A review of PNA including methods of making, characteristics of, and methods of using, is provided by Corey (1997) and is incorporated herein by reference. As such, in certain embodiments, one may prepare PNA sequences that are complementary to one or more portions of the ACE mRNA sequence, and such PNA compositions may be used to regulate, alter, decrease, or reduce the translation of ACE-specific mRNA, and thereby alter the level of ACE activity in a host cell to which such PNA compositions have been administered.

PNAs have 2-aminoethyl-glycine linkages replacing the normal phosphodiester backbone of DNA (Nielsen et al.., 1991; Hanvey et al., 1992; Hyrup and Nielsen, 1996; Neilsen, 1996). This chemistry has three important consequences: firstly, in contrast to DNA or phosphorothioate oligonucleotides, PNAs are neutral molecules; secondly, PNAs are achiral, which avoids the need to develop a stereoselective synthesis; and thirdly, PNA synthesis uses standard Boc (Dueholm et al., 1994) or Fmoc (Thomson et al., 1995) protocols for solid-phase peptide synthesis, although other methods, including a modified Merrifield method, have been used (Christensen et al., 1995).

PNA monomers or ready-made oligomers are commercially available from PerSeptive Biosystems (Framingham, Mass.). PNA syntheses by either Boc or Fmoc protocols are straightforward using manual or automated protocols (Norton et al., 1995). The manual protocol lends itself to the production of chemically modified PNAs or the simultaneous synthesis of families of closely related PNAs.

As with peptide synthesis, the success of a particular PNA synthesis will depend on the properties of the chosen sequence. For example, while in theory PNAs can incorporate any combination of nucleotide bases, the presence of adjacent purines can lead to deletions of one or more residues in the product. In expectation of this difficulty, it is suggested that, in producing PNAs with adjacent purines, one should repeat the coupling of residues likely to be added inefficiently. This should be followed by the purification of PNAs by reverse-phase high-pressure liquid chromatography (Norton et al., 1995) providing yields and purity of product similar to those observed during the synthesis of peptides.

Modifications of PNAs for a given application may be accomplished by coupling amino acids during solid-phase synthesis or by attaching compounds that contain a carboxylic acid group to the exposed N-terminal amine. Alternatively, PNAs can be modified after synthesis by coupling to an introduced lysine or cysteine. The ease with which PNAs can be modified facilitates optimization for better solubility or for specific functional requirements. Once synthesized, the identity of PNAs and their derivatives can be confirmed by mass spectrometry. Several studies have made and utilized modifications of PNAs (Norton et al., 1995; Haaima et al., 1996; Stetsenko et al., 1996; Petersen et al., 1995; Ulmann et al., 1996; Koch et al., 1995; Orum et al., 1995; Footer et al., 1996; Griffith et al., 1995; Kremsky et al., 1996; Pardridge et al., 1995; Boffa et al., 1995; Landsdorp et al., 1996; Gambacorti-Passerini et al., 1996; Armitage et al., 1997; Seeger et al., 1997; Ruskowski et al, 1997). U.S. Pat. No. 5,700,922 discusses PNA-DNA-PNA chimeric molecules and their uses in diagnostics, modulating protein in organisms, and treatment of conditions susceptible to therapeutics.

In contrast to DNA and RNA, which contain negatively charged linkages, the PNA backbone is neutral. In spite of this dramatic alteration, PNAs recognize complementary DNA and RNA by Watson-Crick pairing (Egholm et al., 1993), validating the initial modeling by Nielsen et al. (1991). PNAs lack 3′ to 5′ polarity and can bind in either parallel or antiparallel fashion, with the antiparallel mode being preferred (Egholm et al., 1993).

Hybridization of DNA oligonucleotides to DNA and RNA is destabilized by electrostatic repulsion between the negatively charged phosphate backbones of the complementary strands. By contrast, the absence of charge repulsion in PNA-DNA or PNA-RNA duplexes increases the melting temperature (T _m) and reduces the dependence of T_mon the concentration of mono- or divalent cations (Nielsen et al., 1991). The enhanced rate and affinity of hybridization are significant because they are responsible for the surprising ability of PNAs to perform strand invasion of complementary sequences within relaxed double-stranded DNA. In addition, the efficient hybridization at inverted repeats suggests that PNAs can recognize secondary structure effectively within double-stranded DNA. Enhanced recognition also occurs with PNAs immobilized on surfaces, and Wang et al. have shown that support-bound PNAs can be used to detect hybridization events (Wang et al., 1996).

One might expect that tight binding of PNAs to complementary sequences would also increase binding to similar (but not identical) sequences, reducing the sequence specificity of PNA recognition. As with DNA hybridization, however, selective recognition can be achieved by balancing oligomer length and incubation temperature. Moreover, selective hybridization of PNAs is encouraged by PNA-DNA hybridization being less tolerant of base mismatches than DNA-DNA hybridization. For example, a single mismatch within a 16 bp PNA-DNA duplex can reduce the T _mby up to 15° C. (Egholm et al., 1993). This high level of discrimination has allowed the development of several PNA-based strategies for the analysis of point mutations (Wang et al., 1996; Carlsson et al., 1996; Thiede et al., 1996; Webb and Hurskainen, 1996; Perry-O'Keefe et al., 1996).

High-affinity binding provides clear advantages for molecular recognition and the development of new applications for PNAs. For example, 11-13 nucleotide PNAs inhibit the activity of telomerase, a ribonucleo-protein that extends telomere ends using an essential RNA template, while the analogous DNA oligomers do not (Norton et al., 1996).

Neutral PNAs are more hydrophobic than analogous DNA oligomers, and this can lead to difficulty solubilizing them at neutral pH, especially if the PNAs have a high purine content or if they have the potential to form secondary structures. Their solubility can be enhanced by attaching one or more positive charges to the PNA termini (Nielsen et al., 1991).

Findings by Allfrey and colleagues suggest that strand invasion will occur spontaneously at sequences within chromosomal DNA (Boffa et al., 1995; Boffa et al., 1996). These studies targeted PNAs to triplet repeats of the nucleotides CAG and used this recognition to purify transcriptionally active DNA (Boffa et al., 1995) and to inhibit transcription (Boffa et al., 1996). This result suggests that if PNAs can be delivered within cells then they will have the potential to be general sequence-specific regulators of gene expression. Studies and reviews concerning the use of PNAs as antisense and anti-gene agents include Nielsen et al. (1993b), Hanvey et al. (1992), and Good and Nielsen (1997). Koppelhus et al. (1997) have used PNAs to inhibit HIV-1 inverse transcription, showing that PNAs may be used for antiviral therapies.

Methods of characterizing the antisense binding properties of PNAs are discussed in Rose (1993) and Jensen et al. (1997). Rose uses capillary gel electrophoresis to determine binding of PNAs to their complementary oligonucleotide, measuring the relative binding kinetics and stoichiometry. Similar types of measurements were made by Jensen et al. using BIAcore™ technology.

Other applications of PNAs include use in DNA strand invasion (Nielsen et al., 1991), antisense inhibition (Hanvey et al., 1992), mutational analysis (Orum et al., 1993), enhancers of transcription (Mollegaard et al., 1994), nucleic acid purification (Orum et al., 1995), isolation of transcriptionally active genes (Boffa et al., 1995), blocking of transcription factor binding (Vickers et al., 1995), genome cleavage (Veselkov et al., 1996), biosensors (Wang et al., 1996), in situ hybridization (Thisted et al., 1996), and in a alternative to Southern blotting (Perry-O'Keefe, 1996).

Polypeptide Compositions and Uses

The present invention, in other aspects, provides polypeptide compositions. Generally, a polypeptide of the invention will be an isolated polypeptide (or an epitope, variant, or active fragment thereof) derived from a mammalian species. Preferably, the polypeptide is encoded by a polynucleotide sequence disclosed herein or a sequence which hybridizes under moderately stringent conditions to a polynucleotide sequence disclosed herein. Alternatively, the polypeptide may be defined as a polypeptide which comprises a contiguous amino acid sequence from an amino acid sequence disclosed herein, or which polypeptide comprises an entire amino acid sequence disclosed herein.

Likewise, a polypeptide composition of the present invention is understood to comprise one or more polypeptides that are capable of eliciting antibodies that are immunologically reactive with one or more polypeptides encoded by one or more contiguous nucleic acid sequences contained in SEQ ID NO: 1-48, 114-121, and 125-138, or to active fragments, or to variants thereof, or to one or more nucleic acid sequences which hybridize to one or more of these sequences under conditions of moderate to high stringency.

As used herein, an active fragment of a polypeptide includes a whole or a portion of a polypeptide which is modified by conventional techniques, e.g., mutagenesis, or by addition, deletion, or substitution, but which active fragment exhibits substantially the same structure function, antigenicity, etc., as a polypeptide as described herein.

In certain illustrative embodiments, the polypeptides of the invention will comprise at least an immunogenic portion of a Chlamydia protein or a variant thereof, as described herein. Proteins that are Chlamydia proteins generally also react detectably within an immunoassay (such as an ELISA) with antisera from a patient with a Chlamydial infection. Polypeptides as described herein may be of any length. Additional sequences derived from the native protein and/or heterologous sequences may be present, and such sequences may (but need not) possess further immunogenic or antigenic properties.

An “immunogenic portion,” as used herein is a portion of a protein that is recognized (i.e., specifically bound) by a B-cell and/or T-cell surface antigen receptor. Such immunogenic portions generally comprise at least 5 amino acid residues, more preferably at least 10, and still more preferably at least 20 amino acid residues of a Chlamydia protein or a variant thereof. Certain preferred immunogenic portions include peptides in which an N-terminal leader sequence and/or transmembrane domain have been deleted. Other preferred immunogenic portions may contain a small N- and/or C-terminal deletion (e.g., 1-30 amino acids, preferably 5-15 amino acids), relative to the mature protein.

Immunogenic portions may generally be identified using well known techniques, such as those summarized in Paul, Fundamental Immunology, 3rd ed., 243-247 (Raven Press, 1993) and references cited therein. Such techniques include screening polypeptides for the ability to react with antigen-specific antibodies, antisera and/or T-cell lines or clones. As used herein, antisera and antibodies are “antigen-specific” if they specifically bind to an antigen (i.e., they react with the protein in an ELISA or other immunoassay, and do not react detectably with unrelated proteins). Such antisera and antibodies may be prepared as described herein, and using well known techniques. An immunogenic portion of a native Chlamydia protein is a portion that reacts with such antisera and/or T-cells at a level that is not substantially less than the reactivity of the full length polypeptide (e.g., in an ELISA and/or T-cell reactivity assay). Such immunogenic portions may react within such assays at a level that is similar to or greater than the reactivity of the full length polypeptide. Such screens may generally be performed using methods well known to those of ordinary skill in the art, such as those described in Harlow and Lane, Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, 1988. For example, a polypeptide may be immobilized on a solid support and contacted with patient sera to allow binding of antibodies within the sera to the immobilized polypeptide. Unbound sera may then be removed and bound antibodies detected using, for example, ¹²⁵I-labeled Protein A.

As noted above, a composition may comprise a variant of a native Chlamydia protein. A polypeptide “variant,” as used herein, is a polypeptide that differs from a native Chlamydia protein in one or more substitutions, deletions, additions and/or insertions, such that the immunogenicity of the polypeptide is not substantially diminished. In other words, the ability of a variant to react with antigen-specific antisera may be enhanced or unchanged, relative to the native protein, or may be diminished by less than 50%, and preferably less than 20%, relative to the native protein. Such variants may generally be identified by modifying one of the above polypeptide sequences and evaluating the reactivity of the modified polypeptide with antigen-specific antibodies or antisera as described herein. Preferred variants include those in which one or more portions, such as an N-terminal leader sequence or transmembrane domain, have been removed. Other preferred variants include variants in which a small portion (e.g., 1-30 amino acids, preferably 5-15 amino acids) has been removed from the N- and/or C-terminal of the mature protein.

Polypeptide variants encompassed by the present invention include those exhibiting at least about 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity (determined as described above) to the polypeptides disclosed herein.

Preferably, a variant contains conservative substitutions. A “conservative substitution” is one in which an amino acid is substituted for another amino acid that has similar properties, such that one skilled in the art of peptide chemistry would expect the secondary structure and hydropathic nature of the polypeptide to be substantially unchanged. Amino acid substitutions may generally be made on the basis of similarity in polarity, charge, solubility, hydrophobicity, hydrophilicity and/or the amphipathic nature of the residues. For example, negatively charged amino acids include aspartic acid and glutamic acid; positively charged amino acids include lysine and arginine; and amino acids with uncharged polar head groups having similar hydrophilicity values include leucine, isoleucine and valine; glycine and alanine; asparagine and glutamine; and serine, threonine, phenylalanine and tyrosine. Other groups of amino acids that may represent conservative changes include: (1) ala, pro, gly, glu, asp, gln, asn, ser, thr; (2) cys, ser, tyr, thr; (3) val, ile, leu, met, ala, phe; (4) lys, arg, his; and (5) phe, tyr, trp, his. A variant may also, or alternatively, contain nonconservative changes. In a preferred embodiment, variant polypeptides differ from a native sequence by substitution, deletion or addition of five amino acids or fewer. Variants may also (or alternatively) be modified by, for example, the deletion or addition of amino acids that have minimal influence on the immunogenicity, secondary structure and hydropathic nature of the polypeptide.

As noted above, polypeptides may comprise a signal (or leader) sequence at the N-terminal end of the protein, which co-translationally or post-translationally directs transfer of the protein. The polypeptide may also be conjugated to a linker or other sequence for ease of synthesis, purification or identification of the polypeptide (e.g., poly-His), or to enhance binding of the polypeptide to a solid support. For example, a polypeptide may be conjugated to an immunoglobulin Fc region.

Polypeptides may be prepared using any of a variety of well known techniques. Recombinant polypeptides encoded by DNA sequences as described above may be readily prepared from the DNA sequences using any of a variety of expression vectors known to those of ordinary skill in the art. Expression may be achieved in any appropriate host cell that has been transformed or transfected with an expression vector containing a DNA molecule that encodes a recombinant polypeptide. Suitable host cells include prokaryotes, yeast, and higher eukaryotic cells, such as mammalian cells and plant cells. Preferably, the host cells employed are E. coli, yeast or a mammalian cell line such as COS or CHO. Supernatants from suitable host/vector systems which secrete recombinant protein or polypeptide into culture media may be first concentrated using a commercially available filter. Following concentration, the concentrate may be applied to a suitable purification matrix such as an affinity matrix or an ion exchange resin. Finally, one or more reverse phase HPLC steps can be employed to further purify a recombinant polypeptide.

Portions and other variants having less than about 100 amino acids, and generally less than about 50 amino acids, may also be generated by synthetic means, using techniques well known to those of ordinary skill in the art. For example, such polypeptides may be synthesized using any of the commercially available solid-phase techniques, such as the Merrifield solid-phase synthesis method, where amino acids are sequentially added to a growing amino acid chain. See Merrifield, J. Am. Chem. Soc. 85:2149-2146, 1963. Equipment for automated synthesis of polypeptides is commercially available from suppliers such as Perkin Elmer/Applied BioSystems Division (Foster City, Calif.), and may be operated according to the manufacturer's instructions.

Within certain specific embodiments, a polypeptide may be a fusion protein that comprises multiple polypeptides as described herein, or that comprises at least one polypeptide as described herein and an unrelated sequence, such as a known Chlamydia protein. A fusion partner may, for example, assist in providing T helper epitopes (an immunological fusion partner), preferably T helper epitopes recognized by humans, or may assist in expressing the protein (an expression enhancer) at higher yields than the native recombinant protein. Certain preferred fusion partners are both immunological and expression enhancing fusion partners. Other fusion partners may be selected so as to increase the solubility of the protein or to enable the protein to be targeted to desired intracellular compartments. Still further fusion partners include affinity tags, which facilitate purification of the protein.

Fusion proteins may generally be prepared using standard techniques, including chemical conjugation. Preferably, a fusion protein is expressed as a recombinant protein, allowing the production of increased levels, relative to a non-fused protein, in an expression system. Briefly, DNA sequences encoding the polypeptide components may be assembled separately, and ligated into an appropriate expression vector. The 3′ end of the DNA sequence encoding one polypeptide component is ligated, with or without a peptide linker, to the 5′ end of a DNA sequence encoding the second polypeptide component so that the reading frames of the sequences are in phase. This permits translation into a single fusion protein that retains the biological activity of both component polypeptides.

A peptide linker sequence may be employed to separate the first and second polypeptide components by a distance sufficient to ensure that each polypeptide folds into its secondary and tertiary structures. Such a peptide linker sequence is incorporated into the fusion protein using standard techniques well known in the art. Suitable peptide linker sequences may be chosen based on the following factors: (1) their ability to adopt a flexible extended conformation; (2) their inability to adopt a secondary structure that could interact with functional epitopes on the first and second polypeptides; and (3) the lack of hydrophobic or charged residues that might react with the polypeptide functional epitopes. Preferred peptide linker sequences contain Gly, Asn and Ser residues. Other near neutral amino acids, such as Thr and Ala may also be used in the linker sequence. Amino acid sequences which may be usefully employed as linkers include those disclosed in Maratea et al., Gene 40:39-46, 1985; Murphy et al., Proc. Natl. Acad. Sci. USA 83:8258-8262, 1986; U.S. Pat. No.4,935,233 and U.S. Pat. No.4,751,180. The linker sequence may generally be from 1 to about 50 amino acids in length. Linker sequences are not required when the first and second polypeptides have non-essential N-terminal amino acid regions that can be used to separate the functional domains and prevent steric interference.

The ligated DNA sequences are operably linked to suitable transcriptional or translational regulatory elements. The regulatory elements responsible for expression of DNA are located only 5′ to the DNA sequence encoding the first polypeptides. Similarly, stop codons required to end translation and transcription termination signals are only present 3′ to the DNA sequence encoding the second polypeptide.

Fusion proteins are also provided. Such proteins comprise a polypeptide as described herein together with an unrelated immunogenic protein. Preferably the immunogenic protein is capable of eliciting a recall response. Examples of such proteins include tetanus, tuberculosis and hepatitis proteins (see, for example, Stoute et al. New Engl. J. Med., 336:86-91, 1997).

Within preferred embodiments, an immunological fusion partner is derived from protein D, a surface protein of the gram-negative bacterium Haemophilus influenza B (WO 91/18926). Preferably, a protein D derivative comprises approximately the first third of the protein (e.g., the first N-terminal 100-110 amino acids), and a protein D derivative may be lipidated. Within certain preferred embodiments, the first 109 residues of a Lipoprotein D fusion partner is included on the N-terminus to provide the polypeptide with additional exogenous T-cell epitopes and to increase the expression level in E. coli (thus functioning as an expression enhancer). The lipid tail ensures optimal presentation of the antigen to antigen presenting cells. Other fusion partners include the non-structural protein from influenzae virus, NS1 (hemaglutinin). Typically, the N-terminal 81 amino acids are used, although different fragments that include T-helper epitopes may be used.

In another embodiment, the immunological fusion partner is the protein known as LYTA, or a portion thereof (preferably a C-terminal portion). LYTA is derived from Streptococcus pneumoniae, which synthesizes an N-acetyl-L-alanine amidase known as amidase LYTA (encoded by the LytA gene; Gene 43:265-292, 1986). LYTA is an autolysin that specifically degrades certain bonds in the peptidoglycan backbone. The C-terminal domain of the LYTA protein is responsible for the affinity to the choline or to some choline analogues such as DEAE. This property has been exploited for the development of E. coli C-LYTA expressing plasmids useful for expression of fusion proteins. Purification of hybrid proteins containing the C-LYTA fragment at the amino terminus has been described (see Biotechnology 10:795-798, 1992). Within a preferred embodiment, a repeat portion of LYTA may be incorporated into a fusion protein. A repeat portion is found in the C-terminal region starting at residue 178. A particularly preferred repeat portion incorporates residues 188-305.

In general, polypeptides (including fusion proteins) and polynucleotides as described herein are isolated. An “isolated” polypeptide or polynucleotide is one that is removed from its original environment. For example, a naturally-occurring protein is isolated if it is separated from some or all of the coexisting materials in the natural system. Preferably, such polypeptides are at least about 90% pure, more preferably at least about 95% pure and most preferably at least about 99% pure. A polynucleotide is considered to be isolated if, for example, it is cloned into a vector that is not a part of the natural environment.

Illustrative Therapeutic Compositions and Uses

In another aspect, the present invention provides methods for using one or more of the above polypeptides or fusion proteins (or polynucleotides encoding such polypeptides or fusion proteins) to induce protective immunity against Chlamydial infection in a patient. As used herein, a “patient” refers to any warm-blooded animal, preferably a human. A patient may be afflicted with a disease, or may be free of detectable disease and/or infection. In other words, protective immunity may be induced to prevent or treat Chlamydial infection.

In this aspect, the polypeptide, fusion protein or polynucleotide molecule is generally present within a pharmaceutical composition or a vaccine. Pharmaceutical compositions may comprise one or more polypeptides, each of which may contain one or more of the above sequences (or variants thereof), and a physiologically acceptable carrier. Vaccines may comprise one or more of the above polypeptides and an immunostimulant, such as an adjuvant or a liposome (into which the polypeptide is incorporated). Such pharmaceutical compositions and vaccines may also contain other Chlamydia antigens, either incorporated into a combination polypeptide or present within a separate polypeptide.

Alternatively, a vaccine may contain polynucleotides encoding one or more polypeptides or fusion proteins as described above, such that the polypeptide is generated in situ. In such vaccines, the polynucleotides may be present within any of a variety of delivery systems known to those of ordinary skill in the art, including nucleic acid expression systems, bacterial and viral expression systems. Appropriate nucleic acid expression systems contain the necessary polynucleotide sequences for expression in the patient (such as a suitable promoter and terminating signal). Bacterial delivery systems involve the administration of a bacterium (such as Bacillus-Calmette-Guerrin) that expresses an immunogenic portion of the polypeptide on its cell surface. In a preferred embodiment, the polynucleotides may be introduced using a viral expression system (e.g., vaccinia or other pox virus, retrovirus, or adenovirus), which may involve the use of a non-pathogenic (defective) virus. Techniques for incorporating polynucleotides into such expression systems are well known to those of ordinary skill in the art. The polynucleotides may also be administered as “naked” plasmid vectors as described, for example, in Ulmer et al., Science 259:1745-1749, 1993 and reviewed by Cohen, Science 259:1691-1692, 1993.Techniques for incorporating DNA into such vectors are well known to those of ordinary skill in the art. A retroviral vector may additionally transfer or incorporate a gene for a selectable marker (to aid in the identification or selection of transduced cells) and/or a targeting moiety, such as a gene that encodes a ligand for a receptor on a specific target cell, to render the vector target specific. Targeting may also be accomplished using an antibody, by methods known to those of ordinary skill in the art.

Other formulations for therapeutic purposes include colloidal dispersion systems, such as macromolecule complexes, nanocapsules, microspheres, beads, and lipid-based systems including oil-in-water emulsions, micelles, mixed micelles, and liposomes. A preferred colloidal system for use as a delivery vehicle in vitro and in vivo is a liposome (i.e., an artificial membrane vesicle). The uptake of naked polynucleotides may be increased by incorporating the polynucleotides into and/or onto biodegradable beads, which are efficiently transported into the cells. The preparation and use of such systems is well known in the art.

In a related aspect, a polynucleotide vaccine as described above may be administered simultaneously with or sequentially to either a polypeptide of the present invention or a known Chlamydia antigen. For example, administration of polynucleotides encoding a polypeptide of the present invention, either “naked” or in a delivery system as described above, may be followed by administration of an antigen in order to enhance the protective immune effect of the vaccine.

Polypeptides and polynucleotides disclosed herein may also be employed in adoptive immunotherapy for the treatment of Chlamydial infection. Adoptive immunotherapy may be broadly classified into either active or passive immunotherapy. In active immunotherapy, treatment relies on the in vivo stimulation of the endogenous host immune system with the administration of immune response-modifying agents (for example, vaccines, bacterial adjuvants, and/or cytokines).

In passive immunotherapy, treatment involves the delivery of biologic reagents with established immune reactivity (such as effector cells or antibodies) that can directly or indirectly mediate anti-Chlamydia effects and does not necessarily depend on an intact host immune system. Examples of effector cells include T lymphocytes (for example, CD8+ cytotoxic T-lymphocyte, CD4+ T-helper), killer cells (such as Natural Killer cells, lymphokine-activated killer cells), B cells, or antigen presenting cells (such as dendritic cells and macrophages) expressing the disclosed antigens. The polypeptides disclosed herein may also be used to generate antibodies or anti-idiotypic antibodies (as in U.S. Pat. No. 4,918,164), for passive immunotherapy.

The predominant method of procuring adequate numbers of T-cells for adoptive immunotherapy is to grow immune T-cells in vitro. Culture conditions for expanding single antigen-specific T-cells to several billion in number with retention of antigen recognition in vivo are well known in the art. These in vitro culture conditions typically utilize intermittent stimulation with antigen, often in the presence of cytokines, such as IL-2, and non-dividing feeder cells. As noted above, the immunoreactive polypeptides described herein may be used to rapidly expand antigen-specific T cell cultures in order to generate sufficient number of cells for immunotherapy. In particular, antigen-presenting cells, such as dendritic, macrophage, monocyte, fibroblast, or B-cells, may be pulsed with immunoreactive polypeptides, or polynucleotide sequence(s) may be introduced into antigen presenting cells, using a variety of standard techniques well known in the art. For example, antigen presenting cells may be transfected or transduced with a polynucleotide sequence, wherein said sequence contains a promoter region appropriate for increasing expression, and can be expressed as part of a recombinant virus or other expression system. Several viral vectors may be used to transduce an antigen presenting cell, including pox virus, vaccinia virus, and adenovirus; also, antigen presenting cells may be transfected with polynucleotide sequences disclosed herein by a variety of means, including gene-gun technology, lipid-mediated delivery, electroporation, osmotic shock, and particlate delivery mechanisms, resulting in efficient and acceptable expression levels as determined by one of ordinary skill in the art. For cultured T-cells to be effective in therapy, the cultured T-cells must be able to grow and distribute widely and to survive long term in vivo. Studies have demonstrated that cultured T-cells can be induced to grow in vivo and to survive long term in substantial numbers by repeated stimulation with antigen supplemented with IL-2 (see, for example, Cheever, M., et al, “Therapy With Cultured T Cells: Principles Revisited,” Immunological Reviews, 157:177, 1997).

The polypeptides disclosed herein may also be employed to generate and/or isolate chlamydial-reactive T-cells, which can then be administered to the patient. In one technique, antigen-specific T-cell lines may be generated by in vivo immunization with short peptides corresponding to immunogenic portions of the disclosed polypeptides. The resulting antigen specific CD8+ or CD4+ T-cell clones may be isolated from the patient, expanded using standard tissue culture techniques, and returned to the patient.

Alternatively, peptides corresponding to immunogenic portions of the polypeptides may be employed to generate Chlamydia reactive T cell subsets by selective in vitro stimulation and expansion of autologous T cells to provide antigen-specific T cells which may be subsequently transferred to the patient as described, for example, by Chang et al, ( Crit. Rev. Oncol. Hematol., 22(3), 213, 1996). Cells of the immune system, such as T cells, may be isolated from the peripheral blood of a patient, using a commercially available cell separation system, such as Isolex™ System, available from Nexell Therapeutics, Inc. Irvine, Calif. The separated cells are stimulated with one or more of the immunoreactive polypeptides contained within a delivery vehicle, such as a microsphere, to provide antigen-specific T cells. The population of antigen-specific T cells is then expanded using standard techniques and the cells are administered back to the patient.

In other embodiments, T-cell and/or antibody receptors specific for the polypeptides disclosed herein can be cloned, expanded, and transferred into other vectors or effector cells for use in adoptive immunotherapy. In particular, T cells may be transfected with the appropriate genes to express the variable domains from chlamydia specific monoclonal antibodies as the extracellular recognition elements and joined to the T cell receptor signaling chains, resulting in T cell activation, specific lysis, and cytokine release. This enables the T cell to redirect its specificity in an MHC-independent manner. See for example, Eshhar, Z., Cancer Immunol Immunother, 45(3-4):131-6, 1997 and Hwu, P., et al, Cancer Res, 55(15):3369-73, 1995. Another embodiment may include the transfection of chlamydia antigen specific alpha and beta T cell receptor chains into alternate T cells, as in Cole, D J, et al, Cancer Res, 55(4):748-52, 1995.

In a further embodiment, syngeneic or autologous dendritic cells may be pulsed with peptides corresponding to at least an immunogenic portion of a polypeptide disclosed herein. The resulting antigen-specific dendritic cells may either be transferred into a patient, or employed to stimulate T cells to provide antigen-specific T cells which may, in turn, be administered to a patient. The use of peptide-pulsed dendritic cells to generate antigen-specific T cells and the subsequent use of such antigen-specific T cells to eradicate disease in a murine model has been demonstrated by Cheever et al, Immunological Reviews, 157:177, 1997). Additionally, vectors expressing the disclosed polynucleotides may be introduced into stem cells taken from the patient and clonally propagated in vitro for autologous transplant back into the same patient.

Within certain aspects, polypeptides, polynucleotides, T cells and/or binding agents disclosed herein may be incorporated into pharmaceutical compositions or immunogenic compositions (i.e., vaccines). Alternatively, a pharmaceutical composition may comprise an antigen-presenting cell (e.g. a dendritic cell) transfected with a Chlamydial polynucleotide such that the antigen presenting cell expresses a Chlamydial polypeptide. Pharmaceutical compositions comprise one or more such compounds and a physiologically acceptable carrier. Vaccines may comprise one or more such compounds and an immunostimulant. An immunostimulant may be any substance that enhances or potentiates an immune response to an exogenous antigen. Examples of immunostimulants include adjuvants, biodegradable microspheres (e.g., polylactic galactide) and liposomes (into which the compound is incorporated; see e.g., Fullerton, U.S. Pat. No. 4,235,877). Vaccine preparation is generally described in, for example, M. F. Powell and M. J. Newman, eds., “Vaccine Design (the subunit and adjuvant approach),” Plenum Press (NY, 1995). Pharmaceutical compositions and vaccines within the scope of the present invention may also contain other compounds, which may be biologically active or inactive. For example, one or more immunogenic portions of other Chlamydial antigens may be present, either incorporated into a fusion polypeptide or as a separate compound, within the composition or vaccine.

A pharmaceutical composition or vaccine may contain DNA encoding one or more of the polypeptides as described above, such that the polypeptide is generated in situ. As noted above, the DNA may be present within any of a variety of delivery systems known to those of ordinary skill in the art, including nucleic acid expression systems, bacteria and viral expression systems. Numerous gene delivery techniques are well known in the art, such as those described by Rolland, Crit. Rev. Therap. Drug Carrier Systems 15:143-198, 1998, and references cited therein. Appropriate nucleic acid expression systems contain the necessary DNA sequences for expression in the patient (such as a suitable promoter and terminating signal). Bacterial delivery systems involve the administration of a bacterium (such as Bacillus-Calmette-Guerrin) that expresses an immunogenic portion of the polypeptide on its cell surface or secretes such an epitope.

In a preferred embodiment, the DNA may be introduced using a viral expression system (e.g., vaccinia or other pox virus, retrovirus, adenovirus, baculovirus, togavirus, bacteriophage, and the like), which often involves the use of a non-pathogenic (defective), replication competent virus.

For example, many viral expression vectors are derived from viruses of the retroviridae family. This family includes the murine leukemia viruses, the mouse mammary tumor viruses, the human foamy viruses, Rous sarcoma virus, and the immunodeficiency viruses, including human, simian, and feline. Considerations when designing retroviral expression vectors are discussed in Comstock et al. (1997).

Excellent murine leukemia virus (MLV)-based viral expression vectors have been developed by Kim et al. (1998). In creating the MLV vectors, Kim et al. found that the entire gag sequence, together with the immediate upstream region, could be deleted without significantly affecting viral packaging or gene expression. Further, it was found that nearly the entire U3 region could be replaced with the immediately-early promoter of human cytomegalovirus without deleterious effects. Additionally, MCR and internal ribosome entry sites (IRES) could be added without adverse effects. Based on their observations, Kim et al. have designed a series of MLV-based expression vectors comprising one or more of the features described above.

As more has been learned about human foamy virus (HFV), characteristics of HFV that are favorable for its use as an expression vector have been discovered. These characteristics include the expression of pol by splicing and start of translation at a defined initiation codon. Other aspects of HFV viral expression vectors are reviewed in Bodem et al. (1997).

Murakami et al. (1997) describe a Rous sarcoma virus (RSV)-based replication-competent avian retrovirus vectors, IR1 and IR2 to express a heterologous gene at a high level. In these vectors, the IRES derived from encephalomyocarditis virus (EMCV) was inserted between the env gene and the heterologous gene. The IR1 vector retains the splice-acceptor site that is present downstream of the env gene while the IR2 vector lacks it. Murakami et al. have shown high level expression of several different heterologous genes by these vectors.

Recently, a number of lentivirus-based retroviral expression vectors have been developed. Kafri et al. (1997) have shown sustained expression of genes delivered directly into liver and muscle by a human immunodeficiency virus (HIV)-based expression vector. One benefit of the system is the inherent ability of HIV to transduce non-dividing cells. Because the viruses of Kafri et al. are pseudotyped with vesicular stomatitis virus G glycoprotein (VSVG), they can transduce a broad range of tissues and cell types.

A large number of adenovirus-based expression vectors have been developed, primarily due to the advantages offered by these vectors in gene therapy applications. Adenovirus expression vectors and methods of using such vectors are the subject of a number of United States patents, including U.S. Pat. No. 5,698,202, U.S. Pat. No. 5,616,326, U.S. Pat. No. 5,585,362, and U.S. Pat. No. 5,518,913, all incorporated herein by reference.

Additional adenoviral constructs are described in Khatri et al. (1997) and Tomanin et al. (1997). Khatri et al. describe novel ovine adenovirus expression vectors and their ability to infect bovine nasal turbinate and rabbit kidney cells as well as a range of human cell type, including lung and foreskin fibroblasts as well as liver, prostate, breast, colon and retinal lines. Tomanin et al. describe adenoviral expression vectors containing the T7 RNA polymerase gene. When introduced into cells containing a heterologous gene operably linked to a T7 promoter, the vectors were able to drive gene expression from the T7 promoter. The authors suggest that this system may be useful for the cloning and expression of genes encoding cytotoxic proteins.

Poxviruses are widely used for the expression of heterologous genes in mammalian cells. Over the years, the vectors have been improved to allow high expression of the heterologous gene and simplify the integration of multiple heterologous genes into a single molecule. In an effort to diminish cytopathic effects and to increase safety, vaccinia virus mutant and other poxviruses that undergo abortive infection in mammalian cells are receiving special attention (Oertli et al., 1997). The use of poxviruses as expression vectors is reviewed in Carroll and Moss (1997).

Togaviral expression vectors, which includes alphaviral expression vectors have been used to study the structure and function of proteins and for protein production purposes. Attractive features of togaviral expression vectors are rapid and efficient gene expression, wide host range, and RNA genomes (Huang, 1996). Also, recombinant vaccines based on alphaviral expression vectors have been shown to induce a strong humoral and cellular immune response with good immunological memory and protective effects (Tubulekas et al., 1997). Alphaviral expression vectors and their use are discussed, for example, in Lundstrom (1997).

In one study, Li and Garoff (1996) used Semliki Forest virus (SFV) expression vectors to express retroviral genes and to produce retroviral particles in BHK-21 cells. The particles produced by this method had protease and reverse transcriptase activity and were infectious. Furthermore, no helper virus could be detected in the virus stocks. Therefore, this system has features that are attractive for its use in gene therapy protocols.

Baculoviral expression vectors have traditionally been used to express heterologous proteins in insect cells. Examples of proteins include mammalian chemokine receptors (Wang et al., 1997), reporter proteins such as green fluorescent protein (Wu et al., 1997), and FLAG fusion proteins (Wu et al., 1997; Koh et al., 1997). Recent advances in baculoviral expression vector technology, including their use in virion display vectors and expression in mammalian cells is reviewed by Possee (1997). Other reviews on baculoviral expression vectors include Jones and Morikawa (1996) and O'Reilly (1997).

Other suitable viral expression systems are disclosed, for example, in Fisher-Hoch et al., Proc. Natl. Acad. Sci. USA 86:317-321, 1989; Flexner et al., Ann. N.Y. Acad. Sci. 569:86-103, 1989; Flexner et al., Vaccine 8:17-21, 1990; U.S. Pat. Nos. 4,603,112, 4,769,330, and 5,017,487; WO 89/01973; U.S. Pat. No. 4,777,127; GB 2,200,651; EP 0,345,242; WO 91/02805; Berkner, Biotechniques 6:616-627, 1988; Rosenfeld et al., Science 252:431-434, 1991; Kolls et al., Proc. Natl. Acad. Sci. USA 91:215-219, 1994; Kass-Eisler et al., Proc. Natl. Acad. Sci. USA 90:11498-11502, 1993; Guzman et al., Circulation 88:2838-2848, 1993; and Guzman et al., Cir. Res. 73:1202-1207, 1993. Techniques for incorporating DNA into such expression systems are well known to those of ordinary skill in the art. In other systems, the DNA may be introduced as “naked” DNA, as described, for example, in Ulmer et al., Science 259:1745-1749, 1993 and reviewed by Cohen, Science 259:1691-1692, 1993. The uptake of naked DNA may be increased by coating the DNA onto biodegradable beads, which are efficiently transported into the cells.

It will be apparent that a vaccine may comprise a polynucleotide and/or a polypeptide component, as desired. It will also be apparent that a vaccine may contain pharmaceutically acceptable salts of the polynucleotides and/or polypeptides provided herein. Such salts may be prepared from pharmaceutically acceptable non-toxic bases, including organic bases (e.g., salts of primary, secondary and tertiary amines and basic amino acids) and inorganic bases (e.g., sodium, potassium, lithium, ammonium, calcium and magnesium salts). While any suitable carrier known to those of ordinary skill in the art may be employed in the pharmaceutical compositions of this invention, the type of carrier will vary depending on the mode of administration. Compositions of the present invention may be formulated for any appropriate manner of administration, including for example, topical, oral, nasal, intravenous, intracranial, intraperitoneal, subcutaneous or intramuscular administration. For parenteral administration, such as subcutaneous injection, the carrier preferably comprises water, saline, alcohol, a fat, a wax or a buffer. For oral administration, any of the above carriers or a solid carrier, such as mannitol, lactose, starch, magnesium stearate, sodium saccharine, talcum, cellulose, glucose, sucrose, and magnesium carbonate, may be employed. Biodegradable microspheres (e.g., polylactate polyglycolate) may also be employed as carriers for the pharmaceutical compositions of this invention. Suitable biodegradable microspheres are disclosed, for example, in U.S. Pat. Nos. 4,897,268 and 5,075,109.

Such compositions may also comprise buffers (e.g., neutral buffered saline or phosphate buffered saline), carbohydrates (e.g., glucose, mannose, sucrose or dextrans), mannitol, proteins, polypeptides or amino acids such as glycine, antioxidants, bacteriostats, chelating agents such as EDTA or glutathione, adjuvants (e.g., aluminum hydroxide), solutes that render the formulation isotonic, hypotonic or weakly hypertonic with the blood of a recipient, suspending agents, thickening agents and/or preservatives. Alternatively, compositions of the present invention may be formulated as a lyophilizate. Compounds may also be encapsulated within liposomes using well known technology.

Any of a variety of immunostimulants may be employed in the vaccines of this invention. For example, an adjuvant may be included. Most adjuvants contain a substance designed to protect the antigen from rapid catabolism, such as aluminum hydroxide or mineral oil, and a stimulator of immune responses, such as lipid A, Bortadella pertussis or Mycobacterium tuberculosis derived proteins. Suitable adjuvants are commercially available as, for example, Freund's Incomplete Adjuvant and Complete Adjuvant (Difco Laboratories, Detroit, Mich.); Merck Adjuvant 65 (Merck and Company, Inc., Rahway, N.J.); AS-2 (SmithKline Beecham, Philadelphia, Pa.); aluminum salts such as aluminum hydroxide gel (alum) or aluminum phosphate; salts of calcium, iron or zinc; an insoluble suspension of acylated tyrosine; acylated sugars; cationically or anionically derivatized polysaccharides; polyphosphazenes; biodegradable microspheres; monophosphoryl lipid A and quil A. Cytokines, such as GM-CSF or interleukin-2,-7, or -12, may also be used as adjuvants.

Within the vaccines provided herein, under select circumstances, the adjuvant composition may be designed to induce an immune response predominantly of the Th1 type or Th2 type. High levels of Th1-type cytokines (e.g, IFN-γ, TNFα, IL-2 and IL-12) tend to favor the induction of cell mediated immune responses to an administered antigen. In contrast, high levels of Th2-type cytokines (e.g., IL-4, IL-5, IL-6 and IL-10) tend to favor the induction of humoral immune responses. Following application of a vaccine as provided herein, a patient will support an immune response that includes Th1- and Th2-type responses. Within a preferred embodiment, in which a response is predominantly Th1-type, the level of Th1-type cytokines will increase to a greater extent than the level of Th2-type cytokines. The levels of these cytokines may be readily assessed using standard assays. For a review of the families of cytokines, see Mosmann and Coffinan, Ann. Rev. Immunol. 7:145-173, 1989.

Preferred adjuvants for use in eliciting a predominantly Th1-type response include, for example, a combination of monophosphoryl lipid A, preferably 3-de-O-acylated monophosphoryl lipid A (3D-MPL), together with an aluminum salt. MPL adjuvants are available from Corixa Corporation (Seattle, Wash.; see U.S. Pat. Nos. 4,436,727; 4,877,611; 4,866,034 and 4,912,094). CpG-containing oligonucleotides (in which the CpG dinucleotide is unmethylated) also induce a predominantly Th1 response. Such oligonucleotides are well known and are described, for example, in WO 96/02555 and WO 99/33488. Immunostimulatory DNA sequences are also described, for example, by Sato et al., Science 273:352, 1996. Another preferred adjuvant is a saponin, preferably QS21 (Aquila Biopharmaceuticals Inc., Framingham, Mass.), which may be used alone or in combination with other adjuvants. For example, an enhanced system involves the combination of a monophosphoryl lipid A and saponin derivative, such as the combination of QS21 and 3D-MPL as described in WO 94/00153, or a less reactogenic composition where the QS21 is quenched with cholesterol, as described in WO 96/33739. Other preferred formulations comprise an oil-in-water emulsion and tocopherol. A particularly potent adjuvant formulation involving QS21, 3D-MPL and tocopherol in an oil-in-water emulsion is described in WO 95/17210.

Other preferred adjuvants include Montanide ISA 720 (Seppic, France), SAF (Chiron, Calif., United States), ISCOMS (CSL), MF-59 (Chiron), the SBAS series of adjuvants (e.g., SBAS-2 or SBAS-4, available from SmithKline Beecham, Rixensart, Belgium), Detox (Corixa Corporation; Seattle, Wash.), RC-529 (Corixa Corporation; Seattle, Wash.) and other aminoalkyl glucosaminide 4-phosphates (AGPs), such as those described in pending U.S. patent application Ser. Nos. 08/853,826 and 09/074,720, the disclosures of which are incorporated herein by reference in their entireties.

Any vaccine provided herein may be prepared using well known methods that result in a combination of antigen, immunostimulant and a suitable carrier or excipient. The compositions described herein may be administered as part of a sustained release formulation (i.e., a formulation such as a capsule, sponge or gel (composed of polysaccharides, for example) that effects a slow release of compound following administration). Such formulations may generally be prepared using well known technology (see, e.g., Coombes et al., Vaccine 14:1429-1438, 1996) and administered by, for example, oral, rectal or subcutaneous implantation, or by implantation at the desired target site. Sustained-release formulations may contain a polypeptide, polynucleotide or antibody dispersed in a carrier matrix and/or contained within a reservoir surrounded by a rate controlling membrane.

Carriers for use within such formulations are biocompatible, and may also be biodegradable; preferably the formulation provides a relatively constant level of active component release. Such carriers include microparticles of poly(lactide-co-glycolide), as well as polyacrylate, latex, starch, cellulose and dextran. Other delayed-release carriers include supramolecular biovectors, which comprise a non-liquid hydrophilic core (e.g., a cross-linked polysaccharide or oligosaccharide) and, optionally, an external layer comprising an amphiphilic compound, such as a phospholipid (see e.g., U.S. Pat. No. 5,151,254 and PCT applications WO 94/20078, WO/94/23701 and WO 96/06638). The amount of active compound contained within a sustained release formulation depends upon the site of implantation, the rate and expected duration of release and the nature of the condition to be treated or prevented.

Any of a variety of delivery vehicles may be employed within pharmaceutical compositions and vaccines to facilitate production of an antigen-specific immune response that targets Chlamydia-infected cells. Delivery vehicles include antigen presenting cells (APCs), such as dendritic cells, macrophages, B cells, monocytes and other cells that may be engineered to be efficient APCs. Such cells may, but need not, be genetically modified to increase the capacity for presenting the antigen, to improve activation and/or maintenance of the T cell response, to have anti-Chlamydia effects per se and/or to be immunologically compatible with the receiver (i.e., matched HLA haplotype). APCs may generally be isolated from any of a variety of biological fluids and organs, and may be autologous, allogeneic, syngeneic or xenogeneic cells.

Certain preferred embodiments of the present invention use dendritic cells or progenitors thereof as antigen-presenting cells. Dendritic cells are highly potent APCs (Banchereau and Steinman, Nature 392:245-251, 1998) and have been shown to be effective as a physiological adjuvant for eliciting prophylactic or therapeutic immunity (see Timmerman and Levy, Ann. Rev. Med. 50:507-529, 1999). In general, dendritic cells may be identified based on their typical shape (stellate in situ, with marked cytoplasmic processes (dendrites) visible in vitro), their ability to take up, process and present antigens with high efficiency, and their ability to activate naive T cell responses. Dendritic cells may, of course, be engineered to express specific cell-surface receptors or ligands that are not commonly found on dendritic cells in vivo or ex vivo, and such modified dendritic cells are contemplated by the present invention. As an alternative to dendritic cells, secreted vesicles antigen-loaded dendritic cells (called exosomes) may be used within a vaccine (see Zitvogel et al., Nature Med. 4:594-600, 1998).

Dendritic cells and progenitors may be obtained from peripheral blood, bone marrow, lymph nodes, spleen, skin, umbilical cord blood or any other suitable tissue or fluid. For example, dendritic cells may be differentiated ex vivo by adding a combination of cytokines such as GM-CSF, IL-4, IL-13 and/or TNFα to cultures of monocytes harvested from peripheral blood. Alternatively, CD34 positive cells harvested from peripheral blood, umbilical cord blood or bone marrow may be differentiated into dendritic cells by adding to the culture medium combinations of GM-CSF, IL-3, TNFα, CD40 ligand, LPS, flt3 ligand and/or other compound(s) that induce differentiation, maturation and proliferation of dendritic cells.

Dendritic cells are conveniently categorized as “immature” and “mature” cells, which allows a simple way to discriminate between two well characterized phenotypes. However, this nomenclature should not be construed to exclude all possible intermediate stages of differentiation. Immature dendritic cells are characterized as APC with a high capacity for antigen uptake and processing, which correlates with the high expression of Fcγ receptor and mannose receptor. The mature phenotype is typically characterized by a lower expression of these markers, but a high expression of cell surface molecules responsible for T cell activation such as class I and class II MHC, adhesion molecules (e.g., CD54 and CD11) and costimulatory molecules (e.g, CD40, CD80, CD86 and4-1BB).

APCs may generally be transfected with a polynucleotide encoding a Chlamydial protein (or portion or other variant thereof) such that the Chlamydial polypeptide, or an immunogenic portion thereof, is expressed on the cell surface. Such transfection may take place ex vivo, and a composition or vaccine comprising such transfected cells may then be used for therapeutic purposes, as described herein. Alternatively, a gene delivery vehicle that targets a dendritic or other antigen presenting cell may be administered to a patient, resulting in transfection that occurs in vivo. In vivo and ex vivo transfection of dendritic cells, for example, may generally be performed using any methods known in the art, such as those described in WO 97/24447, or the gene gun approach described by Mahvi et al., Immunology and cell Biology 75:456-460, 1997. Antigen loading of dendritic cells may be achieved by incubating dendritic cells or progenitor cells with the Chlamydial polypeptide, DNA (naked or within a plasmid vector) or RNA; or with antigen-expressing recombinant bacterium or viruses (e.g., vaccinia, fowlpox, adenovirus or lentivirus vectors). Prior to loading, the polypeptide may be covalently conjugated to an immunological partner that provides T cell help (e.g., a carrier molecule). Alternatively, a dendritic cell may be pulsed with a non-conjugated immunological partner, separately or in the presence of the polypeptide.

Routes and frequency of administration of pharmaceutical compositions and vaccines, as well as dosage, will vary from individual to individual. In general, the pharmaceutical compositions and vaccines may be administered by injection (e.g., intracutaneous, intramuscular, intravenous or subcutaneous), intranasally (e.g., by aspiration) or orally. Between 1 and 3 doses may be administered for a 1-36 week period. Preferably, 3 doses are administered, at intervals of 3-4 months, and booster vaccinations may be given periodically thereafter. Alternate protocols may be appropriate for individual patients. A suitable dose is an amount of polypeptide or DNA that, when administered as described above, is capable of raising an immune response in an immunized patient sufficient to protect the patient from Chlamydial infection for at least 1-2 years. In general, the amount of polypeptide present in a dose (or produced in situ by the DNA in a dose) ranges from about 1 pg to about 100 mg per kg of host, typically from about 10 pg to about 1 mg, and preferably from about 100 pg to about 1 μg. Suitable dose sizes will vary with the size of the patient, but will typically range from about 0.1 mL to about 5 mL.

While any suitable carrier known to those of ordinary skill in the art may be employed in the pharmaceutical compositions of this invention, the type of carrier will vary depending on the mode of administration. For parenteral administration, such as subcutaneous injection, the carrier preferably comprises water, saline, alcohol, a fat, a wax or a buffer. For oral administration, any of the above carriers or a solid carrier, such as mannitol, lactose, starch, magnesium stearate, sodium saccharine, talcum, cellulose, glucose, sucrose, and magnesium carbonate, may be employed. Biodegradable microspheres (e.g., polylactic galactide) may also be employed as carriers for the pharmaceutical compositions of this invention. Suitable biodegradable microspheres are disclosed, for example, in U.S. Pat. Nos. 4,897,268 and 5,075,109.

In general, an appropriate dosage and treatment regimen provides the active compound(s) in an amount sufficient to provide therapeutic and/or prophylactic benefit. Such a response can be monitored by establishing an improved clinical outcome in treated patients as compared to non-treated patients. Increases in preexisting immune responses to a Chlamydial protein generally correlate with an improved clinical outcome. Such immune responses may generally be evaluated using standard proliferation, cytotoxicity or cytokine assays, which may be performed using samples obtained from a patient before and after treatment.

Detection and Diagnosis

In another aspect, the present invention provides methods for using the polypeptides described above to diagnose Chlamydial infection. In this aspect, methods are provided for detecting Chlamydial infection in a biological sample, using one or more of the above polypeptides, either alone or in combination. For clarity, the term “polypeptide” will be used when describing specific embodiments of the inventive diagnostic methods. However, it will be clear to one of skill in the art that the fusion proteins of the present invention may also be employed in such methods.

As used herein, a “biological sample” is any antibody-containing sample obtained from a patient. Preferably, the sample is whole blood, sputum, serum, plasma, saliva, cerebrospinal fluid or urine. More preferably, the sample is a blood, serum or plasma sample obtained from a patient. The polypeptides are used in an assay, as described below, to determine the presence or absence of antibodies to the polypeptide(s) in the sample, relative to a predetermined cut-off value. The presence of such antibodies indicates previous sensitization to Chlamydia antigens which may be indicative of Chlamydia-infection.

In embodiments in which more than one polypeptide is employed, the polypeptides used are preferably complementary (i.e., one component polypeptide will tend to detect infection in samples where the infection would not be detected by another component polypeptide). Complementary polypeptides may generally be identified by using each polypeptide individually to evaluate serum samples obtained from a series of patients known to be infected with Chlamydia. After determining which samples test positive (as described below) with each polypeptide, combinations of two or more polypeptides may be formulated that are capable of detecting infection in most, or all, of the samples tested.

A variety of assay formats are known to those of ordinary skill in the art for using one or more polypeptides to detect antibodies in a sample. See, e.g., Harlow and Lane, Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, 1988, which is incorporated herein by reference. In a preferred embodiment, the assay involves the use of polypeptide immobilized on a solid support to bind to and remove the antibody from the sample. The bound antibody may then be detected using a detection reagent that contains a reporter group. Suitable detection reagents include antibodies that bind to the antibody/polypeptide complex and free polypeptide labeled with a reporter group (e.g., in a semi-competitive assay). Alternatively, a competitive assay may be utilized, in which an antibody that binds to the polypeptide is labeled with a reporter group and allowed to bind to the immobilized antigen after incubation of the antigen with the sample. The extent to which components of the sample inhibit the binding of the labeled antibody to the polypeptide is indicative of the reactivity of the sample with the immobilized polypeptide.

The solid support may be any solid material known to those of ordinary skill in the art to which the antigen may be attached. For example, the solid support may be a test well in a microtiter plate, or a nitrocellulose or other suitable membrane. Alternatively, the support may be a bead or disc, such as glass, fiberglass, latex or a plastic material such as polystyrene or polyvinylchloride. The support may also be a magnetic particle or a fiber optic sensor, such as those disclosed, for example, in U.S. Pat. No. 5,359,681.

The polypeptides may be bound to the solid support using a variety of techniques known to those of ordinary skill in the art. In the context of the present invention, the term “bound” refers to both noncovalent association, such as adsorption, and covalent attachment (which may be a direct linkage between the antigen and functional groups on the support or may be a linkage by way of a cross-linking agent). Binding by adsorption to a well in a microtiter plate or to a membrane is preferred. In such cases, adsorption may be achieved by contacting the polypeptide, in a suitable buffer, with the solid support for a suitable amount of time. The contact time varies with temperature, but is typically between about 1 hour and 1 day. In general, contacting a well of a plastic microtiter plate (such as polystyrene or polyvinylchloride) with an amount of polypeptide ranging from about 10 ng to about 1 μg, and preferably about 100 ng, is sufficient to bind an adequate amount of antigen.

Covalent attachment of polypeptide to a solid support may generally be achieved by first reacting the support with a bifunctional reagent that will react with both the support and a functional group, such as a hydroxyl or amino group, on the polypeptide. For example, the polypeptide may be bound to supports having an appropriate polymer coating using benzoquinone or by condensation of an aldehyde group on the support with an amine and an active hydrogen on the polypeptide (see, e.g., Pierce Immunotechnology Catalog and Handbook, 1991, at A12-A13).

In certain embodiments, the assay is an enzyme linked immunosorbent assay (ELISA). This assay may be performed by first contacting a polypeptide antigen that has been immobilized on a solid support, commonly the well of a microtiter plate, with the sample, such that antibodies to the polypeptide within the sample are allowed to bind to the immobilized polypeptide. Unbound sample is then removed from the immobilized polypeptide and a detection reagent capable of binding to the immobilized antibody-polypeptide complex is added. The amount of detection reagent that remains bound to the solid support is then determined using a method appropriate for the specific detection reagent.

More specifically, once the polypeptide is immobilized on the support as described above, the remaining protein binding sites on the support are typically blocked. Any suitable blocking agent known to those of ordinary skill in the art, such as bovine serum albumin (BSA) or Tween 20™ (Sigma Chemical Co., St. Louis, Mo.) may be employed. The immobilized polypeptide is then incubated with the sample, and antibody is allowed to bind to the antigen. The sample may be diluted with a suitable dilutent, such as phosphate-buffered saline (PBS) prior to incubation. In general, an appropriate contact time (i.e., incubation time) is that period of time that is sufficient to detect the presence of antibody within an HGE-infected sample. Preferably, the contact time is sufficient to achieve a level of binding that is at least 95% of that achieved at equilibrium between bound and unbound antibody. Those of ordinary skill in the art will recognize that the time necessary to achieve equilibrium may be readily determined by assaying the level of binding that occurs over a period of time. At room temperature, an incubation time of about 30 minutes is generally sufficient.

Unbound sample may then be removed by washing the solid support with an appropriate buffer, such as PBS containing 0.1% Tween 20™. Detection reagent may then be added to the solid support. An appropriate detection reagent is any compound that binds to the immobilized antibody-polypeptide complex and that can be detected by any of a variety of means known to those in the art. Preferably, the detection reagent contains a binding agent (such as, for example, Protein A, Protein G, immunoglobulin, lectin or free antigen) conjugated to a reporter group. Preferred reporter groups include enzymes (such as horseradish peroxidase), substrates, cofactors, inhibitors, dyes, radionuclides, luminescent groups, fluorescent groups and biotin. The conjugation of binding agent to reporter group may be achieved using standard methods known to those of ordinary skill in the art. Common binding agents may also be purchased conjugated to a variety of reporter groups from many commercial sources (e.g., Zymed Laboratories, San Francisco, Calif., and Pierce, Rockford, Ill.).

The detection reagent is then incubated with the immobilized antibody-polypeptide complex for an amount of time sufficient to detect the bound antibody. An appropriate amount of time may generally be determined from the manufacturer's instructions or by assaying the level of binding that occurs over a period of time. Unbound detection reagent is then removed and bound detection reagent is detected using the reporter group. The method employed for detecting the reporter group depends upon the nature of the reporter group. For radioactive groups, scintillation counting or autoradiographic methods are generally appropriate. Spectroscopic methods may be used to detect dyes, luminescent groups and fluorescent groups. Biotin may be detected using avidin, coupled to a different reporter group (commonly a radioactive or fluorescent group or an enzyme). Enzyme reporter groups may generally be detected by the addition of substrate (generally for a specific period of time), followed by spectroscopic or other analysis of the reaction products.

To determine the presence or absence of anti-Chlamydia antibodies in the sample, the signal detected from the reporter group that remains bound to the solid support is generally compared to a signal that corresponds to a predetermined cut-off value. In one preferred embodiment, the cut-off value is the average mean signal obtained when the immobilized antigen is incubated with samples from an uninfected patient. In general, a sample generating a signal that is three standard deviations above the predetermined cut-off value is considered positive for Chlamydia-infection. In an alternate preferred embodiment, the cut-off value is determined using a Receiver Operator Curve, according to the method of Sackett et al., Clinical Epidemiology: A Basic Science for Clinical Medicine, Little Brown and Co., 1985, pp. 106-107. Briefly, in this embodiment, the cut-off value may be determined from a plot of pairs of true positive rates (i.e., sensitivity) and false positive rates (100%-specificity) that correspond to each possible cut-off value for the diagnostic test result. The cut-off value on the plot that is the closest to the upper left-hand comer (i.e., the value that encloses the largest area) is the most accurate cut-off value, and a sample generating a signal that is higher than the cut-off value determined by this method may be considered positive. Alternatively, the cut-off value may be shifted to the left along the plot, to minimize the false positive rate, or to the right, to minimize the false negative rate. In general, a sample generating a signal that is higher than the cut-off value determined by this method is considered positive for Chlamydial infection.

In a related embodiment, the assay is performed in a rapid flow-through or strip test format, wherein the antigen is immobilized on a membrane, such as nitrocellulose. In the flow-through test, antibodies within the sample bind to the immobilized polypeptide as the sample passes through the membrane. A detection reagent (e.g., protein A-colloidal gold) then binds to the antibody-polypeptide complex as the solution containing the detection reagent flows through the membrane. The detection of bound detection reagent may then be performed as described above. In the strip test format, one end of the membrane to which polypeptide is bound is immersed in a solution containing the sample. The sample migrates along the membrane through a region containing detection reagent and to the area of immobilized polypeptide. Concentration of detection reagent at the polypeptide indicates the presence of anti-Chlamydia antibodies in the sample. Typically, the concentration of detection reagent at that site generates a pattern, such as a line, that can be read visually. The absence of such a pattern indicates a negative result. In general, the amount of polypeptide immobilized on the membrane is selected to generate a visually discernible pattern when the biological sample contains a level of antibodies that would be sufficient to generate a positive signal in an ELISA, as discussed above. Preferably, the amount of polypeptide immobilized on the membrane ranges from about 25 ng to about 1 μg, and more preferably from about 50 ng to about 500 ng. Such tests can typically be performed with a very small amount (e.g., one drop) of patient serum or blood.

Of course, numerous other assay protocols exist that are suitable for use with the polypeptides of the present invention. The above descriptions are intended to be exemplary only. One example of an alternative assay protocol which may be usefully employed in such methods is a Western blot, wherein the proteins present in a biological sample are separated on a gel, prior to exposure to a binding agent. Such techniques are well known to those of skill in the art.

Binding Agents and Their Uses

The present invention further provides agents, such as antibodies and antigen-binding fragments thereof, that specifically bind to a Chlamydial protein. As used herein, an antibody, or antigen-binding fragment thereof, is said to “specifically bind” to a Chlamydial protein if it reacts at a detectable level (within, for example, an ELISA) with a Chlamydial protein, and does not react detectably with unrelated proteins under similar conditions. As used herein, “binding” refers to a noncovalent association between two separate molecules such that a complex is formed. The ability to bind may be evaluated by, for example, determining a binding constant for the formation of the complex. The binding constant is the value obtained when the concentration of the complex is divided by the product of the component concentrations. In general, two compounds are said to “bind,” in the context of the present invention, when the binding constant for complex formation exceeds about 10 ³L/mol. The binding constant may be determined using methods well known in the art.

Binding agents may be further capable of differentiating between patients with and without a Chlamydial infection using the representative assays provided herein. In other words, antibodies or other binding agents that bind to a Chlamydial protein will generate a signal indicating the presence of a Chlamydial infection in at least about 20% of patients with the disease, and will generate a negative signal indicating the absence of the disease in at least about 90% of individuals without infection. To determine whether a binding agent satisfies this requirement, biological samples (e.g., blood, sera, sputum urine and/or tissue biopsies) from patients with and without Chlamydial infection (as determined using standard clinical tests) may be assayed as described herein for the presence of polypeptides that bind to the binding agent. It will be apparent that a statistically significant number of samples with and without the disease should be assayed. Each binding agent should satisfy the above criteria; however, those of ordinary skill in the art will recognize that binding agents may be used in combination to improve sensitivity.

Any agent that satisfies the above requirements may be a binding agent. For example, a binding agent may be a ribosome, with or without a peptide component, an RNA molecule or a polypeptide. In a preferred embodiment, a binding agent is an antibody or an antigen-binding fragment thereof. Antibodies may be prepared by any of a variety of techniques known to those of ordinary skill in the art. See, e.g., Harlow and Lane, Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, 1988. In general, antibodies can be produced by cell culture techniques, including the generation of monoclonal antibodies as described herein, or via transfection of antibody genes into suitable bacterial or mammalian cell hosts, in order to allow for the production of recombinant antibodies. In one technique, an immunogen comprising the polypeptide is initially injected into any of a wide variety of mammals (e.g., mice, rats, rabbits, sheep or goats). In this step, the polypeptides of this invention may serve as the immunogen without modification. Alternatively, particularly for relatively short polypeptides, a superior immune response may be elicited if the polypeptide is joined to a carrier protein, such as bovine serum albumin or keyhole limpet hemocyanin. The immunogen is injected into the animal host, preferably according to a predetermined schedule incorporating one or more booster immunizations, and the animals are bled periodically. Polyclonal antibodies specific for the polypeptide may then be purified from such antisera by, for example, affinity chromatography using the polypeptide coupled to a suitable solid support.

Monoclonal antibodies specific for an antigenic polypeptide of interest may be prepared, for example, using the technique of Kohler and Milstein, Eur. J Immunol. 6:511-519, 1976, and improvements thereto. Briefly, these methods involve the preparation of immortal cell lines capable of producing antibodies having the desired specificity (i.e., reactivity with the polypeptide of interest). Such cell lines may be produced, for example, from spleen cells obtained from an animal immunized as described above. The spleen cells are then immortalized by, for example, fusion with a myeloma cell fusion partner, preferably one that is syngeneic with the immunized animal. A variety of fusion techniques may be employed. For example, the spleen cells and myeloma cells may be combined with a nonionic detergent for a few minutes and then plated at low density on a selective medium that supports the growth of hybrid cells, but not myeloma cells. A preferred selection technique uses HAT (hypoxanthine, aminopterin, thymidine) selection. After a sufficient time, usually about 1 to 2 weeks, colonies of hybrids are observed. Single colonies are selected and their culture supernatants tested for binding activity against the polypeptide. Hybridomas having high reactivity and specificity are preferred.

Monoclonal antibodies may be isolated from the supernatants of growing hybridoma colonies. In addition, various techniques may be employed to enhance the yield, such as injection of the hybridoma cell line into the peritoneal cavity of a suitable vertebrate host, such as a mouse. Monoclonal antibodies may then be harvested from the ascites fluid or the blood. Contaminants may be removed from the antibodies by conventional techniques, such as chromatography, gel filtration, precipitation, and extraction. The polypeptides of this invention may be used in the purification process in, for example, an affinity chromatography step.

Within certain embodiments, the use of antigen-binding fragments of antibodies may be preferred. Such fragments include Fab fragments, which may be prepared using standard techniques. Briefly, immunoglobulins may be purified from rabbit serum by affinity chromatography on Protein A bead columns (Harlow and Lane, Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, 1988) and digested by papain to yield Fab and Fc fragments. The Fab and Fc fragments may be separated by affinity chromatography on protein A bead columns.

Monoclonal antibodies of the present invention may be coupled to one or more therapeutic agents. Suitable agents in this regard include radionuclides, differentiation inducers, drugs, toxins, and derivatives thereof. Preferred radionuclides include ⁹⁰Y, ¹²³I, ¹²⁵I, ¹³¹I, ¹⁸⁶Re, ¹⁸⁸Re, ²¹¹At, and ²¹²Bi. Preferred drugs include methotrexate, and pyrimidine and purine analogs. Preferred differentiation inducers include phorbol esters and butyric acid. Preferred toxins include ricin, abrin, diptheria toxin, cholera toxin, gelonin, Pseudomonas exotoxin, Shigella toxin, and pokeweed antiviral protein.

A therapeutic agent may be coupled (e.g. covalently bonded) to a suitable monoclonal antibody either directly or indirectly (e.g., via a linker group). A direct reaction between an agent and an antibody is possible when each possesses a substituent capable of reacting with the other. For example, a nucleophilic group, such as an amino or sulfhydryl group, on one may be capable of reacting with a carbonyl-containing group, such as an anhydride or an acid halide, or with an alkyl group containing a good leaving group (e.g., a halide) on the other.

Alternatively, it may be desirable to couple a therapeutic agent and an antibody via a linker group. A linker group can function as a spacer to distance an antibody from an agent in order to avoid interference with binding capabilities. A linker group can also serve to increase the chemical reactivity of a substituent on an agent or an antibody, and thus increase the coupling efficiency. An increase in chemical reactivity may also facilitate the use of agents, or functional groups on agents, which otherwise would not be possible.

It will be evident to those skilled in the art that a variety of bifunctional or polyfunctional reagents, both homo- and hetero-functional (such as those described in the catalog of the Pierce Chemical Co., Rockford, Ill.), may be employed as the linker group. Coupling may be effected, for example, through amino groups, carboxyl groups, sulfhydryl groups or oxidized carbohydrate residues. There are numerous references describing such methodology, e.g., U.S. Pat. No. 4,671,958, to Rodwell et al.

Where a therapeutic agent is more potent when free from the antibody portion of the immunoconjugates of the present invention, it may be desirable to use a linker group which is cleavable during or upon internalization into a cell. A number of different cleavable linker groups have been described. The mechanisms for the intracellular release of an agent from these linker groups include cleavage by reduction of a disulfide bond (e.g., U.S. Pat. No. 4,489,710, to Spitler), by irradiation of a photolabile bond (e.g., U.S. Pat. No. 4,625,014, to Senter et al.), by hydrolysis of derivatized amino acid side chains (e.g., U.S. Pat. No. 4,638,045, to Kohn et al.), by serum complement-mediated hydrolysis (e.g, U.S. Pat. No. 4,671,958, to Rodwell et al.), and acid-catalyzed hydrolysis (e.g., U.S. Pat. No. 4,569,789, to Blattler et al.).

It may be desirable to couple more than one agent to an antibody. In one embodiment, multiple molecules of an agent are coupled to one antibody molecule. In another embodiment, more than one type of agent may be coupled to one antibody. Regardless of the particular embodiment, immunoconjugates with more than one agent may be prepared in a variety of ways. For example, more than one agent may be coupled directly to an antibody molecule, or linkers which provide multiple sites for attachment can be used. Alternatively, a carrier can be used.

A carrier may bear the agents in a variety of ways, including covalent bonding either directly or via a linker group. Suitable carriers include proteins such as albumins (e.g., U.S. Pat. No. 4,507,234, to Kato et al.), peptides and polysaccharides such as aminodextran (e.g., U.S. Pat. No. 4,699,784, to Shih et al.). A carrier may also bear an agent by noncovalent bonding or by encapsulation, such as within a liposome vesicle (e.g., U.S. Pat. Nos. 4,429,008 and 4,873,088). Carriers specific for radionuclide agents include radiohalogenated small molecules and chelating compounds. For example, U.S. Pat. No. 4,735,792 discloses representative radiohalogenated small molecules and their synthesis. A radionuclide chelate may be formed from chelating compounds that include those containing nitrogen and sulfur atoms as the donor atoms for binding the metal, or metal oxide, radionuclide. For example, U.S. Pat. No. 4,673,562, to Davison et al. discloses representative chelating compounds and their synthesis.

A variety of routes of administration for the antibodies and immunoconjugates may be used. Typically, administration will be intravenous, intramuscular, subcutaneous or in site-specific regions by appropriate methods. It will be evident that the precise dose of the antibody/immunoconjugate will vary depending upon the antibody used, the antigen density, and the rate of clearance of the antibody.

Antibodies may be used in diagnostic tests to detect the presence of Chlamydia antigens using assays similar to those detailed above and other techniques well known to those of skill in the art, thereby providing a method for detecting Chlamydial infection in a patient.

Diagnostic reagents of the present invention may also comprise DNA sequences encoding one or more of the above polypeptides, or one or more portions thereof. For example, at least two oligonucleotide primers may be employed in a polymerase chain reaction (PCR) based assay to amplify Chlamydia-specific cDNA derived from a biological sample, wherein at least one of the oligonucleotide primers is specific for a DNA molecule encoding a polypeptide of the present invention. The presence of the amplified cDNA is then detected using techniques well known in the art, such as gel electrophoresis. Similarly, oligonucleotide probes specific for a DNA molecule encoding a polypeptide of the present invention may be used in a hybridization assay to detect the presence of an inventive polypeptide in a biological sample.

The following Examples are offered by way of illustration and not by way of limitation.

EXAMPLE 1

CD4 T Cell Expression Cloning for the Identification of T Cell Stimulating Antigens from [0412] Chlamydia Trachomatis Serovar E
In this example, a CD4+ T cell expression cloning strategy was used to identify [0413] Chlamydia trachomatis antigens recognized by patients enrolled in Corixa Corporation's blood donor program. A genomic library of Chlamydia trachomatis serovar E was constructed and screened with Chlamydia specific T cell lines generated by stimulating PBMCs from these donors. Donor CT1 is a 27 yr. old male whose clinical manifestation was non-gonococcal urethritis and his urine was tested positive for Chlamydia by ligase chain reaction. Donor CT3 is a 43 yr. old male who is asymptomatic and infected with serovar J. Donor CT10 is a 24 yr. old female who is asymptomatic and was exposed to Chlamydia through her partner but did not develop the disease. Donor CT11 is a 24 yr. old female with multiple infections (serovar J, F and E).
Chlamydia specific T-cell lines were generated from donors with chlamydial genital tract infection or donors exposed to chlamydia who did not develop the disease. T cell lines from donor CT-1, CT-3 and CT-10 were generated by stimulating PBMC's with reticulate bodies of [0414] C. trachomatis serovar E. T-cell lines from donor CT-11 were generated by stimulating PBMC's with either reticulate bodies or elementary bodies of C. trachomatis serovar E. A randomly sheared genomic library of C. trachomatis serovar E was constructed in lambda Zap II vector and an amplified library plated out in 96 well microtiter plates at a density of 25 clones/well. Bacteria were induced to express the recombinant protein in the presence of 2 mM IPTG for 2 hr, then pelleted and resuspended in 200 ul RPMI/10% FBS. 10 ul of the induced bacterial suspension was transferred to 96 well plates containing autologous monocyte-derived dendritic cells. After a 2 hour incubation, dendritic cells were washed to remove E. coli and the T cells were added. Positive E. coli pools were identified by determining IFN gamma production and proliferation of T cells in the pools. The number of pools identified by each T-cell line is as follows: CT1 line: 30/480 pools; CT3 line: 91/960 pools; CT10 line: 40/480 pools; CT11 line : 51/480 pools. The clones identified using this approach are set forth in SEQ ID NO: 1-14.
In another example using substantially the same approach described above, we identified 12 additional T-cell reactive clones from [0415] Chlamydia trachomatis serovar E expression screening. Clone E5-E9-3 (CT1 positive) contains a 636 bp insert that encodes partially the ORF for dnaK like gene. Part of this sequence was also identified in clone E1-A5-53. Clone E4-H3-56 (CT1 positive, 463 bp insert) contains a partial ORF for the TSA gene (CT603) on the complementary strand. The insert for clone E2-G12-52 (1265 bp) was identified with the CT11 line. It contains a partial ORF for clpB, a protease ATPase. Another clone identified with the CT11 line, E1-F9-79 (167 bp), contains a partial ORF for the gene CT133 on the complementary strand. CT133 is a predicted rRNA methylase. Clone E4-D2-79 (CT3 positive) contains a 1181 bp insert that is a partial ORF for nrdA gene. The ORF for this gene was also identified in clone E2-B10-52 (CT10 positive). Clone E6-C8-95 contains a 731 bp insert that was identified using the donor lines CT3, CT1, and CT12. This insert has a carboxy terminal half for the gene for the 60 kDa ORF. Clone E7-H11-61 (CT3 positive-1135 bp) has partial inserts for fliA (CT061), tyrS (CT062), TSA (CT603) and a hypothetical protein (CT602). The insert for clone E5-A11-8 (CT10 positive-1736 bp) contains the complete ORF for groES (CT111) and a majority of the ORF for groEL (CT110). Clone E3-F2-37 (CT10, CT3, CT11, and CT12 positive-1377 bp insert) contains a partial ORF for gene tRNA-Trp (CT322) and a complete ORF for the gene secE (CT321). E4-G9-75 is another CT10 clone that contains a partial ORF (723 bp insert) for the amino terminal region of the pmpH gene (CT872). Clone E2-D5-89 (516 bp) is also a CT10 positive clone that contains a partial ORF for pmpD gene (12). The insert for clone E5-E2-10 (CT10 positive) is 427 bp and contains a partial ORF for the major outer membrane protein omp 1.

EXAMPLE 2

Additional CD4 T Cell Expression Cloning for the Identification of T Cell Stimulating Antigens from [0416] Chlamydia Trachomatis Serovar E
Twenty sequences were isolated from single clones using a Chlamydia trachomatis serovar E (Ct E) library expression screening method. Descriptions of how the clones and lines were generated are provided in Example 1. [0417]
Clone E5-A8-85 (identified using the CT1 patient line) was found to contain a 1433 bp insert. This insert contains a large region of the C-terminal half of the CT875, a [0418] Chlamydia trachomatis hypothetical specific gene that is disclosed in SEQ ID NO: 34. Also present in the clone is a partial open reading frame (ORF) of a hypothetical protein CT001 which is on the complementary strand.
The clone E9-G2-93 (identified using the C10 patient line) was shown to contain a 554 bp insert, the sequence of which is disclosed in SEQ ID NO: 33. This sequence encodes a partial ORF for CT178, a hypothetical CT protein. [0419]
Clone E7-B1-16 (identified using the patient lines CT10, CT3, CT5, CT11, CT13, and CHH037) has a 2577 bp insert, the sequence of which is disclosed in SEQ ID NO: 32. This clone was found to contain three ORFs. The first ORF contains almost the entire ORF for CT694, a [0420] Chlamydia trachomatis (CT) specific hypothetical protein. The second ORF is a full length ORF for CT695, another hypothetical CT protein. The third ORF is the N-terminal portion of CT696.
Clone E9-D5-8 (identified using the patient lines CT10, CT1, CT4, and CT11) contains a 393 bp insert, which is disclosed in SEQ ID NO: 31. It was found to encode a partial ORF for CT680, the S2 ribosomal protein. [0421]
Clone E9-E10-51 (identified using the patient line CT10) contains an 883 bp insert, the sequence of which is disclosed in SEQ ID NO: 30. This clone contains two partial ORF. The first of these is for the C-terminal half of CT680, which may show some overlap with the insert present in clone E9-D5-8. The second ORF is the N-terminal partial ORF for CT679, which is the elongation factor TS. [0422]
Clone E3-B4-18 (identified using the CT1 patient line) contains a 1224 bp insert, the sequence of which is disclosed in SEQ ID NO: 29. This clone contains 4 ORFs. At the N-terminal end of the clone is the complete ORF for CT772, coding for inorganic pyrophosphatase. The second ORF is a small portion of the C-terminal end of CT771, on the complementary frame. The third is a partial ORF of the hypothetical protein, CT191 and the fourth is a partial ORF for CT190, DNA gyrase-B. [0423]
Clone E10-B2-57 (identified using the CT10 patient line) contains an 822 bp insert, the sequence of which is disclosed in SEQ ID NO: 42. This clone contains the complete ORF for CT066, a hypothetical protein, on the complementary strand. [0424]
Clone E3-F3-18 (identified using the CT1 patient line) contains an 1141 bp insert, the sequence of which is disclosed in SEQ ID NO: 41. It contains a partial ORF for pmpG (CT871) in frame with the 5-gal gene. [0425]
Clone E4-D6-21 (identified using the CT3 patient line) contains a 1297 bp insert, the sequence of which is disclosed in SEQ ID NO: 40. This clone contains a very small portion of xseA (CT329), the entire ORF for tpiS (CT328) on the complementary strand, and a partial amino terminal ORF for trpC (CT327) on the top frame. [0426]
Clone E1-G9-23 (identified using the CT3 patient line) contains an 1180 bp insert, the sequence of which is disclosed in SEQ ID NO: 39. This clone contains almost the entire ORF for glycogen synthase (CT798). [0427]
Clone E3-A3-31 (identified using the CT1 patient line) contains an 1834 bp insert, the sequence of which is disclosed in SEQ ID NO: 38. This clone contains a large region of the hypothetical gene CT622. [0428]
Clone E2-F7-11 (identified using both the CT3 and CT10 patient lines) contains a 2093 bp insert, the sequence of which is disclosed in SEQ ID NO: 37. This clone contains a large region of the rpoN gene (CT609) in frame with P-gal and the complete ORF for the hypothetical gene CT610 on the complementary strand. In addition, it also contains the carboxy-terminal end of CT611, another hypothetical gene. [0429]
Clone E7-H11-10 (identified using the CT3 patient line) contains a 1990 bp insert, the sequence of which is disclosed in SEQ ID NO: 36. This clone contains the amino terminal partial ORF for CT610, a complete ORF for CT611, another complete ORF for CT612, and a carboxy-terminal portion of CT613. All of these genes are hypothetical and all are present on the complementary strand. [0430]
Clone E10-C6-45 (identified using the CT3 patient line) contains a 196 bp insert, the sequence of which is disclosed in SEQ ID NO: 35. This clone contains a partial ORF for nrdA (CT827) in frame with 0-gal. This clone contains a relatively small insert and has particular utility in determining the epitope of this gene that contributes to the immunogenicity of Serovar E. [0431]
Clone E3-H6-10 (identified using the CT12 patient line) contains a 3734 bp insert, the sequence of which is disclosed in SEQ ID NO: 48. This clone contains ORFs for a series of hypothetical proteins. It contains the partial ORFs for CT223 and CT229 and the complete ORFs for CT224, CT225, CT226, CT227, and CT228. [0432]
Clone E4-C3-40 (identified using the CT10patient line) contains a 2044 bp insert, the sequence of which is disclosed in SEQ ID NO: 47. This clone contains a partial ORF for nrdA (CT827) and the complete ORF for nrdB (CT828). [0433]
Clone E2-D8-19 (identified using the CT1 patient line) contains a 2010 bp insert, the sequence of which is disclosed in SEQ ID NO: 46. This clone contains ORF from the [0434] Chlamydia trachomatis plasmid as well as containing partial ORFs for ORF3 and ORF6, and complete ORFs for ORF4 and ORF5.
Clone E3-D10-46 (identified using the patient lines CT1, CT3, CT4, CT11, and CT12) contains a 1666 bp insert, the sequence of which is identified in SEQ ID NO: 45. This clone contains a partial ORF for CT770 (fab F), a complete ORF for CT771 (hydrolase/phosphatase homologue), a complete ORF for CT772 (ppa, inorganic phosphatase), and a partial ORF for CT773 (Idh, Leucine dehydrogenase). [0435]
Clone E10-H8-1 (identified using both the CT3 and CT10 patient lines) contains an 1862 bp insert, the sequence of which is disclosed in SEQ ID NO: 44. It contains the partial ORFs for CT871 (pmpG) as well as CT872 (pmpH). [0436]
Clone E3-F3-7 (identified using the CT1 patient line) contains a 1643 bp insert, the sequence of which is identified in SEQ ID NO: 43. It contains the partial ORFs for both CT869 (pmpE) and CT870 (pmpF). [0437]

EXAMPLE 3

Additional CD4 T Cell Expression Cloning for the Identification of T Cell Stimulating Antigens from [0438] Chlamydia Trachomatis Serovar E
The T cell line CHH037 was generated from a 22 year-old healthy female sero-negative for Chlamydia. This line was used to screen the Chlamydia trachomatis serovar E library. Nineteen clones were identified from this screen, as described below. [0439]
Clone E7-B12-65, contains an 1179 bp insert, the sequence of which is disclosed in SEQ ID NO: 114. It contains the complete ORF of the gene for Malate dehydrogenase (CT376) on the complementary strand. [0440]
Clone E4-H9-83 contains a 772 bp insert, the sequence of which is identified in SEQ ID NO: 115. It contains the partial ORF for the heat shock protein GroEL (CT110). [0441]
Clone E9-B10-52 contains a 487 bp insert, the sequence of which is identified in SEQ ID NO: 116. It contains a partial ORF for the gene yscC (CT674), a general secretion pathway protein. [0442]
Clone E7-A7-79 contains a 1014 bp insert, the sequence of which is disclosed in SEQ ID NO: 117. It contains the complete ORF for the histone like development gene, hctA (CT743) and a partial ORF for the rRNA methyltransferase gene ygcA (CT742). [0443]
Clone E2-D11-18 contains a 287 bp insert, the sequence of which is disclosed in SEQ ID NO: 118. It contains the partial ORF for hctA (CT743). [0444]
Clone E9-H6-15, identified using the CT3 line, contains a 713 bp insert the sequence of which is disclosed in SEQ ID NO: 125. It contains the partial ORF of the pmpB gene (CT413). [0445]
Clone E3-D10-87, identified using the CT1 line, contains a 780 bp insert, the sequence of which is disclosed in SEQ ID NO: 126. It contains the partial ORF for CT388, a hypothetical gene, on the complementary strand, and a partial ORF for CT389, another hypothetical protein. [0446]
Clone E9-D6-43, identified using the CT3 line, contains a 433 bp insert, the sequence of which is disclosed in SEQ ID NO: 127. It contains a partial ORF for CT858. [0447]
Clone E3-D10-4, identified using the CT1 line, contains an 803 bp insert, the sequence of which is disclosed in SEQ ID NO: 128. It contains a partial ORF for pGP3-D, an ORF encoded on the plasmid pCHL1. [0448]
Clone E3-G8-7, identified using the CT1 line, contains an 842 bp insert, the sequence of which is disclosed in SEQ ID NO: 129. It contains partial ORFs for CT557 (Lpda) and CT558 (LipA). [0449]
Clone E3-F11-32, identified using the CT1 line, contains an 813 bp insert, the sequence of which is disclosed in SEQ ID NO: 130. It contains a partial ORF for pmpD (CT812). [0450]
Clone E2-F8-5, identified using the CT12 line, contains a 1947 bp insert, the sequence of which is disclosed in SEQ ID NO: 131. It contains a complete ORF for the 15 kDa ORF (CT442) and a partial ORF for the 60 kDa ORF (CT443). [0451]
Clone E2-G4-39, identified using the CT12 line, contains a 1278 bp insert, the sequence of which is disclosed in SEQ ID NO: 132. It contains the partial ORF of the 60kDa ORF (CT443). [0452]
Clone E9-D1-16, identified using the CT10 line, contains a 916 bp insert, the sequence of which is disclosed in SEQ ID NO: 133. It contains the partial ORF for the pmpH (CT872). [0453]
Clone E3-F3-6, identified using the CT1 line, contains a 751 bp insert, the sequence of which is disclosed in SEQ ID NO: 134. It contains the partial ORFs, all on he complementary strand, for genes accB (CT123), L13 ribosomal (CT125), and S9 ribosomal (CT126). [0454]
Clone E2-D4-70, identified using the CT12 line, contains a 410 bp insert, the sequence of which is disclosed in SEQ ID NO: 135. It contains the partial ORF for the pmpC gene (CT414). [0455]
Clone E5-A1-79, identified using the CT1 line, contains a 2719 bp insert, the sequence of which is disclosed in SEQ ID NO: 136. It contains a partial ORF for ydhO (CT127), a complete ORF for S9 ribosomal gene (CT126 on the complementary strand), a complete ORF for the L13 ribosomal gene (CT125 on the complementary strand) and a partial ORF for accC (CT124 on the complementary strand). [0456]
Clone E1-F7-16, identified using the lines CT12, CT3, and CT11, contains a 2354 bp insert, the sequence of which is disclosed in SEQ ID NO: 137. It contains a partial ORF of the ftsH gene (CT841) and the entire ORF for the pnp gene (CT842) on the complementary strand. [0457]
Clone E1-D8-62, identified using the CT12 line, contains an 898 bp insert, the sequence of which is disclosed in SEQ ID NO: 138. It contains partial ORFs for the ftsH gene (CT841) and for the pnp gene (CT842). [0458]

EXAMPLE 4

Expression of [0459] Chlamydia Tracomatis Recombinant Proteins
Several [0460] Chlamydia trachomatis serovar E specific genes were cloned into pET17b. This plasmid incorporates a 6× histidine tag at the N-terminal to allow for expression and purification of recombinant protein.
Two full-length recombinant proteins, CT622 and CT875, were expressed in [0461] E. coli. Both of these genes were identified using CtLGVII expression screening, but the serovar E homologues were expressed. The primers used to amplify these genes were based on serovar D sequences. The genes were amplified using serovar E genomic DNA as the template. Once amplified, the fragments were cloned in pET-17b with a N-terminal 6×-His Tag. After transforming the recombinant plasmid in XL-I blue cells, the DNA was prepared and the clones fully sequenced. The DNA was then transformed into the expression host BL21-pLysS cells (Novagen) for production of the recombinant proteins. The proteins were induced with IPTG and purified on Ni-NTA agarose using standard methods. The DNA sequences for CTE622 and CTE875 are disclosed in SEQ ID NO: 28 and 27 respectively, and their amino acid sequences are disclosed in SEQ ID NO: 140 and 139, respectively
Five additional [0462] Chlamydia trachomatis genes were cloned. The Chalmydia trachomatis specific protein CT694, the protein CT695, and the L1 ribosomal protein, the DNA sequences of which are disclosed in SEQ ID NO: 119, 120 and 121 respectively. The protein sequences of these 6×-histidine recombinant proteins are disclosed in SEQ ID NO: 122 (CT694), 123 (CT695), and 124 (L1 ribosomal protein). The genes CT875 and CT622, from serovar E were also cloned using pET17b as 6×-His fusion proteins. These recombinant proteins were expressed and purified and their the amino acid sequences disclosed in SEQ ID NO: 139 and 140, respectively.

EXAMPLE 5

Recombinant Chlamydial Antigens Recognized by T Cell Lines [0463]

Patient T cell lines were generated from the following donors: CT1, CT2, CT3, CT4, CT5, CT6, CT7, CT8, CT9, CT10, CT11, CT12, CT13, CT14, CT15, and CT16. A summary of their details is included in Table II.

TABLE II


C. trachomatis patients

			Clinical
Patients	Gender	Age	Manifestation	Serovar	IgG titer	Multiple Infections

CT1	M	27	NGU	LCR	Negative	No
CT2	M	24	NGU	D	Negative	E
CT3	M	43	Asymptomatic	J	Ct 1:512	No
			Shed Eb		Cp
			Dx was HPV		1:1024
					Cps
					1:256
CT4	F	25	Asymptomatic	J	Ct 1:1024	Y
			Shed Eb
CT5	F	27	BV	LCR	Ct 1:256	F/F
					Cp 1:256
CT6	M	26	Perinial rash	G	Cp	N
			Discharge,		1:1024
			dysuria
CT7	F	29	BV	E	Ct 1:512	N
			Genital ulcer		Cp
					1:1024
CT8	F	24	Not Known	LCR	Not	NA
					tested
CT9	M	24	asymptomatic	LCR	Ct 1:128	N
					Cp 1:128
CT10	F	20	Mild itch vulvar	negative	negative	12/1/98
CT11	F	21	BV	J	Ct 1:512	F/F/J/E/E
			Abnormal pap			PID 6/96
			smear
CT12	M	20	asymptomatic	LCR	Cp 1:512	N
CT13	F	18	BV, gonorrhea,	G	Ct 1:1024	N
			Ct vaginal
			discharge,
			dysuria
CT14	M	24	NGU	LCR	Ct 1:256	N
					Cp 1:256
CT15	F	21	Muco-purulint	culture	Ct 1:256	N
			cervicitis		Ct IgM
			Vaginal		1:320
			discharge		Cp 1:64
CT16	M	26	Asymptomatic/contact	LCR	NA	N
CL8	M	38	No clinical	negative	negative	No
			history of disease

PBMC were collected from a second series of donors and T cell lines have been generated from a sub-set of these. A summary of the details for three such T cell lines is listed in the table below. [0465]

TABLE III

Normal Donors

Donor Gender Age CT IgG Titer CP IgG Titer

CHH011 F 49 1:64 1:16

CHH037 F 22 0 0

CHH042 F 25 0 1:16
Donor CHH011 is a healthy 49 year old female donor sero-negaitve for [0466] C. trachomatis. PBMC produced higher quantities of IFN-gamma in response to C. trachomatis elementary bodies as compared to C. pneumoniae elementary bodies, indicating a C. trachomatis-specific response. Donor CHH037 is a 22 year old healthy female donor sero-negative for C. trachomatis. PBMC poruced higher quantities of IFN-gamma in response to C. trachomatis elementary bodies as compared to C. pneumoniae elementary bodies, indicating a C. trachomatis-specific response. CHH042 is a 25 year old healthy female donor with an IgG titer of 1:16 to C. pneumoniae. PBMC produced higher quantities of IFN-gamma in response to C. trachomatis elementary bodies as compared to C. pneumoniae elementary bodies, indicating a C. trachomatis-specific response.
Recombinant proteins for several [0467] Chlamydia trachomatis genes were generated as described above. Sequences for MOMP was derived from serovar F. The genes CT875, CT622, pmp-B-2, pmpA, and CT529 were derived from serovar E and sequences for the genes gro-EL, Swib, pmpD, pmpG, TSA, CT610, pmpC, pmpE, S13, lpdA, pmpI, and pmpH-C were derived from LII.

Several of the patient and donor lines described above were tested against the recombinant Chlamydia proteins. Table IV summarizes the results of the T cell responses to the recombinant Chlamydia proteins.

TABLE IV


Recombinant Chlamydia Antigens Recognized By T Cell Lines

CHH-

#of

CL8

CT10

CT1

CT3

CT4

CT5

CT11

CT12

CT13

011

037

Antigen

Serovar

hits

L2

E

L2

E

gro-EL

L2

10

−

+

(CT110)

MompF

F

10

−

+

(CT681)

CT875

E

8

−

+

−

+

−

+

SWIB

L2

8

+

−

+

−

+

−

+

(CT460)

pmpD

L2

5

−

+

−

+

−

(CT812)

pmpG

L2

6

−

+

−

+

nt

−

+

−

(CT871)

TSA

L2

6

−

+

−

+

−

+

(CT603)

CT622

E

3

−

+

−

+

−

+

−

CT610

L2

3

−

+

−

+

−

+

−

pmpB-2

E

3

−

+

−

(CT413)

pmpC

L2

4

−

+

−

+

−

+

−

+

(CT414)

pmpE

L2

3

−

+

−

+

−

(CT869)

S13

L2

2

+

−

+

−

(CT509)

1pdA

L2

3

−

+

−

+

−

(CT557)

pmpI

L2

2

−

+

−

+

−

(CT874)

pmpH-C

L2

1

−

+

−

(CT872)

pmpA

E

0

−

(CT412)

CT529

E

0

−

Although the present invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, changes and modifications can be carried out without departing from the scope of the invention which is intended to be limited only by the scope of the appended claims. [0469]
1 140 1 1311 DNA Chlamydia trachomatis 1 taattcgctt ttacctctct tcttgctgaa gacttggcta tgttttttat tttgacgata 60 aacctagtta aggcataaaa gagttgcgaa ggaagagccc taaacttttc ttatcatctt 120 ctttaactag gagtcatcca tgagtcaaaa taagaactct gctttcatgc agcctgtgaa 180 cgtatccgct gatttagctg ccatcgttgg tgcaggacct atgcctcgca cagagatcat 240 taagaaaatg tgggattaca ttaagaagaa tagccttcaa gatcctacaa acaaacgtaa 300 tatcaatccc gatgataaat tggctaaagt ttttggaact gaaaaaccta tcgatatgtt 360 ccaaatgaca aaaatggttt ctcaacacat cattaaataa aatagaaatt gactcacgtg 420 ttcctcgtct ttaagatgag gaactagttc attctttttg ttcgtttctg tgggtattac 480 tgtatcttta acaactatct tagcagcacc tgttttgaca tgggtttggg ccaatcactt 540 agagcctaac ctattgagag taacgcgttt aaattggaat ctgcctaaaa aatttgctca 600 tcttcatggg cttcgcatta tacagatttc ggatttacac ctaaaccact cgacgcctga 660 tgcctttcta aaaaaagtat ctcgtaagat ctcttctctt tctccagata ttcttgtatt 720 tacaggagac tttgtctgtc gcgctaaagt agaaactcct gaaagattaa aacatttcct 780 atgttctctg catgcgccct taggctgttt tgcttgccta ggaaatcatg attacgccac 840 ctacgtatcc cgtgatattc acgggaaaat taataccatc tcagcaatga atagccgtcc 900 tttaaaaaga gcttttacct ctgtttatca aagtctattc gcctcttctc gcaatgaatt 960 tgcagatact ctgaatccac aaattcctaa tccacaccta gtcagtatat tacgcaatac 1020 tccatttcaa ttattgcata atcaaagcgc gacactttcc gatacaatca acatcgtggg 1080 attaggcgat ttttttgcca aacaattcga tcccaaaaaa gcttttactg actataatcc 1140 cacgttacct ggtattatcc tttctcataa tcccgatacg attcaccatc tccaagatta 1200 cccaggtgat gttgtttttt ccgggcactc gcatggccct caaatctctc ttccctggcc 1260 taagtttgcc aatacgataa ccaataaact ttcagggtta gaaaacccag a 1311 2 1516 DNA Chlamydia trachomatis 2 tttgagctcg tgccgctcgt gccggtgcgt gtgaaccgct tcttcaaaag cttgtcttaa 60 aagatattgt ctcgcttccg gattagttac atgtttaaaa attgctagaa caatattatt 120 cccaaccaag ctctctgcgg tgctgaaaaa acctaaattc aaaagaatga ctcgccgctc 180 atcttcagaa agacgatccg acttccataa ttcgatgtct ttccccatgg ggatctctgt 240 agggagccag ttatttgcgc agccattcaa ataatgttcc caagcccatt tgtacttaat 300 aggaacaagt tggttgacat cgacctggtt gcagttcact agacgcttgc tatttagatt 360 aacgcgtttc tgttttccat ctaaaatatc tgcttgcata agaaccgtta attttattgt 420 taatttatat gattaattac tgacatgctt cacacccttc ttccaaagaa cagacaggtg 480 ctttcttcgc tctttcaaca ataattcctg ccgaagcaga cttattcttc atccaacgag 540 gctgaattcc tctcttatta atatctacaa aagatttttc aacggtcgtt gctgatgaag 600 atctcagata atacgtagtt ttcaaacctt ttttccaagc cgttaaatac atattcgaca 660 gttttttccc gtctggctgg gcaagataaa ggttgaggga ttgccccata tcaatccatt 720 tttgtcttcg agacgcgcat tcgataatcc attctggttc aatctcaaaa gctgtcaaga 780 aaatatgttt taagtgatct ggtatacgct cgatttccaa taaagaccca tcaaaatatt 840 tcaggtcatc taacatatca gcatcccaga tacctaattt cttcaacttc tcaattaaat 900 acacatttgg aatcgtgaat tctccggaca aattagactt cacaaacaaa tgtttgtacg 960 ttggctcaat agattgagtt actcctataa tgttggagat cgtcgctgtc ggagctatag 1020 ccataagctg acaatgtcgc ataccatgct ctttaaccaa actacggata ggttcccaat 1080 cttttcttga tgacgtatcc atctggagat ttgcttctcc tcgatagttc gctaacaact 1140 gaatcgtatc aatagggagc aaacctctat cccatttcga tcctttataa gagctgtaag 1200 tgcctcgttc tttagcgagc agacaagaag cttgaatcgc atagtaagaa atcaactctg 1260 aactgtagtc agcaaattct acagcttctt gcgaagcata gcttatatct agcttataca 1320 aggcatcttg gaatcccatc acccctaatc caatagcgcg gtgagcaaag ttcgcctctt 1380 tagcttcctt tgttggataa aagttaatat caatcacgtt atccaacata cggactgcta 1440 tagagatcgt ctcagagagt ttttcctcat caaacccatc ccctacgata tgttgaacta 1500 agttaatcga tcctaa 1516 3 2397 DNA Chlamydia trachomatis 3 agagtgtgct ggaggagcta tttttgcaaa acgggttcgt attgtagata accaagaggc 60 cgttgtattc tcgaacaact tctctgatat ttatggcggc gccattttta caggttctct 120 tcgagaagag gataagttag atgggcaaat ccctgaagtc ttgatctcag gcaatgcagg 180 ggatgttgtt ttttccggaa attcctcgaa gcgtgatgag catcttcctc atacaggtgg 240 gggagccatt tgtactcaaa atttgacgat ttctcagaat acagggaatg ttctgtttta 300 taacaacgtg gcctgttcgg gaggagctgt tcgtatagag gatcatggta atgttctttt 360 agaagctttt ggaggagata ttgtttttaa aggaaattct tctttcagag cacaaggatc 420 cgatgccatc tattttgcag gtaaagaatc gcatattaca gccctgaatg ctacggaagg 480 acatgctatt gttttccacg acgcattagt ttttgaaaat ctagaagaaa ggaaatctgc 540 tgaagtattg ttaatcaata gtcgagaaaa tccaggttca aaatttctca agtttgatgc 600 aattgtgcta ttcgctacct ttagttttct atgtccacgg taaagggatc ggaaagatac 660 gcatttattt tcatagtctt tagcttcgat ccctagtgct tccgcatgga ctcgtctgcc 720 aagacttttg gttacgaaaa caacaggctc tcgttgagaa atgatttgga gtagctctag 780 cgtgaggtgt tttttctgtt tctcgtggtt tgaaagattg actagaggag agacttcaat 840 acataactcg ctgccgtttt ttaataaaat ttgaccagag gagggtcttt ccgactgctc 900 tagtaataga cgaatattgc ccaatgctct ggaagcattt ttccctgatt catctcgaaa 960 ctttgcgcag gattccaatt cttcgattac tgtaaaaggg ataatgatgc gagtgttaga 1020 aaaagaggaa agggccttag gatcgtaaat caaaacgctg gtatcaataa cagaggtttt 1080 tttcattaca aattcctaaa tgactcaagt gtaaggggga gatagtactt tgattgtgta 1140 tcatatccag aaaaattaaa acatgtcttt gttagagaga agtcgggaga gagggttttt 1200 agcaatcaac ctccgcgtgt gctaatctgt ttgtcaaaaa tgtacccctt aactacaatg 1260 ccgaggaaag cgagtccttc tgttggaggt tgttatgaaa gtcaaaatta atgatcagtt 1320 catttgtatt tccccataca tttctgctcg atggaatcag atagctttca tagagtcttg 1380 tgatggaggg acggaagggg gtattacttt gaaactccat ttaattgatg gagagacagt 1440 ctctataccc aatctaggac aagcgattgt tgatgaggtg ttccaagagc acttgctata 1500 tttagagtcc acagctcctc agaaaaacaa ggaagaggaa aaaattagct ctttgttagg 1560 agctgttcaa caaatggcta aaggatgcga agtacaggtt ttttctcaaa agggcttggt 1620 ttctatgtta ctaggaggag ctggttcgat taatatgttg ttgcaacatt ctccagaaca 1680 taaggatcat cctgatcttc ctaccgattt actggagagg atagcgcaaa tgatgcgttc 1740 attatctata ggaccaactt ctattttagc taagccagag cctcattgca actgtttgca 1800 ttgtcaaatt ggacgagcta cagtggaaga agaggatgcc ggagtatcgg atgaggatct 1860 cacttttcgt tcatgggata tctctcaaag tggagaaaag atgtacactg ttacagatcc 1920 tttgaatcca gaagtatacc ttttgttttt tttatacgag ccagcactcc aatttctgac 1980 tgtgagaata tatcataaat agaccggcct ctagcgctgc gaatagaaaa agtctttgct 2040 atagcactat caagccttcc ctttatacgc tcaagcaata gaaacggaga tctacgcaat 2100 ggattttcat tgtactcatt aaacgagcgg aaaatgaaat tactcaaatt ttcttcagcg 2160 ctacacacgc tcaaatcatc gaggaaaacc gtatgagaaa cggatctact cgtgccgaat 2220 tcggcacgag gtctctaatc ttgcagaagg agcacaaatt tttgctgtcc aagggttaaa 2280 tactgctgga gaaataggat actgccctcc ttgccctcca gatgcgaagc atcgctatta 2340 cttttatgct tatgcgctcg atgttgtgct ttccgatgaa gaaggagtga ccaaaga 2397 4 1094 DNA Chlamydia trachomatis 4 tgatgcagaa gacactgtta agaagttaca agaagccggt gctaaggctg ttgctaaagg 60 gctgtaattg ttatgggaaa gagaatgctt tgggggttgc ttgcaagctt ctcttttcgt 120 ttagctgcac agtagctggg cacagagggg ttcccggtac gtcttaacag atttgtctgg 180 acttaacttt tagtgtttgg catcgcaaac agaatatttc tgttgcaatg gttttttctt 240 aatggaatca aggtgatagt atttgtcgga tggacaagtg tatagagagt atccagtgtc 300 tctgtattgg atagactctg ttttgtccta gctggaaagc atctgtcgta ttcctgttta 360 gagatcacag agggactaaa tagggaaatg gtatcgccaa aagtcttaaa gtcttaggag 420 agctcgcatg ttcaagtgcc cggagcgggt cagcgtcaaa aagaaagaag atattttaga 480 tcttcctaat cttgtcgaag ttcaaatcaa gtcgtataag cagtttcttc aaatcgggaa 540 gcttgctgaa gagcgagaaa acattggttt agaagaagtc ttcagagaaa ttttccctat 600 caagtcttat aatgaagcta cgattttaga gtacctctct tataacttag gagtgcccaa 660 atactcccca gaagagtgta ttcgtcgggg aatcacctat agtgttactt taaaggttcg 720 tttccgttta actgatgaaa cggggattaa agaagaagaa gtctatatgg gaaccatccc 780 catcatgact cataagggaa cctttattat taatggggca gagagagtcg ttgtttctca 840 agtccaccgt tctccaggaa tcaattttga acaagaaaaa cattctaaag ggaatgtttt 900 attttctttt agaattattc cttatcgagg aagttggtta gaagctgtct tcgacattaa 960 tgaccttatc tatatccata ttgataggaa aaaacgtcgc agaaagattt tagctattga 1020 cgtttatccg agctttagga tattcaacag atgcagatat tattgaagag ttcttttctg 1080 tagaggagcg ttcc 1094 5 2129 DNA Chlamydia trachomatis 5 gcttctttaa gagataagca acaaccgagg aatccactcc tccagacata gcaacaatga 60 tagttttacg cacaatgagc ccagaaaacg ctttcgttta ttgaagtttg cacattacaa 120 agggccatca tgttagcaaa aaaacaggat caaaaaaacc tatttctcaa gccgcctctt 180 ttaaatctta attacaaaaa taaaaatcaa ttcaactttt caaaaaaaga atttaaacat 240 taattgttat aaaaacaata tttattataa aataataacc atagttgcgg ggaaatctct 300 ttcatggttt attttagagc tcatcaacct aggcatacgc ctaaaacatt tcctttggaa 360 gttcaccatt cgttctccga taagcatcct caaattgcta aagctatgcg gattacgggg 420 ataaccctcg cagctctatc tctgctcgct gtagtcgcct gcgttattgc cgtctctgcg 480 ggaggagctg ccattcctct tgctgtcatt ggtggaattg ctgcaatgtc tggcctctta 540 tccgctgcca ccattatctg ttctgcaaaa aaggctctgg ctcaacgaaa acaaaaacaa 600 ctagaagagt tgcttccgtt agataatgcg accgagcatg tgaattacct gacctcagac 660 acctcttatt ttaatcaatg ggaatcctta gatgctctaa ataagcagtt gtctcagatt 720 gacttaacta ttcaagctcc cgaaaaaaaa ctattaaaag aagttcttgg ttccagatac 780 gattccatta atcactccat cgaagagatc tccgatcgct ttacgaaaat gctctctctt 840 cttcgattaa gagaacattt ttgtcgagga gaagagcgtt atgcccccta tttaagccct 900 cctctactta acaagaatcg tttgctgacc caaatcacat ccaatatgat taggatgcta 960 ccaaaatccg gtggtgtttt ttccctcaaa gccaatacac taagtcatgc cagccgcaca 1020 ctatatacag tattgaaagt cgctttatcc ttaggagttc tcgctggagt cgctgctctt 1080 atcatctttc ttccccctag cctgcctttt atcgctgtta taggagtatc ttccttagca 1140 ttggggatgg catctttcct tatgattcgg ggcattaagt atttgctcga acattctcct 1200 ctgaatagaa agcaattagc taaagatatt caaaaaacca ttatcccaga tgtcttggcc 1260 tctatggttc attaccagca tcaattacta tcacatctac atgaaactct attagatgaa 1320 gccatcacag ctagatggag cgagcccttc tttattgaac acgctaatct taaggcaaaa 1380 attgaagatt tgacaaaaca atatgatata ttgaacgcag cctttaataa atctttacaa 1440 caagatgagg cgctccgttc tcaattagag aaacgagctt acttattccc aattcctaat 1500 aacgacgaaa atgctaaaac taaagaatcg cagcttctag actcagaaaa tgattcaaat 1560 tctgaatttc aggagattat aaataaagga ctagaagctg ccaataaacg acgagctgac 1620 gctaagtcaa aattctatac ggaagacgaa acctctgaca aaagattctc tatatggaaa 1680 cccacaaaga acttggcatt agaagatttg tggagagtgc atgaagcttg caatgaagag 1740 caacaagctc tcctcttaga agattatatg agttataaaa cctcagaatg tcaagctgca 1800 ctccaaaaag tgagtcaaga actgaaggcg gcacaaaaat cattcgcagt cctagaaaag 1860 catgctctag acagatctta tgaatccagt gtagccatga tggatttagc tagagcgaat 1920 caagaaacac accggcttct gaacatcctc tctgaattac aacaactagc acaatacctg 1980 ttagataatc actaacggtt cttcataaat gacaaaaaga aaaaggagag ctgttgctgt 2040 gctctccttt ttctctaaat attcctgaaa gactaacctt tttatggttg cgttgagcct 2100 cctcctcctg ttcccgagga gcccgcaac 2129 6 1828 DNA Chlamydia trachomatis 6 gagggagcag cctaactctc ccctctcttc ttaaaaaaga ggggagcctt ttttccttac 60 aaagatacgc tagctttttc ctgaagaatc tcatcaagag atatttgcat tttcccacgg 120 ataaaggcat cccaaggaag ccctggaatc acttcatatt ctcccgttgc tagcattcga 180 caagggaaac caaagattaa atcttccggt aatccatagg gattgtggtc cgaacacact 240 ccggaagaaa accattctcc ttcttttggc tgatatattg atcgagcagc ctctgctaaa 300 gctcgtgctg cagaagctgc cgaagacttc cctcgtgctt cgattactgc actaccacga 360 ctctgtacag aaggcaccat aatattctct aaccaatcac gatccgctat cgtctctgcg 420 ataggacggt cattaatcag agcttgcgta aaatcaggca cttgtttggc ggagtgattt 480 ccccaaacca caacttgtga tacagccgat aaaggtactt ctgctctatg cgataacatg 540 ctatgcatac gattctggtc caatcgtagc atcgcatgaa agttctttct caataatctg 600 ggagcatgat tcattgctat ccagcaattg gtattcacag ggttcccaac aacaaaaatc 660 tttgcatccc gcttggctgt tgtgttcaaa gcttttcctt gcgtagcaaa aatctcccca 720 tttttcttta gaagatccct tctctccatt cctgggcctc taggaactga ccctataagg 780 aatgccgcat caatgccatc aaaagcatca tgcaatgatg tcgttacctg cacacgctgt 840 aataaaggga aagcaccatc atctagctcc atgcgcacac cagataaagc cctttctgtt 900 ccaggaatat cgtagatacg cagatcgatg ccacaatcaa ggccaaaaac atctccatga 960 gccagagaaa atagaaagct ataggctatt tgccctgttc ctcctgttac tgctacactc 1020 actgtttgag aaaccataag ccaccctctc tttactttta caaaacgcac atactctcaa 1080 cactacgttt gcaactaact aattttggtc ccaacatacg tttggatgat aaaagaatca 1140 agtacctaga ttccttagta aaagcttttg gcaaaaaaaa gctcatctat ttttcaatag 1200 atgagccgac tttaactgaa taagaactta gaaaacttta taaaaaatag gcccgtgtga 1260 tcctacccat atacttgatc ccgaccgcat aacttgttgt ccctttttag cagccaaata 1320 accgtggaca tctaaaaaac caataaaccg tgcgcgaata aagaacataa agcccctaaa 1380 aaaacgattt taagagagaa gtaatagaca gattgtaaca tatttaaaat aaaaactctg 1440 caaacaaaaa aactttgcct ggccgtctcc gtagaaagca ctttatgtta aaacgttaaa 1500 aagtcttaac atacctcgag cttcgggaaa ctctacagga gcattccccg acatgatgcc 1560 tataatttgc gttgccaatt ctttccctaa tgaaacccct tcttgatcaa aagaattgat 1620 tccccagcaa aacccttgaa atgcaaattt atgctcataa aaagccaata aactaccagc 1680 aatacgagga gaaagctgtt gcgctaccaa tatcgaagaa ggtctgttcc ctttaaacct 1740 cttattcggg ttcgcattat ctctaccctg agctaaagct aaagattgag caacaaggtt 1800 tgcaaagagc ttttgagatc tcgtgccg 1828 7 861 DNA Chlamydia trachomatis 7 gggcgcacta ctttaaagat tcgtcgtcct tttggtacta cgagagaagt tcgtgtgaaa 60 tggcgttatg ttcctgaagg tgtaggagat ttggctacca tagctccttc tatcagggct 120 ccacagttac agaaatcgat gagaagcttt ttccctaaga aagatgatgc gtttcatcgg 180 tctagttcgc tattctactc tccaatggtt ccgcattttt gggcagagct tcgcaatcat 240 tatgcaacga gtggtttgaa aagcgggtac aatattggga gtaccgatgg gtttctccct 300 gtcattgggc ctgttatatg ggagtcggag ggtcttttcc gcgcttatat ttcttcggtg 360 actgatgggg atggtaagag ccataaagta ggatttctaa gaattcctac atatagttgg 420 caggacatgg aagattttga tccttcagga ccgcctcctt gggaagaatt tgctaagatt 480 attcaagtat tttcttctaa tacagaagct ttgattatcg accaaacgaa caacccaggt 540 ggtagtgtcc tttatcttta tgcactgctt tccatgttga cagaccgtcc tttagaactt 600 cctaaacata gaatgattct gactcaggat gaagtggttg atgctttaga ttggttaacc 660 ctgttggaaa acgtagacac aaacgtggag tctcgccttg ctctgggaga caacatggaa 720 ggatatactg tggatctaca ggttgccgag tatttaaaaa gctttggacg tcaagtattg 780 aattgttgga gtaaagggga tatcgagtta tcaacgccta ttcctctttt tggttttgag 840 aagattcatc cacatcctcg a 861 8 763 DNA Chlamydia trachomatis 8 ataacaaaaa catcttgatt atttttgtta aaagaaatac ttaatgagtt ttatttaatt 60 aacgaaacga aaagcttgct aatgaaaatt attcacacag ctatcgaatt tgctccggta 120 atcaaagccg gaggcctggg agacgcgcta tacggactag caaaagcttt agccgctaat 180 cacacaacgg aagtggtaat ccctttatac cctaaattat ttactttgcc caaagaacaa 240 gatctttgct cgatccaaaa attatcttat ttttttgctg gagagcaaga agcaactgct 300 ttctcctact tttatgaagg aattaaagta actctattca aactcgacac acagccagag 360 ttattcgaga atgcggaaac aatctacaca agcgatgatg ccttccgttt ttgcgctttt 420 tctgctgctg cggcctccta catccaaaaa gaaggagcca atatcgttca tttacacgat 480 tggcatacag gattagttgc tggactactc aaacaacagc cctgctctca attacaaaag 540 attgttctta ccctacataa ttttggttat cgaggctata caacacgaga aatattagaa 600 gcctcctctt tgaatgaatt ttatatcagc cagtaccaac tatttcgcga tccacaaact 660 tgtgtgttgc taaaaggagc tttatactgt tcagatttcg tgactacggt ttctcctaca 720 tacgccaaag aaattcttga agattattcc gattacgaaa ttc 763 9 665 DNA Chlamydia trachomatis 9 ttgaaactaa aaacctaatt tatttaaagc tcaaaataaa aaagagtttt aaaatgggaa 60 attctggttt ttatttgtat aacactgaaa actgcgtctt tgctgataat atcaaagttg 120 ggcaaatgac agagccgctc aaggaccagc aaataatcct tgggacaaca tcaacacctg 180 tcgcagccaa aatgacagct tctgatggaa tatctttaac agtctccaat aattcatcaa 240 ccaatgcttc tattacaatt ggtttggatg cggaaaaagc ttaccagctt attctagaaa 300 agttgggaga tcaaattctt gatggaattg ctgatactat tgttgatagt acagtccaag 360 atattttaga caaaatcaaa acagaccctt ctctaggttt gttgaaagct tttaacaact 420 ttccaatcac taataaaatt caatgcaacg ggttattcac tcccagtaac attgaaactt 480 tattaggagg aactgaaata ggaaaattca cagtcacacc caaaagctct gggagcatgt 540 tcttagtctc agcagatatt attgcatcaa gaatggaagg cggcgttgtt ctagctttgg 600 tacgagaagg tgattctaag ccctgcgcga ttagttatgg atactcatca ggcattccta 660 attta 665 10 843 DNA Chlamydia trachomatis 10 tgggaatgtc gaagaatacg attacgttct cgtatctata ggacgccgtt tgaatacaga 60 aaatattggc ttggataaag ctggtgttat ttgtgatgaa cgcggagtca tccctaccga 120 tgccacaatg cgcacaaacg tacctaacat ttatgctatt ggagatatca caggaaaatg 180 gcaacttgcc catgtagctt ctcatcaagg aatcattgca gcacggaata tagctggcca 240 taaagaggaa atcgattact ctgccgtccc ttctgtgatc tttaccttcc ctgaagtcgc 300 ttcagtaggc ctctccccaa cagcagctca acaacaaaaa atccccgtca aagtaacaaa 360 attcccattt cgagctattg gaaaagcggt cgcaatgggc gaggccgatg gatttgcagc 420 cattatcagc catgagacta ctcagcagat cctaggagct tatgtgattg gccctcatgc 480 ctcatcactg atttccgaaa ttaccctagc agttcgtaat gaactgactc ttccttgtat 540 ttacgaaact atccacgcac atccaacctt agcagaagtt tgggctgaaa gtgcgttgtt 600 agctgctgat accccattac atatgccccc tgctaaaaaa tgaccgattc agaatctcct 660 actcctaaaa aatctatacc cgccagattc cctaagtggc tacgccagaa actcccttta 720 gggcgggtat ttgctcaaac tgataatact atcaaaaata aagggcttcc tacagtctgt 780 gaggaagcct cttgtccgaa tcgcacccat tgttggtcta gacatacagc gtacctatct 840 agc 843 11 1474 DNA Chlamydia trachomatis 11 acagaaggga cggcagagta atcgatttcc tctttatggc cagctatatt ccgtgctgca 60 atgattcctt gatgagaagc tacatgggca agttgccatt ttcctgtgat atctccaata 120 gcataaatgt taggtacgtt tgtgcgcatt gtggcatcgg tagggatgac tccgcgttca 180 tcacaaataa caccagcttt atccaagcca atattttctg tattcaaacg gcgtcctata 240 gatacgagaa cgtaatcgta ttcttcgaca ttcccattga tagttaaccg aacgcgatct 300 cctatatcct caatatttga tacagaggct tctagtacga aacggagtcc ttgtcgggtg 360 aatttatcga acatggtttt tgaaatatct ggattattca aagcaaggat ttgagagctt 420 gcttcgatca cagaaacttc ggagcctaac gtatggaata aggaagcgaa ttcgcaaccg 480 atcacaccac cgccaataat ggccattttt tgagggattt ctttgaggtt tagcacgcct 540 gttgagcata aaatccgagg agattctgcg gaaaaaggaa tcccggggaa agctcgtggt 600 tcagagccgg tggctaggat aatggagtgc gctttgatta cagaagggtt ttctcctaag 660 atttttactt ctgttgaaga gatcaaagag cctcttccag agaagacagt gatcttattg 720 ctgcgaatga gaccattaag tccatcgcgg atgctacgga ctacggaatc cttcctttgt 780 accatagcgg gatagttgat gctgaatcct tctacatgaa tcccaaactg gtcagcatgg 840 cgtatttggg taacgacttc agctcctgct aagagggctt tagaaggaat acaccctcgg 900 tttaaacagg ttccgccagc ctctcgcttt tcgattagcg cagttttgag tcctgcttga 960 gcggcagtga ttgctgcaac atagcctcct ggccccgctc cgataactac acagtcgaaa 1020 gcttcattca taacatttcc tcttcaatga gtgtttagga ttgcaacgat ccatatgaga 1080 tgattatctg aaggaagagg attctccttc caagcctttc taggaaaggg aaagagaggt 1140 ccttcagaca aatacatttc ccggattgta catctgggtg gataaaatct caatgaggag 1200 aagtggtagc aggagagaaa aaataggaac gtaagagtgt tatttcgaat gctcagggag 1260 agagcggtac ccacgataag caagcagaat cccgactagt gcatagatgt atgagcgatt 1320 ctttggccag gagagaacga gtccagagcc tgtcgaaaac aagagaatca tgagcgaaaa 1380 ggtaaggaaa ccgcaaccca agaagagagc tgcagtcggc caatattgta gccagtccca 1440 ctgggagggg gcaggctctt gaacaggctc ctca 1474 12 2017 DNA Chlamydia trachomatis 12 ataagcattc tcatctaccc agaagtagaa gtcaaaacct tcataagtat ctaaaaagac 60 tcgcatataa tcttcgatac catccggagg cgctcctgcg atccatattc catggatgat 120 tttctcaaca ggtacacgat ggcctttaaa ttctgttttg atggtttcaa gaacaccttc 180 aatcggagtc gtcttaggtt tttcttcggc tttctgttcc ttagcttttg cctgtttagg 240 ctgagcctgc gatgatgctg gaagcttctt ctgaatggca tcgacgtatt ttccttgttg 300 aatcaaggaa ttctgtcccg cttccgaatt tttatctggc atagagttgt aagcactaat 360 gacctttttc agtttattta ataggtcttt aacagtagat ttctgttcag gagtaattcc 420 tagtttttct tctatgttct tgggagtaag atcgtatttg ctagcatcaa gattttctat 480 ctttccagaa gaagcttcct ccttcttctc ttctatagca cgcttttttc tcgataaaac 540 agctgctgta ggaggaactg cactagcaga aatcgttttt accccccccc ctctgaacag 600 agtacgtacg aacgttcact ggctgtgtaa taaacttcgt ctttctctta cgaggagagg 660 ttttgtcgtt acttcctgtt ctttagagat tgtagtgacc ttattctctg aagtagaagt 720 ctctgccgtc tcgtgccgaa ttcggcacga gaagccatgt tatctttgct tagatcaatg 780 ccttcttgtt ttttgaattc atcaagcatc cagttgatga tgactccgtc gaagtcgtct 840 cctcccaagt gagtatcccc gttggttgag agaacttcaa aaactccgtc accgatttcc 900 aagatagaaa tatcgaaagt tcctcctcct aagtcgaaga cggcgatttt tttatctcct 960 tccttatcaa taccataagc aagagcggcc gctgttggtt caggaataat gcgtttaaca 1020 tctaatcctg cgatacgtcc agcatctttt gtagaagctc tttgagaatc gttaaagtaa 1080 gctggtacgg taatgactgc ttccgttact gtttctccga gataagcctc agcagtttcc 1140 ttcatcttca tgaggatctg agcgccgatt tcttctggag tgtacagttt ttgttccaca 1200 tcaaagaccg catctccttt cgagttagga gcaactttgt aggggactgt tttaatttca 1260 gattcgactt cagagaattt tctaccgatg aatcgcttag tagaagccaa tgttttttca 1320 ggattggtta ctgcctgacg ttttgcagga attccaacaa gagtttcgcc acctttaaaa 1380 gcaacgatag aaggagtagt acgagttcct tcagaagagg caataacttt aggttggcca 1440 ccttccataa cagagacgca agagttggtc gtccctaggt cgataccaat aattttgtta 1500 gactttcttt tttcgctcat attgaacacc taatttctag gataattatt ctttttcttc 1560 gttaccgtct gagtttcctt tagcaggaag ttttgctact ttcactttgg ctacgcgaat 1620 aggacgatct cctatcttat aacctttagt aaattcctcc aagatagtcc cttctggaat 1680 tgttgtggtt tcttcgattt ctacagcttc atgcaggtac ggattaaata gttctccttt 1740 cgaggaatat tcaaccacac ctttctcttc gaagatttgc ttaaattgtt gaaggatcat 1800 ttggaatcct atagcccaat tttttacttc ttcagaggtt tgagaagcga atcccaaagc 1860 cttttccata ctttcgatag aaggaaggaa atccataaga gcattttcta cagcatactg 1920 catcatttct gtgcgttctt tctgtagtcg ttttcttgag ttttctgctt cagcgagagc 1980 catcagatat cgatcattct gttcttgcct cgtgccg 2017 13 1171 DNA Chlamydia trachomatis 13 ggtaaacgag ttaaaacaag agcatacagg gctaacggac tcgcctttag tgaaaaaagc 60 tgaggagcag attagtcaag cacaaaaaga tattcaagag atcaaaccta gtggttcgga 120 tattcctatc gttggtccga gtgggtcagc tgcttccgca ggaagtgcgg caggagcgtt 180 gaaatcctct aacaattcag gaagaatttc cttgttgctt gatgatgtag acaatgaaat 240 ggcagcgatt gcactgcaag gttttcgatc tatgatcgaa caatttaatg taaacaatcc 300 tgcaacagct aaagagctac aagctatgga ggctcagctg actgcgatgt cagatcaact 360 ggttggtgcg gatggcgagc tcccagccga aatacaagca atcaaagatg ctcttgcgca 420 agctttgaaa caaccatcag cagatggttt ggctacagct atgggacaag tggcttttgc 480 agctgccaag gttggaggag gctccgcagg aacagctggc actgtccaga tgaatgtaaa 540 acagctttac aagacagcgt tttcttcgac ttcttccagc tcttatgcag cagcactttc 600 cgatggatat tctgcttaca aaacactgaa ctctttatat tccgaaagca gaagcggcgt 660 gcagtcagct attagtcaaa ctgcaaatcc cgcgctttcc agaagcgttt ctcgttctgg 720 catagaaagt caaggacgca gtgcagatgc tagccaaaga gcagcagaaa ctattgtcag 780 agatagccaa acgttaggtg atgtatatag ccgcttacag gttctggatt ctttgatgtc 840 tacgattgtg agcaatccgc aagcaaatca agaagagatt atgcagaagc tcacggcatc 900 tattagcaaa gctccacaat ttgggtatcc tgctgttcag aattctgcgg atagcttgca 960 gaagtttgct gcgcaattgg aaagagagtt tgttgatggg gaacgtagtc tcgcagaatc 1020 tcaagagaat gcgtttagaa aacagcccgc tttcattcaa caggtgttgg taaacattgc 1080 ttctctattc tctggttatc tttcttaacg tgtgattgaa gtttgtgaat gagggggagc 1140 caaaaaagaa tttctttttt ggctcttttt t 1171 14 877 DNA Chlamydia trachomatis 14 cagagaattc tcgacatact atctaatcgg atatgtaaag ctgctttaca tcccttgaac 60 tagaaataaa atggaaataa aaagcccaga acaagagaag ttgttctggg ctgacagaag 120 ctgtcagatc attttaataa gattgatgac aactacgaca agttcctgga tccaaaaaag 180 aatctaaaaa gccatacaaa gattgcgtta cttcttgcga tgcctctaac actttatcag 240 cgtcatcttt gagaagcatc tcaatgagcg ctttttcttc tctagcatgc cgcacatccg 300 cttcttcatg ttctgtgaaa tatgcatagt cttcaggatt ggaaaatcca aagtactcag 360 tcaatccacg aattttctct ctagcgatac gtggaatttg actctcataa gaatacaaag 420 cagccactcc tgcagctaaa gaatctcctg tacaccaccg cacgaaagta gctactttcg 480 cttttgctgc ttcactaggc tcatgagcct ctaactcttc tggagtaact cctagagcaa 540 acacaaactg cttccacaaa tcaatatgat tagggtaacc gttctcttca tccatcaagt 600 tatctaacaa taacttacgc gcctctaaat catcgcaacg actatgaatc gcagataaat 660 atttaggaaa ggctttgata tgtaaataat agtctttggc atacgcctgt aattgctctt 720 tagtaagctc ccccttcgac catttcacat aaaacgtgtg ttctagcata tgcttatttt 780 gaataattaa atctaactga tctaaaaaat tcataaacac ctccatcatt tcttttcttg 840 actccacgta accgcttgca aaaaaggtcc gtataag 877 15 396 DNA Chlamydia trachomatis serovar E 15 tgtaccaaat atgagcttag atcaatctgt tgttgaactt tacacagata ctgccttctc 60 ttggagcgtg ggcgctcgag cagctttgtg ggagtgcgga tgtgcgactt taggggcttc 120 tttccaatac gctcaatcta aacctaaagt cgaagaatta aacgttctct gtaacgcagc 180 tgagtttact atcaataagc ctaaaggata tgtagggcaa gaattccctc ttgcactcat 240 agcaggaact gatgcagcga cgggcactaa agatgcctct attgattacc atgagtggca 300 agcaagttta gctctctctt acagattgaa tatgttcact ccctacattg gagttaaatg 360 gtctcgagca agttttgatg ccgatacgat tcgtat 396 16 516 DNA Chlamydia trachomatis serovar E 16 ctcaaaattt gacgatttct cagaatacag ggaatgttct gttttataac aacgtggcct 60 gttcgggagg agctgttcgt atagaggatc atggtaatgt tcttttagaa gcttttggag 120 gagatattgt ttttaaagga aattcttctt tcagagcaca aggatccgat gccatctatt 180 ttgcaggtaa agaatcgcat attacagccc tgaatgctac ggaaggacat gctattgttt 240 tccacgacgc attagttttt gaaaatctag aagaaaggaa atctgctgaa gtattgttaa 300 tcaatagtcg agaaaatcca ggttacactg gatctattcg atttttagaa gcagaaagta 360 aagttcctca atgtattcat gtacaacaag gaagccttga gttgctaaat ggagctacat 420 tatgtagtta tggttttaaa caagatgctg gagctaagtt ggtattggct tctggatcta 480 aactgaagat tttagattca ggaactcctg tacaag 516 17 723 DNA Chlamydia trachomatis serovar E 17 ctccttttaa gggggacgat gtttacttga atggagactg cgcttttgtc aatgtctatg 60 caggggcaga gaacggctca attatctcag ctaatggcga caatttaacg attaccggac 120 aaaaccatac attatcattt acagattctc aagggccagt tcttcaaaat tatgccttca 180 tttcagcagg agagacactt actctgaaag atttttcgag tttgatgttc tcgaaaaatg 240 tttcttgcgg agaaaaggga atgatctcag ggaaaaccgt gagtatttcc ggagcaggcg 300 aagtgatttt ttgggataac tctgtggggt attctccttt gtctattgtg ccagcatcga 360 ctccaactcc tccagcacca gcaccagctc ctgctgcttc aagctcttta tctccaacag 420 ttagtgatgc tcggaaaggg tctatttttt ctgtagagac tagtttggag atctcaggcg 480 tcaaaaaagg ggtcatgttc gataataatg ccgggaattt tggaacagtt tttcgaggta 540 atagtaataa taatgctggt agtgggggta gtgggtctgc tacaacacca agttttacag 600 ttaaaaactg taaagggaaa gtttctttca cagataacgt agcctcctgt ggaggcggag 660 tagtctacaa aggaactgtg cttttcaaag acaatgaagg aggcatattc ttccgaggga 720 aca 723 18 1377 DNA Chlamydia trachomatis serovar E 18 aaacagctaa tcgtcactac gctcacgtgg actgccctgg tcacgctgac tatgttaaaa 60 acatgatcac cggtgcggct caaatggacg gggctattct agtagtttct gcaacagacg 120 gagctatgcc tcaaactaaa gagcatattc ttttggcaag acaagttggg gttccttaca 180 tcgttgtttt tctcaataaa attgacatga tttccgaaga agacgctgaa ttggtcgact 240 tggttgagat ggagttggct gagcttcttg aagagaaagg atacaaaggg tgtccaatca 300 tcagaggttc tgctctgaaa gctttggaag gggatgctgc atacatagag aaagttcgag 360 agctaatgca agccgtcgat gataatatcc ctactccaga aagagaaatt gacaagcctt 420 tcttaatgcc tattgaggac gtgttctcta tctccggacg aggaactgta gtaactggac 480 gtattgagcg tggaattgtt aaagtttccg ataaagttca gttggtcggt cttagagata 540 ctaaagaaac gattgttact ggggttgaaa tgttcagaaa agaactccca gaaggtcgtg 600 caggagagaa cgttggattg ctcctcagag gtattggtaa gaacgatgtg gaaagaggaa 660 tggttgtttg cttgccaaac agtgttaaac ctcatacaca gtttaagtgt gctgtttacg 720 ttctgcaaaa agaagaaggt ggacgacata agcctttctt cacaggatat agacctcaat 780 tcttcttccg tacaacagac gttacaggtg tggtaactct gcctgaggga gttgagatgg 840 tcatgcctgg ggataacgtt gagtttgaag tgcaattgat tagccctgtg gctttagaag 900 aaggtatgag atttgcgatt cgtgaaggtg gtcgtacaat cggtgctgga actatttcta 960 agatcattgc ataaattaag tgatgtgttg gcgaggctga aaagccttgc ctttgggtgt 1020 gtagcttaga tggtagagca gtggcctcca aagccgccgg tcgggggttc gaatccctcc 1080 gcactcgtat taggtaactg aaagaagaat tcgcttatgg ggcaagatca ccgaagaaaa 1140 tttcttaaga aagtatcttt tgcaaaaaaa caagcagctt ttgcgggtaa ctttatcgaa 1200 gaaattaaga agattgagtg ggtaaataag cgaaatctta aaagatacgt caagattgtt 1260 ttgatgaata tttttggctt tggattttcc atctattgtg tggatttagc tcttcgaaag 1320 tccctttcat tgttcggtaa agtaacaagc tttttctttg gttgattcat gtttaag 1377 19 1736 DNA Chlamydia trachomatis serovar E 19 gtagcggaac aaagccggac cacgaggcct catagaatat aaaaatacga ggagcttaaa 60 catgtcagat caagcaacga ccctcaagat taaacctttg ggagatagaa ttttagttaa 120 aagagaagaa gaagcttcca ctgcaagagg cggaatcatt cttcctgaca ctgccaagaa 180 aaagcaagat agagctgaag ttttagctct aggaacaggc aaaaaagatg ataaagggca 240 gcaacttcct tttgaagttc aggttggtga catcgtttta attgataaat attctggcca 300 agaactcact gtagaaggtg aagagtacgt catcgttcaa atgagcgaag ttatcgcagt 360 tctgcaataa aaactaagag agtgaagtaa gatttaaggg agcgcatcaa tggtcgctaa 420 aaacattaaa tacaacgaag aagccagaaa gaaaattcaa aaaggagtta agactttagc 480 tgaagctgta aaagtcactc tagggcctaa aggacgacat gttgtcatag ataaaagctt 540 cggatcccct caagtaacta aagatggtgt taccgttgcg aaagaagttg agcttgccga 600 caaacatgaa aatatgggcg ctcaaatggt caaagaagtc gccagcaaaa ctgctgacaa 660 agctggagac ggaactacaa cagctactgt tcttgctgaa gctatctata cagaaggatt 720 acgcaatgta acagctggag caaatccaat ggacctcaaa cgaggtattg ataaagctgt 780 taaggttgtt gttgatcaaa tcagaaaaat cagcaaacct gttcagcatc ataaagaaat 840 tgctcaagtt gcaacaattt ctgctaataa tgatgcagaa atcgggaatc tgattgctga 900 agcaatggag aaagttggta aaaacggctc tatcactgtt gaagaagcaa aaggatttga 960 aaccgttttg gatgttgttg aaggaatgaa tttcaataga ggttacctct ctagctactt 1020 cgcaacaaat ccagaaactc aagaatgtgt attagaagac gctttggttc taatctacga 1080 taagaaaatt tctgggatca aagatttcct tcctgtttta caacaagttg ctgaatccgg 1140 ccgtcctctt cttattatag cagaagacat tgaaggcgaa gctttagcta ctttggtcgt 1200 gaacagaatt cgtggaggat tccgggtttg cgcagttaaa gctccaggct ttggagatag 1260 aagaaaagct atgttggaag acatcgctat cttaactggc ggtcaactca ttagcgaaga 1320 gttgggcatg aaattagaaa acgctaactt agctatgtta ggtaaagcta aaaaagttat 1380 cgtttctaag gaagacacga ccatcgtcga aggaatgggt gaaaaagaag ctttagaagc 1440 tcgttgcgaa agcatcaaaa aacaaattga agacagctct tctgattacg ataaagaaaa 1500 actccaagag cgtcttgcta agctctctgg tggagtagca gtcattcgcg ttggagctgc 1560 aacagagatt gagatgaaag agaaaaaaga tcgtgtagac gatgctcaac atgctacaat 1620 cgctgctgtt gaagaaggaa ttcttcctgg tggaggaaca gcattaatcc gttgtatccc 1680 tactcttgag gccttcttgc caatgttgac taatgaagat gagcaaattg gagctc 1736 20 1135 DNA Chlamydia trachomatis serovar E 20 ggctcttgat gaaaaagagc ggcaggttat ggctctttat tactatgatg acttggtatt 60 aaaagaaatt gggaagattt taggagtgag cgagtcccga gtttctcaga tacactccaa 120 agctttattg aagttacgag gtacattgtc cagtctgctt tagtaactgt ctccagaaga 180 tcctctttgt atttttccta tcaatattct attggagaag cgcgtcgttt ttttgacgag 240 gtgtctgcta tcgcttgcct tgctataaaa agaacaggat agataagatg ttgctagata 300 agtttatatg gatagatttt tatgcaacag ttaatcgata accttaagaa acggggtatt 360 ctagataatt cttctgcagg attagaaact cgtgccgaag tttgtggaga agagaaagaa 420 atctctctag cagactttcg tggtaagtat gtagtgctct tcttttatcc taaagatttc 480 acctatgtgt gtcctacaga attgcatgct tttcaagata gattggtaga ttttgaagag 540 cggggtgcag tcgtgcttgg ttgctccgtt gacgacattg agacacattc tcgttggctc 600 gctgtagcga gaaatgcagg aggaatagag ggaacagaat atcctctgtt agcagaccct 660 tcttttaaaa tatcagaagc ttttggtgtt ttgaatcctg aaggatcgct cgctttaaga 720 gcgactttcc ttatcgataa acatggggtt gttcgtcatg cggttatcaa tgatcttcct 780 ttagggcgtt ccattgacga ggaattgcgt attttagatt cattgatctt ctttgagaac 840 cacggaatgg tttgtccagc taactggcgt tctggagagc gtggaatggt gccttctgaa 900 gagggattaa aagaatattt ccagacgatg gattaagcat ctttgaaagt aagaaagtcg 960 tacagatctt gatctgaaaa gagaagaagg ctttttaatt ttctgcagag agccagcgag 1020 gcttcaataa tgttgaagtc tccgccacca ggcaatgcta aggcgatgat attagttagt 1080 gaaatctgag tgttaaggaa ataaaggcca aagaagtagc tatcaataaa gaagc 1135 21 731 DNA Chlamydia trachomatis serovar E 21 ttgaagacac tctttctccc ggagtcacag ttcttgaagc tgcaggagct caaatttctt 60 gtaataaagt agtttggact gtgaaagaac tgaatcctgg agagtctcta cagtataaag 120 ttctagtaag agcacaaact cctggacaat tcacaaataa tgttgttgtg aagagctgct 180 ctgactgtgg tacttgtact tcttgcgcag aagcgacaac ttactggaaa ggagttgctg 240 ctactcatat gtgcgtagta gatacttgtg accctgtttg tgtaggagaa aatactgttt 300 accgtatttg tgtcaccaac agaggttctg cagaagatac aaatgtttct ttaatgctta 360 aattctctaa agaactgcaa cctgtatcct tctctggacc aactaaagga acgattacag 420 gcaatacagt agtattcgat tcgttaccta gattaggttc taaagaaact gtagagtttt 480 ctgtaacatt gaaagcagtt acagctggag atgctcgtgg ggaagcgatt ctttcttccg 540 atacattgac tgttccagtt tctgatacag agaatacaca catctattaa tctttgattt 600 tatcgatgtg taggtgccgt ccagggattc ctgggcggct tttttttgtt atctatatga 660 aaataaaaga gttcattttc ggtctcagag catattctag acgggttttt gaaaaaaata 720 agtgtttgtg t 731 22 1181 DNA Chlamydia trachomatis serovar E 22 ctatcgtctg aatgctgaac tgaaacatct ttttgattta gacgcgttag ccgatgctat 60 ggatctatct cgagatctac agttttctta catgggtatt caaaatctgt atgatcgtta 120 ttttaatcac cacgaagatt gccgtttaga aactccccaa attttttgga tgcgcgttgc 180 tatggggttg gcattgaatg agcaagacaa gacttcttgg gctattactt tttataattt 240 gctttcgaca ttccgatata caccagctac gccaaccttg ttcaattcag gtatgcggca 300 ttctcagtta agctcttgct atctttccac tgtacaagat aatttggtca atatctataa 360 ggtcattgct gataacgcta tgctatctaa gtgggcagga gggataggta atgattggac 420 ggcggttcgt gcaacagggg ctttaattaa aggaaccaat ggaagaagtc agggagtaat 480 tccttttatt aaggtgacaa atgatacagc agtcgcagtg aatcaaggtg gtaaacgcaa 540 gggagctgta tgcgtctatt tagaagtttg gcacctcgac tacgaagatt tccttgaatt 600 gagaaagaat acaggggatg agcgtcgacg ggctcatgat gtcaatatag ctagctggat 660 tccagatctt ttcttcaaac gtttacagca aaaagggaca tggactctat tcagcccaga 720 tgatgttccg ggattacacg atgcttatgg ggaagaattt gagcgtttgt acgaagaata 780 tgagcggaag gttgataccg gagagattcg gttattcaag aaggtagaag ctgaagatct 840 gtggagaaaa atgctcagca tgctttttga aacgggacac ccatggatga cttttaaaga 900 tccatccaac atccgttcgg ctcaagatca taaaggcgtg gtgcgttgtt ccaatctgtg 960 tacggagatt ttgttaaact gctcggagac agaaactgct gtttgtaatt taggatcgat 1020 taacttagtt caacatatcg taggggatgg gttagatgag gaaaaactct ctgagacgat 1080 ctctatagca gtccgtatgt tggataacgt gattgatatt aacttttatc caacaaagga 1140 agctaaagag gcgaactttg ctcaccgcgc tattggatta g 1181 23 167 DNA Chlamydia trachomatis serovar E 23 ttaaaaagat tttaaactaa aaagaagatt tttaattata gtttttcaaa atcattttga 60 tatttttaat gctgagataa acaagaaaag cggaaactcc ttgcgacaaa gattttctgc 120 tcgagccctc ttccctgagg attttttagg ggagatccat tcttcca 167 24 1265 DNA Chlamydia trachomatis serovar E 24 caggttcttt ctagacgaac aaagaataat cctatgttga taggggagcc cggagttggg 60 aaaacagcaa tcgctgaagg acttgctctt cgcatagtgc aaggggatgt tccagagagt 120 ttaaaggaaa agcatctgta tgtactggat atgggagctt tgattgcagg tgccaagtat 180 cgaggagagt ttgaagagcg gttaaaaagt gtattgaagg gtgtagaagc ttctgaaggc 240 gagtgtatcc tattcattga tgaagtgcat actttagtag gagcgggagc tacagatgga 300 gctatggatg cagcgaatct attaaagcct gctttagcac gaggcacttt gcattgtatt 360 ggcgctacga ctttgaatga ataccaaaaa tatatagaga aagacgcggc tttggaacgg 420 cgtttccagc ctatttttgt aacagaacct tctttggaag atgctgtatt cattctccgg 480 gggttaaggg aaaaatatga aatttttcat ggtgtgcgca ttacagaagg ggctttgaat 540 gcagctgtag ttctttctta tcgttacatc acagaccgat ttcttcctga taaggcgatt 600 gacctaattg atgaggctgc gagtttaatc cgtatgcaaa taggaagttt acctctgcct 660 attgatgaaa aggaaagaga attatcagct ttaatcgtga aacaagaagc tattaaacgc 720 gagcaagcac cagcttatca ggaagaggct gaagacatgc aaaaagcaat tgaccgggtt 780 aaggaagagc tggccgcttt acgcttgcgc tgggatgaag aaaaaggatt aattgcagga 840 ttaaaagaaa agaagaatgc tttagaaaat ttaaaatttg ccgaagagga agctgagcgt 900 actgccgatt acaatcgggt agcagaacta cgctatagtt tgattccttc tttggaggaa 960 gaaattcatt tagctgagga agctttaaat caaagagatg ggcgcctgct tcaagaggaa 1020 gttgatgagc ggttgattgc gcaagttgtt gcgaattgga ctggaatccc tgtgcaaaaa 1080 atgttggagg gagaatctga aaagttattg gtgttgagga gtctttagaa gaaagggttg 1140 tcggacagcc tttcgctatt gccgcagtca gtgattcgat tcgagctgct cgagtaggat 1200 tgagtgatcc gcagcgtctc cctcacaagg gaatattagc tggcgcggcg aaccgctggc 1260 gaaac 1265 25 463 DNA Chlamydia trachomatis serovar E 25 atgacgaaca accccatgtt tatcgataag gaaagtcgct cttaaagcga gcgatccttc 60 aggattcaaa acaccaaaag cttctgatat tttaaaagaa gggtctgcta acagaggata 120 ttctgttccc tctattcctc ctgcatttct cgctacagcg agccaacgag aatgtgtctc 180 aatgtcgtca acggagcaac caagcacgac tgcaccccgc tcttcaaaat ctaccaatct 240 atcttgaaaa gcatgcaatt ctgtaggaca cacataggtg aaatctttag gataaaagaa 300 gagcactaca tacttaccac gaaagtctgc tagagagatt tctttctctt ctccacaaac 360 aacggcttta ccagaaaaat ccggagcctg tcttccaatt agtgatccca taatactcct 420 cctagaaaga aacaacgcac cagagaggat ttgaacctct gac 463 26 636 DNA Chlamydia trachomatis serovar E 26 ggtagaaaat tctctgaagt cgaatctgaa attaaaacag tcccctacaa agttgctcct 60 aactcgaaag gagatgcggt ctttgatgtg gaacaaaaac tgtacactcc agaagaaatc 120 ggcgctcaga tcctcatgaa gatgaaggaa actgctgagg cttatctcgg agaaacagta 180 acggaagcag tcattaccgt accagcttac tttaacgatt ctcaaagagc ttctacaaaa 240 gatgctggac gtatcgcagg attagatgtt aaacgcatta ttcctgaacc aacagcggcc 300 gctcttgctt atggtattga taaggaagga gataaaaaaa tcgccgtctt cgacttagga 360 ggaggaactt tcgatatttc tatcttggaa atcggtgacg gagtttttga agttctctca 420 accaacgggg atactcactt gggaggagac gacttcgacg gagtcatcat caactggatg 480 cttgatgaat tcaaaaaaca agaaggcatt gatctaagca aagataacat ggctttgcaa 540 agattgaaag atgctgctga aaaagcaaaa atagaattgt ctggtgtatc gtctactgaa 600 atcaatcagc cattcatcac tatcgacgct aatgga 636 27 1797 DNA Chlamydia trachomatis serE 27 atgcatcacc atcaccatca catgagcatc aggggagtag gaggcaacgg gaatagtcga 60 atcccttctc ataatgggga tggatcgaat cgcagaagtc aaaatacgaa gggtaataat 120 aaagttgaag atcgagtttg ttctctatat tcatctcgta gtaacgaaaa tagagaatct 180 ccttatgcag tagtagacgt cagctctatg atcgagagca ccccaacgag tggagagacg 240 acaagagctt cgcgtggagt gctcagtcgt ttccaaagag gtttagtacg aatagctgac 300 aaagtaagac gagctgttca gtgtgcgtgg agttcagtct ctacaagcag atcgtctgca 360 acaagagccg cagaatccgg atcaagtagt cgtactgctc gtggtgcaag ttctgggtat 420 agggagtatt ctccttcagc agctagaggg ctgcgtctta tgttcacaga tttctggaga 480 actcgggttt tacgccagac ctctcctatg gctggagttt ttgggaatct tgatgtgaac 540 gaggctcgtt tgatggctgc gtacacaagt gagtgcgcgg atcatttaga agcgaaggag 600 ttggctggcc ctgacggggt agcggccgcc cgggaaattg ctaaaagatg ggagaaaaga 660 gttagagatc tacaagataa aggtgctgca cgaaaattat taaatgatcc tttaggccga 720 cgaacaccta attatcagag caaaaatcca ggtgagtata ctgtagggaa ttccatgttt 780 tacgatggtc ctcaggtagc gaatctccag aacgtcgaca ctggtttttg gctggacatg 840 agcaatctct cagacgttgt attatccaga gagattcaaa caggacttcg agcacgagct 900 actttggaag aatccatgcc gatgttagag aatttagaag agcgttttag acgtttgcaa 960 gaaacttgtg atgcggctcg tactgagata gaagaatcgg gatggactcg agagtccgca 1020 tcaagaatgg aaggcgatga ggcgcaagga ccttctagag tacaacaagc ttttcagagc 1080 tttgtaaatg aatgtaacag catcgagttc tcatttggga gctttggaga gcatgtgcga 1140 gttctctgcg ctagagtatc acgaggatta gctgccgcag gagaggcgat tcgccgttgc 1200 ttctcttgtt gtaaaggatc gacgcatcgc tacgctcctc gcgatgacct atctcctgaa 1260 ggtgcatcgt tagcagagac tttggctaga ttcgcagatg atatgggaat agagcgaggt 1320 gctgatggaa cctacgatat tcctttggta gatgattgga gaagaggggt tcctagtatt 1380 gaaggagaag gatctgactc gatctatgaa atcatgatgc ctatctatga agttatgaat 1440 atggatctag aaacacgaag atcttttgcg gtacagcaag ggcactatca ggacccaaga 1500 gcttcagatt atgacctccc acgtgctagc gactatgatt tgcctagaag cccatatcct 1560 actccacctt tgcctcctag atatcagcta cagaatatgg atgtagaagc agggttccgt 1620 gaggcagttt atgcttcttt tgtagcagga atgtacaatt atgtagtgac acagccgcaa 1680 gagcgtattc ccaatagtca gcaggtggaa gggattctgc gtgatatgct taccaacggg 1740 tcacagacat ttagagacct gatgaagcgt tggaatagag aagtcgatag ggaataa 1797 28 1983 DNA Chlamydia trachomatis serE 28 atgcatcacc atcaccatca catggaatca ggaccagaat cagtttcttc taatcagagc 60 tcgatgaatc caattattaa tgggcaaatc gcttctaatt cggagaccaa agagtccacg 120 aaggcgtccg aagcgagtcc ttcagcatcg tcctctgtaa gcagctggag ttttttatcc 180 tcagcaaaga atgcattaat ctctcttcgt gatgccatct tgaataaaaa ttccagtcca 240 acagactctc tctctcaatt agaggcctct acttctacct ctacggttac acgtgtagcg 300 gcaaaagatt atgatgaggc taaatcgaat tttgatacgg cgaaaagtgg attagagaac 360 gctaagacac ttgctgaata cgaaacgaaa atggctgatt tgatggcagc tctccaagat 420 atggagcgtt tagctaattc agatcctagt aacaatcata ccgaagaagt aaataatatt 480 aagaaagcgc tcgaagcaca aaaagatact attgataagc tgaataaact cgttacgctg 540 caaaatcaga ataaatcttt aacagaagtg ttgaaaacaa ctgactctgc agatcagatt 600 ccagcgatta atagtcagtt agagatcaac aaaaattctg cagatcaaat tatcaaagat 660 ctggaaagac aaaacataag ttatgaagct gttctcacta acgcaggaga ggttatcaaa 720 gcttcttctg aagcgggaat taagttagga caagctttgc agtctattgt ggatgctggg 780 gaccaaagtc aggctgcagt tctgcaagca cagcaaaata atagcccaga taatattgca 840 gccacgaagg aattaattga tgctgctgaa acgaaggtaa acgagttaaa acaagagcat 900 acagggctaa cggactcgcc tttagtgaaa aaagctgagg agcagattag tcaagcacaa 960 aaagatattc aagagatcaa acctagtggt tcggatattc ctatcgttgg tccgagtggg 1020 tcagctgctt ccgcaggaag tgcggcagga gcgttgaaat cctctaacaa ttcaggaaga 1080 atttccttgt tgcttgatga tgtagacaat gaaatggcag cgattgcact gcaaggtttt 1140 cgatctatga tcgaacaatt taatgtaaac aatcctgcaa cagctaaaga gctacaagct 1200 atggaggctc agctgactgc gatgtcagat caactggttg gtgcggatgg cgagctccca 1260 gccgaaatac aagcaatcaa agatgctctt gcgcaagctt tgaaacaacc atcagcagat 1320 ggtttggcta cagctatggg acaagtggct tttgcagctg ccaaggttgg aggaggctcc 1380 gcaggaacag ctggcactgt ccagatgaat gtaaaacagc tttacaagac agcgttttct 1440 tcgacttctt ccagctctta tgcagcagca ctttccgatg gatattctgc ttacaaaaca 1500 ctgaactctt tatattccga aagcagaagc ggcgtgcagt cagctattag tcaaactgca 1560 aatcccgcgc tttccagaag cgtttctcgt tctggcatag aaagtcaagg acgcagtgca 1620 gatgctagcc aaagagcagc agaaactatt gtcagagata gccaaacgtt aggtgatgta 1680 tatagccgct tacaggttct ggattctttg atgtctacga ttgtgagcaa tccgcaagca 1740 aatcaagaag agattatgca gaagctcacg gcatctatta gcaaagctcc acaatttggg 1800 tatcctgctg ttcagaattc tgcggatagc ttgcagaagt ttgctgcgca attggaaaga 1860 gagtttgttg atggggaacg tagtctcgca gaatctcaag agaatgcgtt tagaaaacag 1920 cccgctttca ttcaacaggt gttggtaaac attgcttctc tattctctgg ttatctttct 1980 taa 1983 29 1224 DNA Chlamydia trachomatis serE 29 gtaacttttc aacatttttc acaatgacaa gaataaaagc aaaaagaaag gctgccgata 60 aaataaaagt tttactgcga gaacagaaga ctaaaactat ctggacgaat aagccggatg 120 cgcaggataa ttgcgcataa aacactttaa tagagagtga tcttatgtct aaaacaccat 180 tatccatagc tcatccttgg catgggccag tattaacacg cgatgattat gaatctcttt 240 gttgctatat agaaatcact ccagccgact ccgttaaatt cgaactggat aaagaaactg 300 gtatcctaaa agtggatcgg ccacaaaagt tttctaactt ttgtccttgc ttatacgggc 360 tgttacctaa gacttattgt ggagatcttt ctggagaata cagtggtcaa caaagtaaca 420 gagagaatat caaaggcgat ggcgatcctc ttgatatctg tgtgttaacg gaaaaaaata 480 ttacacaagg gaacatcctc ttgcaagcgc gtcctatcgg agggattcgt attttagact 540 cggaagaagc cgatgataaa atcatcgctg ttctagaaga tgatttagtc tatggcaata 600 tagaagatat ttctgaatgc ccaggcacag ttttggacat gatccaacac tatttcttaa 660 cctataaagc tactccagaa agcttaattc aagcaaaacc agctaaaatt gaaattgtag 720 gtttatacgg caaaaaagaa gctcaaaaag tcattcgtct tgctcacgaa gactattgca 780 atctttttat gtaaatcgac agaaaaagaa aaggctgttg tgggagattc cacaacggcc 840 cctcctaacc aagttttttt catcctaggg gactttatga agcaaataga taactttgaa 900 caaattcatc tctcgtgccg aattcggcac gagattaaaa caaagctctc aaaaagagtt 960 ggtatcccga attcattcag cagttcccgg tgccaaagtt aaagagatac gctttttatt 1020 aggatagtta tggacgcaca agaaaagaaa tacgacgcat cagccatcac cgttttagaa 1080 ggattgcaag ctgttcgtga gcgtcctgga atgtacattg gtgatacagg agttaccgga 1140 ttgcatcact tggtttatga agtggtggat aacagtatcg atgaggcaat ggcgggtttt 1200 tgtaccgagg tcgttgttcg cata 1224 30 883 DNA Chlamydia trachomatis serE 30 atgttgacta acatggcgac catcagaaac tctgtgaaga cattgaacag aattgaattg 60 gatcttgaag cttctaattc tggtcttacg aaaaaagaga tcgctttatt aacgaaaaga 120 catcgcaagt tgcttaacaa cctggaaggt gttcgtcata tgaactctct cccagggctt 180 ttaattgtaa ttgacccggg ctatgagcgc attgctgtcg cagaagctgg aaaactaggc 240 attcctgtaa tggccttagt tgatacaaac tgcgatccaa caccaatcaa ccacgttatt 300 ccttgcaacg atgattccat taagagtatc cgtctggttg tcaatgtact taaagacgct 360 gttattgatg cgaagaagcg ttcaggcatc gaaattttat ctccagtacg tcctgtagaa 420 agacctgcag aagaagctgt ggaagagttg cctcttccaa caggtgaagc tcaagatgaa 480 gcttcttcta aagaaggttt tttactttgg gcagatattg acaattgcgg ggcattgaaa 540 tgagcgactt ctccatggaa acattgaaaa atttaagaca gcagacaggt gtaggcctga 600 ctaaatgtaa agaggctcta gagcatgcta agggcaattt agaagatgct gttgtttatt 660 tacgtaagct tggtcttgcc tctgcaggca aaaaagaaca ccgagaaaca aaagaaggcg 720 taattgctgc actcgttgat gaacgtggtg cggcacttgt tgaagtcaac gttgaaactg 780 attttgttgc taacaacagt gttttccgag cattcgttac aggtttgtta tccgatcttc 840 ttgaccacaa gcttagcgat gttgaagctt tagctcgcgt aat 883 31 393 DNA Chlamydia trachomatis serE 31 agttgaaaaa ggctgtttct tgcattcaaa aaactatcga gcaagagaga tctattttgt 60 ttgttggaac aaaaaaacag gcaaaacaga tcattagaga agctgctatc gaatgtggcg 120 aattctttgc ttcagagaga tggttgggtg gcatgttgac taacatggcg accatcagaa 180 actctgtgaa gacattgaac agaattgaat tggatcttga agcttctaat tctggtctta 240 cgaaaaaaga gatcgcttta ttaacgaaaa gacatcgcaa gttgcttaac aacctggaag 300 gtgttcgtca tatgaactct ctcccagggc ttttaattgt aattgacccg ggctatgagc 360 gcattgctgt cgcagaagct ggaaaactag gca 393 32 2577 DNA Chlamydia trachomatis serE 32 attacggagg ccatacggta tcttctcgag gaggatttca agggatatgc gtacgaatag 60 ccgatttatt ccgtaactgt ttctctcgta atagaggcac tactactacg ccatctcgaa 120 ctgttatcac tcaggcagat atttatcatc cgactatttc tggacaagga gctcaaccta 180 ttgtctctac aggagataag aaattagata gcgcaattat tcaagcagat ttgcgtgcgc 240 agaataaaca gactttggct acacatattc aaagtaagct aggttctatg gagggacaat 300 ctcctcaaga ttataaagct ggtgcgtata gtgcgctaag attgatgctg tttactccag 360 gcgaaactac tgtgagtagc gagcgggaac gtcaagcgtg cgttacgggt cgggatctct 420 gggaacaggc tgcaggagat cttgctacca atgggaatac agatgggctt atgttaatgg 480 ctaacctatc tgtgggaggg aagcatgtgc ctgcggggca tttaagagaa tacatggata 540 ctgtaaaggg tacgtttact gatgagaacg aggctacaga tcctacggta gatgccattt 600 tagatttagc agcaaaaatc gatgcgacgg aattctctag tcctggttca gggcaagtca 660 ttcttaatta tataggaaat tatggacaag tcgttttaga aaacgaggag atgaaccttc 720 ttgttttaga agatcaaaat gggcaagatc ctcaacgtgt tcaagataac tcaaaagagt 780 tacaaaaact gttagaaaat gctcgaaaaa cagatcctga gttatatttc caaacactaa 840 ctgtcataac ttcttctgtt ttcttagact aaagagaagg tatacggtgt tcggtccttt 900 caactattaa gaggaagtag tggtgagtag cataagccct atagggggga attctgggcc 960 agagggattt tctagtgcat ctcgaggcga tgagattgat gatgtaccag atagtgaaga 1020 gggagagcta gaagagcgcg tttcggatca tgcagagtct atcattaccg agagctcgga 1080 aacgctgttt cgtactactt cttcatcagg ggtcagtgaa gatcttcagc aacacgttag 1140 cttggaggaa tctccacgac aacgaggttt ccttggacgg atccgtgatg cagtagcttc 1200 tatttggaag cgtcgtgttg cacgaaggaa tgaaaactat gatgtgaaaa aagcagaaga 1260 gcagcaaggg attgtgcaat atctgcagga ttcgaaaatg cctgctttaa cgcgtgccta 1320 tcgccatctc cgtgctttca attctgcatg cttacgtacg attcgtgagt ttttcgctac 1380 catttttcgt gctttaaggg atgcgtatta tcgacattgt acacgttctg ggatcaactt 1440 ttgtggagct gataaagact ctttagaagt tcttgttgcg gtgggtttgc ttttgcgtat 1500 ggctacctta cgctcttttg aacatgtcgg tgggaattac gaagatcgat tagtaaataa 1560 tgatgctccg gtgacaggtg cggggagaac tcttgttgat gatgctgtag acgatattga 1620 atcgatttta aatacgagaa ccaactggcc tcaacatgtc atgatagggt tttctcgtgg 1680 tctcgttcaa ttatgtgcga ctccttataa tgcgacttct caagaatgtt tcaagtcgat 1740 tgttcgttta gaaaaagaag acccttcttc agattattct caagctttat tattagcagg 1800 gataatagat cgcttggcgg agaaagcccc tatggctgca aagtatgttt tggatgcatt 1860 gcgtgttcga acttcggagc tcataggaga actcattatt ctcgatttgc ttcctcctgt 1920 atggaaggtt ggccgcggag gcgtattccc tcctgtgaat gagcagctcg ttgtgcaaat 1980 tgttaatgca aacgtagaac gattgcattc cactttcgct catgagccac aagcttattt 2040 gcgtatgatc gaaggtttgg taaccaattt ctttttctta cctagcgagg aagatccttc 2100 ttcggttggg aatatctaag aacattttct aatagggaag aggataaata gcgtgaaata 2160 atactgatta tgtgaagaat aggcaaaaag acctaaatcc ttatatgcta ttagattctc 2220 gtttccctac agattattat ttacgtatcc tagaattagt catccgggat gcttcttgta 2280 aattggtata taaccgacgc ctgcatatgt tggaggcgat ccctcttgat caaaaacttt 2340 ctactgatca agagggggaa tcaagtattt tacgagaagt gattagcgag ctacttgcgc 2400 attctgggga aagttatgcg atttcagctc aattacttgc cgtaatcgat atttatttaa 2460 aacaagagca accgtcgaat tcatggttcg ctcgaatctt tcggaagaga gagcgggcta 2520 gaaaacgaca aacaattaat aagttgcttt tgttaaaaag tatcctattt tttgaac 2577 33 554 DNA Chlamydia trachomatis serE 33 ttctttatta aaaaaaactt tctcttttct ctcagacttc ttatgagtca agaaactcaa 60 cgagtcttgg tgtatggaga aggatttttt agaaaatgtt tatcgtcatt tccgttaccg 120 tttttttaaa ttaagtgtac ttccagctct tctcggactc tggctatttt ttactcctaa 180 tattcttaac tatttggatt cttctgttat tttatcagat aaaatttgcg gcgtcctttt 240 aattttatta tcagctttat ccttttataa tcctgttatt ttgcaactag gcatttttat 300 tgggctctgg gtttctttct tttcttgttc ttccgaccta cttcctttag tatttgctca 360 tgattcgcta ctaggttttg ccacactagc tattattttt ctactcccta atcgtcctga 420 agatctagaa gttggtccta ctattccaga aacttgccat tataatcctt cttccggagg 480 gaaaagagct gcggttctta tttttgcttt tgtaggatgg ttacaaagtc gctacttaac 540 ttccgcggca cgag 554 34 1433 DNA Chlamydia trachomatis serE 34 ctgcacgaaa attattaaat gatcctttag gccgacgaac acctaattat cagagcaaaa 60 atccaggtga gtatactgta gggaattcca tgttttacga tggtcctcag gtagcgaatc 120 tccagaacgt cgacactggt ttttggctgg acatgagcaa tctctcagac gttgtattat 180 ccagagagat tcaaacagga cttcgagcac gagctacttt ggaagaatcc atgccgatgt 240 tagagaattt agaagagcgt tttagacgtt tgcaagaaac ttgtgatgcg gctcgtactg 300 agatagaaga atcgggatgg actcgagagt ccgcatcaag aatggaaggc gatgaggcgc 360 aaggaccttc tagagcacaa caagcttttc agagctttgt aaatgaatgt aacagcatcg 420 agttctcatt tgggagcttt ggagagcatg tgcgagttct ctgcgctaga gtatcacgag 480 gattagctgc cgcaggagag gcgattcgcc gttgcttctc ttgttgtaaa ggatcgacgc 540 atcgctacgc tcctcgcgat gacctatctc ctgaaggtgc atcgttagca gagactttgg 600 ctagattcgc agatgatatg ggaatagagc gaggtgctga tggaacctac gatattcctt 660 tggtagatga ttggagaaga ggggttccta gtattgaagg agaaggatct gactcgatct 720 atgaaatcat gatgcctatc tatgaagtta tgaatatgga tctagaaaca cgaagatctt 780 ttgcggtaca gcaagggcac tatcaggacc caagagcttc agattatgac ctcccacgtg 840 ctagcgacta tgatttgcct agaagcccat atcctactcc acctttgcct cctagatatc 900 agctacagaa tatggatgta gaagcagggt tccgtgaggc agtttatgct tcttttgtag 960 caggaatgta caattatgta gtgacacagc cgcaagagcg tattcccaat agtcagcagg 1020 tggaagggat tctgcgtgat atgcttacca acgggtcaca gacatttaga gacctgatga 1080 agcgttggaa tagagaagtc gatagggaat aaactggtat ctaccatagg tttgtagcaa 1140 aaaactaagc ccaccaagaa gaaattctct ttggtgggct tcttttttta ttcaaaaaag 1200 aaagccctct tcaagattat accaagatgg gatgtataat ctgaaaggaa ggcgttttat 1260 tctctatcca tatgatggtg gtggtatcct cctttagagg agcagcagtc tccatgacgt 1320 tttttgaagc agcacttcaa gaagtttagg cagaccataa ccccagcgat tcccgttact 1380 acataagctg cttgtgtcca catggttcct tcaccaagca ggtgagtaag tag 1433 35 196 DNA Chlamydia trachomatis 35 ctcgtgccga tgatacagca gtcgcagtga atcaaggtgg taaacgcaag ggagctgtat 60 gcgtctattt agaagtttgg cacctcgact acgaagattt ccttgaattg agaaagaata 120 caggggatga gcgtcgacgg gctcatgatg tcaatatagc tagctggatt ccagatcttt 180 tcttcaaacg tttaca 196 36 1990 DNA Chlamydia trachomatis 36 ttcactaggc tcatgagcct ctaactcttc tggagtaact cctagagcaa acacaaactg 60 cttccacaaa tcaatatgat tagggtaacc gttctcttca tccatcaagt tatctaacaa 120 taacttacgc gcctctaaat catcgcaacg actatgaatc gcagataaat atttaggaaa 180 ggctttgata tgtaaataat agtctttggc atacgcctgt aattgctctt tagtaagctc 240 ccccttcgac catttcacat aaaacgtgtg ttctagcata tgcttatttt gaataattaa 300 atctaactga tctaaaaaat tcataaacac ctccatcatt tcttttcttg actccacgta 360 accgcttgca aaaaaggtcc gtataagtcc tctgtttcat ctatgcgcaa agaacaatac 420 tcttctcgag aagtaggatg tgaatggtag accatattag gtgcctgctc tatcaccgct 480 aacggtgttt gctcattccc ctctcccata caaacaacag ccgcaactgc taaggcatct 540 acaagattac tttgcgtcat ctgtaagaga cgaccgaaac aatctagcga tcctatatag 600 ttgtgtaatg gagaaaatcc ataccaacac agcccgatac ccagtactcc acgccgcatt 660 ggagtagtat ggctatctgt aatgattacg cctagctctt tcactcgaaa ataatttctt 720 aaccattctc cgatgcgatt acacgatccc aaaatatctt taggatataa aacaaaaggc 780 tggtccgtat tcgattcatc aatccctgca gaaggaatca aaataccttc ttttttcgtt 840 agatatatcc cgcttttctc acaaaacaaa taagcatccg cttctttttt tatcagctct 900 gctttgcaca ttcttgcatc agcgacagcg ccttcacata aactcacaat ctttgaagag 960 acaactacca cactccgttc ttgcagaggc ggcaaagcct cttgcaagat ctcttgaagc 1020 gaatcatgtg caaatacttt acgtgttttg atcggagtta ttttcataat aataaatact 1080 gaaatcctct gtattacaaa tacattcctt cttccatcct gataatcgcg tgatagggaa 1140 gaaagtatcg ccccaatatt cctttttgat atgtgtgaca aaacaagctt tcagaaggtt 1200 ttgttggaaa aaactttcaa agagctccgc tcccccaatt aaaaacggat gattcaaaga 1260 tagtgtccca tactctgcaa aggaagaaac tcctatgcat tgtggtggat gcatcctgcg 1320 agaaaagaca acgatatccc gcccatgctt atacttgtct ggaagagact cccaagtctt 1380 tcgtcccata atgatgggat gatttcgaat ggtttctgca aaaaaacgta gatcttcggg 1440 ataactccaa gggagcttgc ctaaagctcc catcactcct ctgggatcaa tagcaacgat 1500 acctgttgct tggatcatac aaacatacca gcccaagcag cagcggctaa ggcacgtctg 1560 ttaccttcaa cctgatgcac gcgtagataa tcaactcctc gatcatgaag agatacagaa 1620 cagccgatcg tttcccaatc acgatcgtta ctattaaatc ggcccaacat actcaaacac 1680 gattttctag aatggcctat taatacagga cactctaaaa cacgtttaaa ctgctttact 1740 ccatccatca ataacatcga ctgaacggga gtcttcccaa atcctattcc tggatcgaaa 1800 acaacttgcc aacttgtatc taaacctact tgagcaaatt gttctaactg ggactctccc 1860 caacgcaaca tttgctcaat aggagattct tcataagaaa gtacacaatc tggtcttgga 1920 ggcagcgaac acgaatgatt tattaatagc cgtagcccaa actccttcgc caaatgagcc 1980 atttccaaag 1990 37 2093 DNA Chlamydia trachomatis 37 cagaaactct atccgcatac cttcttcggc aaattgatac caattttgcc tcttctcagg 60 aacgtactat agctcagtat attgtaggca acctctcccc agaaggactc tttttagaaa 120 atcctagtct tgtggctgca gatttaaacg tttccgaaca ccttttccac aaggtatggc 180 aacgtatcca acaattacat cctttaggag tcggagcgcc ttccctacag tcctactggg 240 tatcgctact acagacatct ccccataagg aggctttagc tattattcgc aaccatttcc 300 ctagattagc tcgttgtgat ttcactacta tcgctaggaa aatgcatgca accacaacag 360 agattcttac atttcttaga cacgcttttg cttccatccc ttggtgtcca gcagcaggct 420 tttccgagac actgcacccc cctgctccag cgcttcctga tgcctacctt tccttctcgc 480 gaaactctta ttgggatgtc tctattaata aagattgtct cccctctatt agactcaacg 540 acaccgtact agatatctat ccttctcttc ctcgtgaaga gaaagaccac ctatcgcaac 600 aaatccgagc agcaaaacaa ttgcttcgca atgtaaaaaa acgagaagaa acgttattgg 660 ctatccttcg agttctcatc ccctaccaag aagagttcct tcttaaaaaa cgcacctctc 720 ctaaagcttt ttctgtaaaa caaatagctc gcgaactctc tcttcatgaa gctaccgttt 780 gtcgcgccat tgataataaa acgttagcaa cccctgttgg attactccct atgcgatcgc 840 tatttccaca agcggttgga tcctgccccg atcaatctaa agcaactatt ttgcattgga 900 tccaccagtg gatttctaca gaaaaacatc ctctatctga tgcagctatt agccaaaaaa 960 ttattgagaa gggcatcccc tgcgcacgac gcacagtagc caaatatcgt tcgcaactga 1020 atatcccacc tgcgcaccaa cgcaaacacc tatgctctgt tttaacaaca acacgcacag 1080 agaattctcg acatactatc taatcggata tgtaaagctg ctttacatcc cttgaactag 1140 aaataaaatg gaaataaaaa gcccagaaca agagaagttg ttctgggctg acagaagctg 1200 tcagatcatt ttaataagat tgatgacaac tacgacaagt tcctggatcc aaaaaagaat 1260 ctaaaaagcc atacaaagat tgcgttactt cttgcgatgc ctctaacact ttatcagcgt 1320 catctttgag aagcatctca atgagcgctt tttcttctct agcatgccgc acatccgctt 1380 cttcatgttc tgtgaaatat gcatagtctt caggattgga aaatccaaag tactcagtca 1440 atccacgaat tttctctcta gcgatacgtg gaatttgact ctcataagaa tacaaagcag 1500 ccactcctgc agctaaagaa tctcctgtac accaccgcac gaaagtagct actttcgctt 1560 ttgctgcttc actaggctca tgagcctcta actcttctgg agtaactcct agagcaaaca 1620 caaactgctt ccacaaatca atatgattag ggtaaccgtt ctcttcatcc atcaagttat 1680 ctaacaataa cttacgcgcc tctaaatcat cgcaacgact atgaatcgca gataaatatt 1740 taggaaaggc tttgatatgt aaataatagt ctttggcata cgcctgtaat tgctctttag 1800 taagctcccc cttcgaccat ttcacataaa acgtgtgttc tagcatatgc ttattttgaa 1860 taattaaatc taactgatct aaaaaattca taaacacctc catcatttct tttcttgact 1920 ccacgtaacc gcttgcaaaa aaggtccgta taagtcctct gtttcatcta tgcgcaaaga 1980 acaatactct tctcgagaag taggatgtga atggtagacc atattaggtg cctgctctat 2040 caccgctaac ggtgtttgct cattcccctc tcccatacaa acaacagccg caa 2093 38 1834 DNA Chlamydia trachomatis 38 ctctacttct acctctacgg ttacacgtgt agcggcaaaa gattatgatg aggctaaatc 60 gaattttgat acggcgaaaa gtggattaga gaacgctaag acacttgctg aatacgaaac 120 gaaaatggct gatttgatgg cagctctcca agatatggag cgtttagcta attcagatcc 180 tagtaacaat cataccgaag aagtaaataa tattaagaaa gcgctcgaag cacaaaaaga 240 tactattgat aagctgaata aactcgttac gctgcaaaat cagaataaat ctttaacaga 300 agtgttgaaa acaactgact ctgcagatca gattccagcg attaatagtc agttagagat 360 caacaaaaat tctgcagatc aaattatcaa agatctggaa agacaaaaca taagttatga 420 agctgttctc actaacgcag gagaggttat caaagcttct tctgaagcgg gaattaagtt 480 aggacaagct ttgcagtcta ttgtggatgc tggggaccaa agtcaggctg cagttctgca 540 agcacagcaa aataatagcc cagataatat tgcagccacg aaggaattaa ttgatgctgc 600 tgaaacgaag gtaaacgagt taaaacaaga gcatacaggg ctaacggact cgcctttagt 660 gaaaaaagct gaggagcaga ttagtcaagc acaaaaagat attcaagaga tcaaacctag 720 tggttcggat attcctatcg ttggtccgag tgggtcagct gcttccgcag gaagtgcggc 780 aggagcgttg aaatcctcta acaattcagg aagaatttcc ttgttgcttg atgatgtaga 840 caatgaaatg gcagcgattg cactgcaagg ttttcgatct atgatcgaac aatttaatgt 900 aaacaatcct gcaacagcta aagagctaca agctatggag gctcagctga ctgcgatgtc 960 agatcaactg gttggtgcgg atggcgagct cccagccgaa atacaagcaa tcaaagatgc 1020 tcttgcgcaa gctttgaaac aaccatcagc agatggtttg gctacagcta tgggacaagt 1080 ggcttttgca gctgccaagg ttggaggagg ctccgcagga acagctggca ctgtccagat 1140 gaatgtaaaa cagctttaca agacagcgtt ttcttcgact tcttccagct cttatgcagc 1200 agcactttcc gatggatatt ctgcttacaa aacactgaac tctttatatt ccgaaagcag 1260 aagcggcgtg cagtcagcta ttagtcaaac tgcaaatccc gcgctttcca gaagcgtttc 1320 tcgttctggc atagaaagtc aaggacgcag tgcagatgct agccaaagag cagcagaaac 1380 tattgtcaga gatagccaaa cgttaggtga tgtatatagc cgcttacagg ttctggattc 1440 tttgatgtct acgattgtga gcaatccgca agcaaatcaa gaagagatta tgcagaagct 1500 cacggcatct attagcaaag ctccacaatt tgggtatcct gctgttcaga attctgcgga 1560 tagcttgcag aagtttgctg cgcaattgga aagagagttt gttgatgggg aacgtagtct 1620 cgcagaatct caagagaatg cgtttagaaa acagcccgct ttcattcaac aggtgttggt 1680 aaacattgct tctctattct ctggttatct ttcttaacgt gtgattgaag tttgtgaatg 1740 agggggagcc aaaaaagaat ttcttttttg gctctttttt cttttcaaag gaatctcgtg 1800 tctacagaag tcttttcagc acgagcggca cgag 1834 39 1180 DNA Chlamydia trachomatis 39 agaaatttct caaaaatcaa agttttttac atttaagggg catcttacca ccacaacaac 60 cttctatgag cagaaactat ccattaaata aaagtaatta aatataacaa aaacatcttg 120 attatttttg ttaaaagaaa tacttaatga gttttattta attaacgaaa cgaaaagctt 180 gctaatgaaa attattcaca cagctatcga atttgctccg gtaatcaaag ccggaggcct 240 gggagacgcg ctatacggac tagcaaaagc tttagccgct aatcacacaa cggaagtggt 300 aatcccttta taccctaaat tatttacttt gcccaaagaa caagatcttt gctcgatcca 360 aaaattatct tatttttttg ctggagagca agaagcaact gctttctcct acttttatga 420 aggaattaaa gtaactctat tcaaactcga cacacagcca gagttattcg agaatgcgga 480 aacaatctac acaagcgatg atgccttccg tttttgcgct ttttctgctg ctgcggcctc 540 ctacatccaa aaagaaggag ccaatatcgt tcatttacac gattggcata caggattagt 600 tgctggacta ctcaaacaac agccctgctc tcaattacaa aagattgttc ttaccctaca 660 taattttggt tatcgaggct atacaacacg agaaatatta gaagcctcct ctttgaatga 720 attttatatc agccagtacc aactatttcg cgatccacaa acttgtgtgt tgctaaaagg 780 agctttatac tgttcagatt tcgtgactac ggtttctcct acatacgcca aagaaattct 840 tgaagattat tccgattacg aaattcacga tgccattact gctagacaac atcatctccg 900 cgggatttta aatggaatcg acacgacaat ttgggggcct gaaacggatc ccaatttagc 960 gaaaaactac actaaagagc ttttcgagac cccttcaatt ttttttgaag ctaaagccga 1020 gaataaaaaa gccttgtacg aaagattagg cctctcttta gaacactctc cttgcgtgtg 1080 cattatttct agaattgctg agcagaaagg tcctcacttt atgaaacagg ccattctcca 1140 tgcactagaa aacgcttaca cgctcattat tataggtacc 1180 40 1297 DNA Chlamydia trachomatis 40 agaaacttct ataggagggg atgtgatcga cataggtacg tgtgagttat gggatatcga 60 tttgttgtat aatggataag aaattctctg aagataaaga ggctcctcca actaaaagac 120 cattaacatc agggcagagg gcaagtgagc gagcattatc ggctttcaca gatcctccgt 180 aaagaatggg ggtgcgttcc gcaatatctt tggaaaagag agaagcaatc gtttttctac 240 agaaagcatg ggtttcctga actagatcag gatgagctac ttttccggtg cctatagccc 300 agactggttc ataagctaga atgaaagagg cttgctcagg gagtttagat aatcctatag 360 tcagttgatt taaaagaata tcttgagttg ctccagattc ttgttcttct aaagtttctc 420 caatacacag aactggaatc attccactat ggatagctgc agcagctttt tcagcaagta 480 caggattttg ttcatgaaag atatgacgtc tttcggaatg tccgatgaga acaaaatcga 540 ctccgatatc tttgagcatt ggggctgaaa tctcaccagt aaaagctcct gagtcagctt 600 catgagtggt ttgggctcca agaaagatgg gggaatcgct tacagcttgt tgacaagctg 660 acagcagtgt gaaaggagga atgattcctg taatgatttg gggattagac agaatgtcac 720 tagagatgaa actttttaaa aaggtctgag cttcggtaag cgtcttgttc attttccaat 780 taccgaaaac aaattgcttt gatggctcag agtggagaag gtgggcccaa gttggaaatg 840 gttttctgtg agtttctttg tctgtaaaca tgagatttgc tgaataacct gtgcatgtat 900 tttgtttgta agatagatca aagcgtaata ctcgatttct tgcaaggaag gcttattttt 960 atatgattta ttttctattg ctttgatata aatctcttgg atatgctaat cttcctgtct 1020 tacttttttc tgtgaatttg cttaaatagt tggttttagc ccctttgtta tatgaaggtg 1080 aaaatttgtg gtattacgca tcctgatgat gctcgggaag ctgccaaagc gggagccgat 1140 tacattggca tgatttttgc taaagattct cgaagatgtg tgagtgaaga aaaagcaaag 1200 tatatcgtag aggctataca ggaagggaat tcggaacctg ttggagtatt cccagagcat 1260 tcagtagaag aaattttagc tattactgag acgacag 1297 41 1141 DNA Chlamydia trachomatis 41 ctttccataa gttctttctt tcaatgattc tagcttattc ttgctgctct ttaagtgggg 60 gggggtatgc agcagaaatc atgattcctc aaggaattta cgatggggag acgttaactg 120 tatcatttcc ctatactgtt ataggagatc cgagtgggac tactgttttt tctgcaggag 180 agttaacgtt aaaaaatctt gacaattcta ttgcagcttt gcctttaagt tgttttggga 240 acttattagg gagttttact gttttaggga gaggacactc gttgactttc gagaacatac 300 ggacttctac aaatggagct gcactaagtg acagcgctaa tagcgggtta tttactattg 360 agggttttaa agaattatct ttttccaatt gcaactcatt acttgccgta ctgcctgctg 420 caacgactaa taatggtagc cagactccga cgacaacatc tacaccgtct aatggtacta 480 tttattctaa aacagatctt ttgttactca ataatgagaa gttctcattc tatagtaatt 540 tagtctctgg agatggggga gctatagatg ctaagagctt aacggttcaa ggaattagca 600 agctttgtgt cttccaagaa aatactgctc aagctgatgg gggagcttgt caagtagtca 660 ccagtttctc tgctatggct aacgaggctc ctattgcctt tatagcgaat gttgcaggag 720 taagaggggg agggattgct gctgttcagg atgggcagca gggagtgtca tcatctactt 780 caacagaaga tccagtagta agtttttcca gaaatactgc ggtagagttt gatgggaacg 840 tagcccgagt aggaggaggg atttactcct acgggaacgt tgctttcctg aataatggaa 900 aaaccttgtt tctcaacaat gttgcttctc ctgtttacat tgctgctgag caaccaacaa 960 atggacaggc ttctaatacg agtgataatt acggagatgg aggagctatc ttctgtaaga 1020 atggtgcgca agcagcagga tccaataact ctggatcagt ttcctttgat ggagagggag 1080 tagttttctt tagtagcaat gtagctgctg ggaaaggggg agctatttat gccaaaaagc 1140 t 1141 42 822 DNA Chlamydia trachomatis 42 cggcacgagt gtatgctgaa caagcagaag ggcccactga gaacgagcct ctgagaaaaa 60 aagcttttat taaaaaatta aaaaaatact ttacaaaact tattctgtag gttgagaaag 120 agcttcaacg taagcattcc aaagctccgt acttacaata ttattgcgga tagagcgaat 180 taattctctt tttagtgatg gaagaggttt tttggggctg aagcgagcca aaagatcttt 240 atcgccaact tgacgagcta actctaacac ccgttcgata tcggtttttg tgaaattcac 300 aaagtctctg cgctttttag aacctcgagg agctcgtggt ttagggctaa tggatctggg 360 agtgatagaa tcgatcacaa acgtctttaa catttttaac agttgctcag gagcagagtt 420 cttcattttt tttaaagtaa aatgatgcat gtagccgcct gttggccctg ggagataacg 480 acaaagatca ttttctttac ttcctccgac tttgctaatc gctttagtta tgagctgctc 540 tatttcttct tggatagtaa tctgtgccgt agccatgaat agctccttag tgggtagtct 600 agttctacag atggtagttt ttgctttatt aattgtaata gtcaactaag tctgtttttt 660 tcgatttaat gttcagtcga aataaaaatc aattagtgtt tatcttttgg tgaattctat 720 agtggttttt gcttttttcg caatctcatt ttagagattt ttttgatttg gacaaaagaa 780 aataaagtac ttcagattgt tttctaagtt tgtttgcata aa 822 43 1634 DNA Chlamydia trachomatis 43 ataaaaaatt aaattttggc tactccctgc tcctaataga atttcaccag aggagcttgc 60 tactgttatt gcatttcttc taggaggatt agctgacgta ctggtaccat ttgcattagt 120 tacattagtc acaatatttt cattaaaaat aatagcatgg cggtcggcag aaattttgga 180 gttactggtt ccgtctatat agatagcgcc ccccttatta ttggcgatat tgtttataaa 240 gtaggtaggg ccattatcca ctagggtaac tacaggagcg taaatagctc cgccataatt 300 ttttgtgata ttgtcactaa aaaagatcct accacgattg cctgtaacat ctaggcgagt 360 agttacttta attgctcctc catcagaagc ttctgaagaa gctgtttcta catttttaaa 420 gcagcgattg ttatagaaaa cgatgttacc acgatttcct gttagagaac agatagggga 480 gaagatcgct cctcctgcac aacaggcgtt attgatgaag aagagatcgc agttattact 540 ctcaaaagaa ttgctcgttc cagcatagat agcgccacct tttcctgctg tattagtttg 600 aatacagatg ttgtccataa agagaaaaca agactgattc tcgctcacaa caaaggtatt 660 agcggtacta atggctcctc cttggacata agaaaagttc ttcataaatc cgaccacatc 720 atgattatga tttatgtaaa gattttgagc atgaatggct ccgccttctc ttattttatc 780 agcagcataa ggatttctcc atgtaaatag tctgcaacaa gtattatttt caaagattac 840 aggacctatt gtatcacgaa tctccacggt aggagaattg ggactcgcat aaccaatcgc 900 accaccactt tcaggggtga gattttttgc aaaataaata ccttcttttt gtgtatcaaa 960 aaagcttagg taatctgtta ttgtgacagc agctccttca ttgggagttt tttgtagaat 1020 agccagtatg tagcgtaggt tatcgagata gcagttagtg agattgtgag tgtctcctgt 1080 caaactaatt ttatttgata gcgactcttt cgtaggatct ggaactgagt tgggcataag 1140 aaagattcta gaaggaacct ctctagctag tcctgatagg gagtttccga taaggaaaaa 1200 gaaaaacgct tttttcataa ttaaaagacc agagctcctc ctgcattgat gtagtgtgag 1260 acagtggaag tagccacttc tgcttgatag ttagcaaata gtttcagatg agaaaatttg 1320 agggagtgag aacctctccc ataaaaggaa tgtttagcta atggggtatt tgtggtgacc 1380 caagaaccgt tattttggat taatagtgtg ttgagtagag gacgtttcca gtagagggtg 1440 ggttggtaag ctagttccat ttcccaagag agtgttggcc atgtatcaga agaataagct 1500 cctttgattc ctattggaga gacaacggca gtatgggctt gctctaatgt aaataatcta 1560 gctagatcac cgctttctcg gatagaagct ggttctgttc gagagaataa agcctgagca 1620 aatggggtga gcat 1634 44 1862 DNA Chlamydia trachomatis 44 gttagctttc cctccaggga tttgcaattt aatgatttta atgatttttt tattcgacat 60 attcaaccct ttcatttggc aagacatgga gtcatagtta gagggtctat gtatgcttct 120 ctaacaagca atatagaagt atatggccat ggaagatatg agtatcgaga tacttctcga 180 ggttatggtt tgagtgcagg aagtaaagtc cggttctaaa aatattggtt agatagttaa 240 gtgttagcga tgcctttttc tttgagatct acatcatttt gttttttagc ttgtttgtgt 300 tcctattcgt atggattcgc gagctctcct caagtgttaa cacctaatgt aaccactcct 360 tttaaggggg acgatgttta cttgaatgga gactgcgctt ttgtcaatgt ctatgcaggg 420 gcagagaacg gctcaattat ctcagctaat ggcgacaatt taacgattac cggacaaaac 480 catacattat catttacaga ttctcaaggg ccagttcttc aaaattatgc cttcatttca 540 gcaggagaga cacttactct gaaagatttt tcgagtttga tgttctcgaa aaatgtttct 600 tgcggagaaa agggaatgat ctcagggaaa accgtgagta tttccggagc aggcgaagtg 660 attttttggg ataactctgt ggggtattct cctttgtcta ttgtgccagc atcgactcca 720 actcctccag caccagcacc agctcctgct gcttcaagct ctttatctcc aacagttagt 780 gatgctcgga aagggtctat tttttctgta gagactagtt tggagatctc aggcgtcaaa 840 aaaggggtca tgttcgataa taatgccggg aattttggaa cagtttttcg aggtaatagt 900 aataataatg ctggtagtgg gggtagtggg tctgctacaa caccaagttt tacagttaaa 960 aactgtaaag ggaaagtttc tttcacagat aacgtagcct cctgtggagg cggagtagtc 1020 tacaaaggaa ctgtgctttt caaagacaat gaaggaggca tattcttccg agggaacaca 1080 gcatacgatg atttagggat tcttgctgct actagtcggg atcagaatac ggagacagga 1140 ggcggtggag gagttatttg ctctccagat gattctgtaa agtttgaagg caataaaggt 1200 tctattgttt ttgattacaa ctttgcaaaa ggcagaggcg gaagcatcct aacgaaagaa 1260 ttctctcttg tagcagatga ttcggttgtc tttagtaaca atacagcaga aaaaggcggt 1320 ggagctattt atgctcctac tatcgatata agcacgaatg gaggatcgat tctgtttgaa 1380 agaaaccgag ctgcagaagg aggcgccatc tgcgtgagtg aagcaagctc tggttcaact 1440 ggaaatctta ctttaagcgc ttctgatggg gatattgttt tttctgggaa tatgacgagt 1500 gatcgtcctg gagagcgcag cgcagcaaga atcttaagtg atggaacgac tgtttcttta 1560 aatgcttccg gactatcgaa gctgatcttt tatgatcctg tagtacaaaa taattcagca 1620 gcgggtgcat cgacaccatc accatcttct tcttctatgc ctggtgctgt cacgattaat 1680 cagtccggta atggatctgt gatttttacc gccgagtcat tgactccttc agaaaaactt 1740 caagttctta actctacttc taacttccca ggagctctga ctgtgtcagg aggggagttg 1800 gttgtgacgg aaggagctac cttaactact gggaccatta cagccacctc tggctcgtgc 1860 cg 1862 45 1668 DNA Chlamydia trachomatis 45 agaaaatccg atagcagaaa tagaagaatt cgatgtggtt gcgaacaaag ctcaagattg 60 ggatgtcgat gtagctatgt caaattcttt tggttttggc ggacacaatt caacgatatt 120 attttcgagg tatgaacctt cattatgatg aaaactaagc acgaatattc ttttggcgtt 180 attcctatca gattttttgg tactccggat agaagtacct taaaggcttg ttttatctgc 240 catacagatg ggaaacattg gggtttccct aaggggcatg ctgaggaaaa agaaggccct 300 caggaagctg ctgagagaga acttgtagaa gaaactggtt tggggattgt taattttttc 360 ccaaaaatat ttgtggaaaa ttattccttt aatgacaaag aagaaatctt tgtacgtaaa 420 gaggtaactt attttcttgc agaggttaaa ggcgaagtac atgctgatcc tgatgagatc 480 tgtgatgtgc agtggctaag ctttcaagaa ggtttacgcc ttttaaattt cccagaaatt 540 cgtaatattg ttacggaagc agatgaattt gttcaaagtt atctatttgc ttcataaagt 600 cccctaggat gaaaaaaact tggttaggag gggccgttgt ggaatctccc acaacagcct 660 tttctttttc tgtcgattta cataaaaaga ttgcaatagt cttcgtgagc aagacgaatg 720 actttttgag cttctttttt gccgtataaa cctacaattt caattttagc tggttttgct 780 tgaattaagc tttctggagt agctttatag gttaagaaat agtgttggat catgtccaaa 840 actgtgcctg ggcattcaga aatatcttct atattgccat agactaaatc atcttctaga 900 acagcgatga ttttatcatc ggcttcttcc gagtctaaaa tacgaatccc tccgatagga 960 cgcgcttgca agaggatgtt cccttgtgta atattttttt ccgttaacac acagatatca 1020 agaggatcgc catcgccttt gatattctct ctgttacttt gttgaccact gtattctcca 1080 gaaagatctc cacaataagt cttaggtaac agcccgtata agcaaggaca aaagttagaa 1140 aacttttgtg gccgatccac ttttaggata ccagtttctt tatccagttc gaatttaacg 1200 gagtcggctg gagtgatttc tatatagcaa caaagagatt cataatcatc gcgtgttaat 1260 actggcccat gccaaggatg agctatggat aatggtgttt tagacataag atcactctct 1320 attaaagtgt tttatgcgca attatcctgc gcatccggct tattcgtcca gatagtttta 1380 gtcttctgtt ctcgcagtaa aacttttatt ttatcggcag cctttctttt tgcttttatt 1440 cttgtcattg tgaaaaatgt tgaaaagtta ctcgtggcaa cctttcagac aggttttttg 1500 tacgaaagac gagagtgatt gtactgcaaa ataatatgag ccggacgtag gatatgaaat 1560 actctttgca aatagaagac ctacatattg aaggatatga acaggttttg aaagttactt 1620 gcgagtctgt acagttagtt gctgtaattg ctattcatca gacaaaag 1668 46 2010 DNA Chlamydia trachomatis 46 atatcaaagt tgggcaaatg acagagccgc tcaaggacca gcaaataatc cttgggacaa 60 catcaacacc tgtcgcagcc aaaatgacag cttctgatgg aatatcttta acagtctcca 120 ataattcatc aaccaatgct tctattacaa ttggtttgga tgcggaaaaa gcttaccagc 180 ttattctaga aaagttggga gatcaaattc ttgatggaat tgctgatact attgttgata 240 gtacagtcca agatatttta gacaaaatca aaacagaccc ttctctaggt ttgttgaaag 300 cttttaacaa ctttccaatc actaataaaa ttcaatgcaa cgggttattc actcccagta 360 acattgaaac tttattagga ggaactgaaa taggaaaatt cacagtcaca cccaaaagct 420 ctgggagcat gttcttagtc tcagcagata ttattgcatc aagaatggaa ggcggcgttg 480 ttctagcttt ggtacgagaa ggtgattcta agccctgcgc gattagttat ggatactcat 540 caggcattcc taatttatgt agtctaagaa ccagtattac taatacagga ttgactccga 600 caacgtattc attacgtgta ggcggtttag aaagcggtgt ggtatgggtt aatgcccttt 660 ctaatggcaa tgatatttta ggaataacaa atacttctaa tgtatctttt ttagaggtaa 720 tacctcaaac aaacgcttaa acaattttta ttggattttt cttataggtt ttatatttag 780 agaaaacagt tcgaattacg gggtttgtta tgcaaaataa aagaaaagtg agggacgatt 840 ttattaaaat tgttaaagat gtgaaaaaag atttccccga attagaccta aaaatacgag 900 taaacaagga aaaagtaact ttcttaaatt ctcccttaga actctaccat aaaagtgtct 960 cactaattct aggactgctt caacaaatag aaaactcttt aggattattc ccagactctc 1020 ctgttcttga aaaattagag gataacagtt taaagctaaa aaaggctttg attatgctta 1080 tcttgtctag aaaagacatg ttttccaagg ctgaatagac aacttactct aacgttggag 1140 ttgatttgca caccttagtt ttttgctctt ttaagggagg aactggaaaa acaacacttt 1200 ctctaaacgt gggatgcaac ttggcccaat ttttagggaa aaaagtgtta cttgctgacc 1260 tagacccgca atccaattta tcttctggat tgggggctag tgtcagaagt gaccaaaaag 1320 gcttgcacga catagtatac acatcaaacg atttaaaatc aatcatttgc gaaacaaaaa 1380 aagatagtgt ggacctaatt cctgcatcat tttcatccga acagtttaga gaattggata 1440 ttcatagagg acctagtaac aacttaaagt tatttctgaa tgagtactgc gctccttttt 1500 atgacatctg cataatagac actccaccta gcctaggagg gttaacgaaa gaagcttttg 1560 ttgcaggaga caaattaatt gcttgtttaa ctccagaacc tttttctatt ctagggttac 1620 aaaagatacg tgaattctta agttcggtcg gaaaacctga agaagaacac attcttggaa 1680 tagctttgtc tttttgggat gatcgtaact cgactaacca aatgtatata gacattatcg 1740 agtctattta caaaaacaag cttttttcaa caaaaattcg tcgagatatt tctctcagcc 1800 gttctcttct taaagaagat tctgtagcta atgtctatcc aaattctagg gccgcagaag 1860 atattctgaa gttaacgcat gaaatagcaa atattttgca tatcgaatat gaacgagatt 1920 actctcagag gacaacgtga acaaactaaa aaaagaagcg gatgtctttt ttaaaaaaaa 1980 tcaaactgcc gcttctctag attttaagaa 2010 47 2044 DNA Chlamydia trachomatis 47 gtcatcaaga aaagattggg aacctatccg tagtttggtt aaagagcatg gtatgcgaca 60 ttgtcagctt atggctatag ctccgacagc gacgatctcc aacattatag gagtaactca 120 atctattgag ccaacgtaca aacatttgtt tgtgaagtct aatttgtccg gagaattcac 180 gattccaaat gtgtatttaa ttgagaagtt gaagaaatta ggtatctggg atgctgatat 240 gttagatgac ctgaaatatt ttgatgggtc tttattggaa atcgagcgta taccagatca 300 cttaaaacat attttcttga cagcttttga gattgaacca gaatggatta tcgaatgcgc 360 gtctcgaaga caaaaatgga ttgatatggg gcaatccctc aacctttatc ttgcccagcc 420 agacgggaaa aaactgtcga atatgtattt aacggcttgg aaaaaaggtt tgaaaactac 480 gtattatctg agatcttcat cagcaacgac cgttgaaaaa tcttttgtag atattaataa 540 gagaggaatt cagcctcgtt ggatgaagaa taagtctgct tcggcaggaa ttattgttga 600 aagagcgaag aaagcacctg tctgttcttt ggaagaaggg tgtgaagcat gtcagtaatt 660 aatcatataa attaacaata aaattaacgg ttcttatgca agcagatatt ttagatggaa 720 aacagaaacg cgttaatcta aatagcaagc gtctagtgaa ctgcaaccag gtcgatgtca 780 accaacttgt tcctattaag tacaaatggg cttgggaaca ttatttgaat ggctgcgcaa 840 ataactggct ccctacagag atccccatgg ggaaagacat cgaattatgg aagtcggatc 900 gtctttctga agatgagcgg cgagtcattc ttttgaattt aggttttttc agcaccgcag 960 agagcttggt tgggaataat attgttctag caatttttaa acatgtaact aatccggaag 1020 cgagacaata tcttttaaga caagcttttg aagaagcggt tcacacgcac acatttttgt 1080 atatttgtga gtcactcgga ttagacgaga aagaaatttt caatgcctat aacgagcgtg 1140 ctgcgattaa ggccaaagat gatttccaga tggaaatcac tggcaaggta ttggatccta 1200 attttcgcac ggactctgtt gagggtctac aggagtttgt taaaaactta gtaggatact 1260 acatcattat ggaagggatt ttcttctata gtgggtttgt gatgatcctt tccttccaca 1320 gacaaaataa gatgattggt attggagaac aatatcaata catcttaaga gatgagacaa 1380 tccacttgaa ctttggtatt gatttgatca acgggataaa agaagagaac ccggggattt 1440 ggactccaga gttacagcaa gaaattgtcg aattaattaa gcgagctgtc gatttagaaa 1500 ttgagtatgc gcaagactgt ctccctagag ggattttggg attgagagct tcgatgttca 1560 tcgattatgt gcagcatatt gcagaccgtc gtttggaaag aatcggatta aaacctattt 1620 atcatacgaa aaacccattc ccttggatga gcgaaacaat agaccttaat aaagagaaaa 1680 acttctttga aacaagggtt atagaatatc aacatgcagc aagcttaact tggtagtcct 1740 gatatcaaaa taggagaaag cctcaaccat agagttgagg cttttttttg tcatacggta 1800 acctgataag aatttttaga ttttcaggtt agaagtaaat gtatttaccc atgaattttt 1860 tttaattttc tcataatatc ttgtagccct tttattaaaa tggaaaaggc tagtcacctc 1920 tcctatgact actgttagag tggtgagatt tggggttgga gcaggtgtag cctttcgcat 1980 acgaagtatt ttcctgtgaa accacaagat ttgaaacttc cctatttttg ggaagaacgt 2040 tctc 2044 48 3734 DNA Chlamydia trachomatis 48 gttattcgct tctactccat tagaagtccc taatgctaaa ctcaccattt ttcctccttt 60 ccgttaaaac aggaaagaaa ttgtacagaa acattttttt aaagaaatca aaaagccatt 120 tgcaggcaga tatcaggcca tttatatcaa aaacagaaag aatgattagg ataaaacttt 180 gtcttgccat cgttccagag agcattgaga agccgttttt attataaata cattgcacta 240 agaatcttaa aatcgaacag acaacacaat ggctcgaaca gactgatcca cacgcactaa 300 ttcaaatgca aaaaacttct aaaatgaaca cagcaagctt gataaaaaca tataaaagaa 360 ttggatcata gagctttacg agaaggggcg cactgcaatc tgtctcgacc aaatagcaat 420 gcaaacagat aaatacccct aatcattggg aaaaattgag tgtagaatag cctctttctc 480 ttcctctatt tgttgcttag ctaacgcgat ttcttcttta gagatatctg caagtctctg 540 cttatccaaa aagccttgtc tctcattttc caatacaaat ctgtccagag aaactttttt 600 tggctctcca ccatagctag aaattctagt aagaacagca cctagcatca cagatccaaa 660 aacaaccagg gtaaccacta cgtcaatcat aggaagcgta gtccaacctg ccccaataaa 720 taaggctgct cctgtaacta tgaataaaat actaagaata ccgagcgcaa gcacagcaat 780 acgttcgcta caacaagaaa ctctcgcttt agaagcgcta tccaccaaag gagcctctgg 840 catataactt ctaagaggta cactatctcc aacaaaactc atggcatccc ccttaaggta 900 aaagagaagc tttcctctaa atagaaaagc gtatcgtcaa ctcttttata gatctaaaaa 960 gtcttgcttt ccttaatccc acccatgaaa tttagcataa aaaccatcca acatattcac 1020 acgctcttct aaaaggccta tttccctatt tttctgagtc tctaaaaccc tataatggct 1080 ggaaattttc cgcgcacttt ccttggcttc ttgtaatagc tgatctgaat tgcgtatcac 1140 agataacagg taagaaacta atccaaaagc tcctatacaa gaaccaataa ttgcagctct 1200 cccactactc ctaaaactaa ggaagaatag actcccccaa gacaaagaaa aactcctcct 1260 aaagctgcaa gcaaacttgt tagaacaact acaaataact ggtatgtttt agaacggtga 1320 ataaaggagt tgttagccac attttcactg tacctcagtt tttgctgaac aacaattccc 1380 taaaaaattg gtaggacgcc aaacgttcat aattactcta cttggaaacc attaataatt 1440 atatcagact ttcttccaat acacatttca acccactttg aagctgttct atttttttct 1500 gagcaagctc taaatctttg ctcttttgag caagcaatcc ttcaacttct ttcaaatctt 1560 cttctgcttc atatagaagt tcttgataag ataacactaa tccaggagtc acggcctctg 1620 gagctaactc agatgactct gaagggagtc tcgtcggttt taaagaaaac ccatacatat 1680 aaactagact tcctcctata caggcagaac ccagtgtcat tgctaataag ctaagaatag 1740 gagcaaaaag agagaccaca cttcctgaaa aaagaagcag aagagcacca cctaaaactg 1800 ctagtacccc taataccaag gcacctattg ccaacaattg ctctttacgg cttgtagtag 1860 tctgagcacc gatagtttca gtatgatcgg cacgcaatgg tttgctggaa ttacaacaaa 1920 aagaaatatt aaacatggcg cctctatttc gcaaaaaaaa ggccaacatg ctacaggaaa 1980 gctaattaaa gtaaaaattt ttatatattt caatggtagt taaataccta atctacccaa 2040 ccaaaagatg tctaaatgac aaaaaaataa tcgtatttat attatcatga gacacttata 2100 gtcacgtctg cttcattcag ctcaaattct aatgaaaaat cggatttaga agaaaataga 2160 ctcgaagagt cagaactagc caaaatgttt gttctaattc tattttgcaa tccccgacta 2220 caagaccaat agagaaacgt taaccctact cctaaagcca cagaaccaat cataatcgct 2280 ccaataccta aaccggcaaa cacaagcgac gatcccccgc aaagcaaaca aagcaaggct 2340 acacaactta aaatagcaaa aattcctaag gaaacggcaa attctatatt tcctcttcgt 2400 ttgcaataaa tatgcgtctt atacagacac aactctgcgg ggctctccag agttggagcg 2460 caagaggaac aaaaaagata agacattgtc gactccggac caaaaaaagg cgagataata 2520 cgcgagatgg taaaaataca gaaatatttt tgacatagaa aaccctaacc ctcctttcat 2580 cgcgtgagac tagagtgtaa aacaagatgc gaaagcaagg ttcgctatgt ttggaaacaa 2640 acctccacac ggtcccggat tatcaaaaca agtcttccag ggatatgtta gagaacgtcc 2700 tatccatacc aaagcaacat atagacgtct tttgtgaaaa gactgaatag aggaatctaa 2760 gaagcttggt tagcgtctat agatgcttta agagcagctt tttccttttc agcactatcc 2820 aaccatcttg tgtagctaga taaaactaag cgcacatcgg acaataaagc ttgctcattt 2880 ttctctaatc tgtccaaaca atcaatctca acttctattg ccttagcttc caaagcttgg 2940 agatcgtccg taagacctcg cagaaacatc ttattaatga aagagacgga gaccaaagcg 3000 tccttctctt ctgaaagatt acgcaaacgt tgctcagcca aaacattttt tgcttctaag 3060 ctagcataag aggatcgaca cataagacga gatattcccg cacccacaca agcagatcca 3120 ataattaatg cagcaatacc tattgcagta aatatgacat tgctagcgca caaaaccaaa 3180 gctaataccc cagcgacaac aactaaagcg cctacgatag ctaaagctat atccaaaatt 3240 ttggaacaag tattcccttt tgttgaagac gaagtagatt ttatctctac gcaggaagct 3300 gttggcaatg gtaaagaaga agcgtctccg ctaatagtag tactcatttt tccacatttt 3360 tatttttaaa acggaaaaac tgtatcagaa cggcgcttta ttcgcaaatc attataaatc 3420 cgcaacatgc agaactaaag cgccgtaagc aaaaggaacc cctaactctc agatgcaata 3480 tctgaggagt ctttaattat tttttacgac gggatgcctg cacctgcagc cgctctgata 3540 atgtcttatt ctcagatctc aatttacaca actctgctgt taattgactg caagtgttct 3600 gactttgttg caaccgctgt ttaaaccctt ctgtctgatg acgaatttct tgttcagcat 3660 cctcctcaat ggagcaaact gtttcggcat aacgcttaca caaatctaat atttgttctt 3720 ccaactcttg gcaa 3734 49 2937 DNA Chlamydia pneumoniae 49 atgcctcttt ctttcaaatc ttcatctttt tgtctacttg cctgtttatg tagtgcaagt 60 tgcgcgtttg ctgagactag actcggaggg aactttgttc ctccaattac gaatcagggt 120 gaagagatct tactcacttc agattttgtt tgttcaaact tcttgggggc gagtttttca 180 agttccttta tcaatagttc cagcaatctc tccttattag ggaagggcct ttccttaacg 240 tttacctctt gtcaagctcc tacaaatagt aactatgcgc tactttctgc cgcagagact 300 ctgaccttca agaatttttc ttctataaac tttacaggga accaatcgac aggacttggc 360 ggcctcatct acggaaaaga tattgttttc caatctatca aagatttgat cttcactacg 420 aaccgtgttg cctattctcc agcatctgta actacgtcgg caactcccgc aatcactaca 480 gtaactacag gagcctctgc tctccaacct acagactcac tcactgtcga aaacatatcc 540 caatcgatca agttttttgg gaaccttgcc aacttcggct ctgcaattag cagttctccc 600 acggcagtcg ttaaattcat caataacacc gctaccatga gcttctccca taactttact 660 tcgtcaggag gcggcgtgat ttatggagga agctctctcc tttttgaaaa caattctgga 720 tgcatcatct tcaccgccaa ctcctgtgtg aacagcttaa aaggcgtcac cccttcatca 780 ggaacctatg ctttaggaag tggcggagcc atctgcatcc ctacgggaac tttcgaatta 840 aaaaacaatc aggggaagtg caccttctct tataatggta caccaaatga tgcgggtgcg 900 atctacgccg aaacctgcaa catcgtaggg aaccagggtg ccttgctcct agatagcaac 960 actgcagcga gaaatggcgg agccatctgt gctaaagtgc tcaatattca aggacgcggt 1020 cctattgaat tctctagaaa ccgcgcggag aagggtggag ctattttcat aggcccctct 1080 gttggagacc ctgcgaagca aacatcgaca cttacgattt tggcttccga aggtgatatt 1140 gcgttccaag gaaacatgct caatacaaaa cctggaatcc gcaatgccat cactgtagaa 1200 gcagggggag agattgtgtc tctatctgca caaggaggct cacgtcttgt attttatgat 1260 cccattacac atagcctccc aaccacaagt ccgtctaata aagacattac aatcaacgct 1320 aatggcgctt caggatctgt agtctttaca agtaagggac tctcctctac agaactcctg 1380 ttgcctgcca acacgacaac tatacttcta ggaacagtca agatcgctag tggagaactg 1440 aagattactg acaatgcggt tgtcaatgtt cttggcttcg ctactcaggg ctcaggtcag 1500 cttaccctgg gctctggagg aaccttaggg ctggcaacac ccacgggagc acctgccgct 1560 gtagacttta cgattggaaa gttagcattc gatccttttt ccttcctaaa aagagatttt 1620 gtttcagcat cagtaaatgc aggcacaaaa aacgtcactt taacaggagc tctggttctt 1680 gatgaacatg acgttacaga tctttatgat atggtgtcat tacaatctcc agtagcaatt 1740 cctatcgctg ttttcaaagg agcaaccgtt actaagacag gatttcctga tggggagatt 1800 gcgactccaa gccactacgg ctaccaagga aagtggtcct acacatggtc ccgtcccctg 1860 ttaattccag ctcctgatgg aggatttcct ggaggtccct ctcctagcgc aaatactctc 1920 tatgctgtat ggaattcaga cactctcgtg cgttctacct atatcttaga tcccgagcgt 1980 tacggagaaa ttgtcagcaa cagcttatgg atttccttct taggaaatca ggcattctct 2040 gatattctcc aagatgttct tttgatagat catcccgggt tgtccataac cgcgaaagct 2100 ttaggagcct atgtcgaaca cacaccaaga caaggacatg agggcttttc aggtcgctat 2160 ggaggctacc aagctgcgct atctatgaac tacacggacc acactacgtt aggactttct 2220 ttcgggcagc tttatggaaa aactaacgcc aacccctacg attcacgttg ctcagaacaa 2280 atgtatttac tctcgttctt tggtcaattc cctatcgtga ctcaaaagag cgaggcctta 2340 atttcctgga aagcagctta tggttattcc aaaaatcacc taaataccac ctacctcaga 2400 cctgacaaag ctccaaaatc tcaagggcaa tggcataaca atagttacta tgttcttatt 2460 tctgcagaac atcctttcct aaactggtgt cttcttacaa gacctctggc tcaagcttgg 2520 gatctttcag gttttatttc cgcagaattc ctaggtggtt ggcaaagtaa gttcacagaa 2580 actggagatc tgcaacgtag ctttagtaga ggtaaagggt acaatgtttc cctaccgata 2640 ggatgttctt ctcaatggtt cacaccattt aagaaggctc cttctacact gaccatcaaa 2700 cttgcctaca agcctgatat ctatcgtgtc aaccctcaca atattgtgac tgtcgtctca 2760 aaccaagaga gcacttcgat ctcaggagca aatctacgcc gccacggttt gtttgtacaa 2820 atccatgatg tagtagatct caccgaggac actcaggcct ttctaaacta tacctttgac 2880 gggaaaaatg gatttacaaa ccaccgagtg tctacaggac taaaatccac attttaa 2937 50 801 DNA Chlamydia pneumoniae 50 atgcattcaa aatttctttc tcgaagaaaa aaaaatagtt ctcataagga ggaaacctct 60 tgggattgta tagcctcaag ttacaataag atagtccaag ataaagggca ctactatcat 120 agagaaacta tccttcccca actcctgcct tcactcacct taggttcaaa aagttctgta 180 ttggatattg gctgcggtca aggtttttta gaaagggccc ttcctaagga atgtcgttat 240 ctaggcatag atatctcttc tagattgatt gctctagcaa agaaaatgcg atcggtaaac 300 tctcatcagt ttaaggttgc agatcttagc aaacgcctag agttcgtaga accgacatta 360 ttctctcatg cagtagcaat cctctccctt caaaatatgg aattccccgg agaggctata 420 cgtaatacag ctacgctcct cgaaccactc gggcaatttt ttatagtttt aaaccatcct 480 tgttttcgta ttcctagggc atcatcctgg cactatgatg aaaataaaaa agctatctct 540 cgtcatatag atcgttatct ctccccaatg aaaatcccaa tcatggctca cccaggacaa 600 aaagattcgc cttctaccct ctcctttcac tttcctctaa gctattggtt taaagaactg 660 tcttctcatg gattcttagt ttcaggtctt gaggaatgga catcttcaaa aacctcaaca 720 ggaaaacgag ctaaggcaga aaacctttgt cgaaaggaat ttccattatt ccttatgatt 780 tcatgcatta agataaaata a 801 51 252 DNA Chlamydia pneumoniae 51 atgaaacaac aacacaatcg taaggcttta tctcgcaaga ttggcacagt gaaaaaacaa 60 gccaaatttg caggaagctt tttagatgag attaaaaaaa ttgaatgggt aagcaagcac 120 gatcttaaga aatacataaa agtagttctt atcagtattt ttggttttgg atttgctatt 180 tatttcgtag atcttgtgtt gcgtaagtca atcacatgtt tagatggtat aacaaccttt 240 ttgttcggtt aa 252 52 1185 DNA Chlamydia pneumoniae 52 atgtcaaaag aaacttttca acgtaataag ccccatatca atattgggac gatcgggcac 60 gttgaccatg gtaaaactac gctaacagcg gcaattacac gcgcgctatc aggggatgga 120 ttggcctctt tccgtgacta tagttcaatt gacaatactc cagaagaaaa ggctcgtgga 180 attactatca acgcttctca cgttgaatac gaaaccccaa atcgtcacta cgctcacgta 240 gactgccctg gtcacgctga ctatgttaaa aatatgatta caggcgccgc tcaaatggac 300 ggagctatcc tagtcgtttc agctacagac ggagctatgc cacaaactaa agaacatatc 360 ttgctagctc gccaggttgg agttccttat atcgttgttt tcttgaataa agtagatatg 420 atctctcaag aagatgctga acttattgac cttgttgaga tggaacttag tgagcttctt 480 gaagaaaaag gctacaaagg atgccctatt atccgtggtt ctgctttgaa agctcttgaa 540 ggtgatgcaa attatatcga aaaagttcga gaacttatgc aagctgtgga tgacaacatc 600 cctacaccag aaagagaaat tgataagcct ttcttaatgc ctatcgaaga cgtattctca 660 atctctggtc gtggtactgt ggttacagga agaatcgagc gtggaatcgt taaagtttct 720 gataaagttc agctcgtggg attaggagag actaaagaaa caatcgttac tggagtcgaa 780 atgttcagga aagaacttcc tgaaggtcgt gcaggagaaa acgttggttt actcctcaga 840 ggtattggaa agaacgatgt tgaaagaggt atggtggttt gtcagcctaa cagcgtgaag 900 cctcatacga aatttaagtc agctgtttac gttcttcaga aagaagaagg cggacgtcat 960 aagcctttct tcagcggata cagacctcag ttcttcttcc gtactacaga cgtgacagga 1020 gtcgtaactc ttcctgaagg aactgaaatg gtaatgcctg gagataacgt tgagcttgat 1080 gttgagctca ttggaacagt tgctcttgaa gaaggaatga gatttgcaat tcgtgaaggt 1140 ggtcgtacta tcggcgctgg aacgatttca aagatcaatg cttaa 1185 53 1431 DNA Chlamydia pneumoniae 53 atgagaatcg tacaagtcgc tgtagaattc actccaatcg ttaaagtagg cggtctaggc 60 gatgctgtag ctagtctatc taaggagtta gcgaaacaaa atgatgtgga agtacttctc 120 cctcattatc ctttaatttc caaattctct tcgtctcaag ttctttccga gcgttctttc 180 tattatgaat ttttaggcaa gcagcaagcc tctgcaattt cttattctta cgagggtctt 240 acgcttacta taattacgtt ggattcacaa atagagcttt tctcaaccac gtccgtgtac 300 tctgagaata atgttgtacg tttctctgct tttgcagctg cagctgcagc ttatcttcaa 360 gaagcggatc ctgctgacat tgtgcacttg catgactggc atgtaggttt acttgcgggt 420 ttattaaaaa accctttaaa ccctgtgcat tcgaagattg tctttactat ccataatttt 480 ggttatcgag ggtattgtag tacgcagcta ttagcagcgt cgcaaattga tgattttcat 540 ttgagtcact accaactatt tcgcgatccg caaacttctg ttctaatgaa gggagctctc 600 tattgttcgg attacattac gacagtgtct cttacttatg tgcaggaaat tataaacgac 660 tattctgatt acgaacttca tgatgcgatt ctagcaagaa attctgtatt ttctgggatc 720 atcaatggca ttgatgaaga cgtttggaac ccgaagacag atcctgcttt agctgtacag 780 tacgatgcaa gcctattaag cgaacctgac gttctcttta ctaaaaaaga agagaacaga 840 gcggtattat atgagaagtt ggggatcagt tcagactatt ttcctttgat ttgtgtgatc 900 tcacgcattg ttgaggaaaa gggtcctgaa tttatgaaag agattattct ccatgctatg 960 gagcacagtt atgcctttat cttgattggg acaagtcaaa atgaggttct tcttaatgag 1020 ttccgtaact tacaagattg tttagcgagc tcccccaaca ttcgtttgat cttggacttt 1080 aatgatcctt tagccaggct aacttatgct gctgccgata tgatctgcat cccttcacat 1140 agggaggctt gtggacttac ccagctgata gcgatgcgtt atggcacagt tcctttagtt 1200 cgtaaaactg gagggcttgc tgatacagtg attcctgggg taaatggttt cactttcttt 1260 gatacaaaca attttaatga atttcgggct atgcttagca acgctgtaac gacgtatcgt 1320 caggagcctg acgtttggtt gaatttgatt gagtcgggaa tgcttcgggc ctctggctta 1380 gatgccatgg ctaagcatta cgtaaatctt tatcaatctt tactctcatg a 1431 54 1041 DNA Chlamydia pneumoniae 54 atggaagcag atattttaga tggaaagctc aaacgggttg aggtaagtaa aaaaggattg 60 gtgaattgta atcaagtaga tgtcaatcag ctagtcccta tcaagtataa atgggcttgg 120 gaacattacc tcaatggatg tgcaaacaac tggcttccta ctgaagttcc tatggcaaga 180 gatatcgagt tgtggaaatc agatgaactg tctgaagacg aacgcagggt cattttgtta 240 aacctaggat ttttcagtac cgcggaaagc ctagtcggaa ataacatcgt tcttgctatc 300 ttcaaacata tcacaaaccc tgaagcaaga cagtatttac tgcgtcaagc ttttgaggaa 360 gccgtacata cacatacatt tctctatatt tgcgaatctt taggacttga tgaaggcgaa 420 gtattcaatg cctataatga aagagcctca attagggcta aagatgattt tcaaatgaca 480 ttaacagtcg atgtccttga tcctaatttt tctgtacagt cttcagaagg ccttgggcag 540 ttcattaaaa acttagtagg atactatatc attatggaag gaatcttctt ctatagtggt 600 tttgtaatga ttctctcttt ccatagacaa aataaaatga caggaattgg agaacagtac 660 caatacatcc tcagagatga aaccatacat ttaaattttg gaatcgatct tatcaatgga 720 attaaagaag aaaaccccga agtttggact acggaactac aagaagaaat cgtcgctctt 780 attgaaaaag ctgtagagct tgaaattgag tacgctaaag attgcttacc tcgaggaatc 840 ttgggattaa gatcttcgat gtttatagat tacgttcgtc atattgcaga tcgtcgttta 900 gagagaattg ggttgaagcc tatctatcac tccagaaatc ctttcccttg gatgagcgaa 960 accatggatc tgaataaaga aaagaatttc tttgaaaccc gggttaccga ataccaaacc 1020 gctggtaatt taagttggta a 1041 55 3135 DNA Chlamydia pneumoniae 55 atggtcgaag ttgaagaaaa gcattacacc atcgtcaaac gtaatggaat gtttgtccca 60 tttaatcaag atcggatttt ccaggctttg gaggcagctt ttcgagatac gcgtagctta 120 gaaactagtt ctccactacc taaagactta gaagaatcta ttgcgcaaat tactcataaa 180 gtcgtgaagg aagtcctcgc taaaatttca gaaggtcagg tagtcactgt agagagaatc 240 caggatcttg tagaaagtca gctctatatt agcgggttgc aggatgtggc tcgcgattat 300 attgtttaca gggaccaacg caaggcagag cgcggtaact cttcgtccat aattgccatc 360 atacgtagag acgggggaag cgctaaattt aatcctatga agatctctgc agctctcgaa 420 aaagcattca gagcgacgct ccaaattaat gggatgactc ctcctgcaac actatccgaa 480 attaatgacc ttacccttag gatcgttgaa gatgtcctaa gccttcatgg tgaagaagct 540 attaatctgg aagagatcca agatattgtt gaaaagcaac ttatggttgc cggctattat 600 gatgtggcca agaattatat tttatataga gaagctcgtg cacgagcccg tgctaataaa 660 gatcaagatg gacaagaaga gtttgtcccc caagaggaaa cgtacgttgt tcaaaaagaa 720 gacggcacca cctaccttct gagaaaaaca gatttagaaa agaggttttc ttgggcatgc 780 aaacgctttc ctaaaactac agattctcaa ctgcttgcag atatggcatt tatgaatttg 840 tattcaggaa tcaaagaaga cgaggtcacc acagcatgca tcatggcggc acgtgccaat 900 atcgagagag aacctgatta cgcttttatc gcagcagaac tcctcacgag ttccttgtat 960 gaagagacct taggatgcag ctctcaagac cccaatttat cagaaataca taaaaaacat 1020 tttaaagaat acatcctcaa tggagaagag tatcgcttga atcctcaatt aaaggattat 1080 gatctcgatg ctcttagtga agtcctagac ctctctagag accaacagtt ttcctatatg 1140 ggagtccaaa atctctacga tcgctatttt aatctgcatg aaggacgacg tttagagact 1200 gcgcagatct tttggatgcg ggtttctatg ggcttagcct taaatgaagg agaacaaaag 1260 aatttttggg caatcacttt ctataatctg ttatccacat tccgctatac cccagcaact 1320 cctacattgt ttaactccgg aatgcgtcat tcccaactca gttcatgcta tctttccaca 1380 gtaaaagatg acctaagtca catttataag gtgatttctg ataatgcttt gctttctaaa 1440 tgggcagggg gaattggaaa tgattggaca gatgtccgtg ctacaggagc tgtaattaag 1500 ggaaccaatg gaaagagtca aggcgtcatt cccttcatta aggttgccaa tgatactgca 1560 attgcagtga atcagggggg caaacgtaaa ggtgctatgt gcgtatattt agaaaactgg 1620 cacttggatt acgaagactt tttagaattg cggaagaata caggagatga gcgtcgtaga 1680 actcacgata tcaatacagc aagctggatt cctgatctct tctttaagag actagaaaaa 1740 aaaggcatgt ggacactctt tagccccgat gatgtcccag gtttacacga agcctatggg 1800 ttagagtttg aaaagcttta tgaagaatat gaacgtaagg ttgaatctgg ggaaatccgt 1860 ctttataaaa aagtagaagc cgaagtgctg tggcgtaaaa tgttaagcat gctttacgaa 1920 acagggcatc cttggattac atttaaagat ccttcgaata ttcgctcaaa ccaagatcat 1980 gttggcgtcg tacgctgttc taatctatgt acagagattt tattgaactg ttcggaatca 2040 gagactgcag tttgtaattt aggttccata aacttggtag aacatatccg taatgacaag 2100 ttagatgaag aaaaattaaa agaaactatc tcaatagcca tccgtatttt ggataacgtt 2160 attgacctga acttctaccc tacaccagag gctaaacaag ccaacctaac tcacagagct 2220 gtggggttgg gggttatggg attccaggat gttctttacg agttgaacat tagctatgcc 2280 tcacaagaag ctgtcgaatt ttctgacgag tgctcggaga tcatcgcata ctacgctatt 2340 ctagcctcga gcttactcgc gaaagaacga ggtacatatg cttcttattc aggatctaag 2400 tgggatcgtg ggtatctacc cttagatact atcgagcttc tcaaagaaac tcgcggagag 2460 cataatgttc ttgtagacac atcaagtaaa aaagattgga ctccagttcg tgatactatc 2520 cagaaatacg gaatgagaaa tagccaggtc atggcaattg ctcctacagc aacgatctcg 2580 aatatcatag gggtcaccca atctatagag cccatgtata aacatctctt tgtaaagtcc 2640 aacctttccg gagagtttac gatccccaac acctacctga ttaaaaaact taaggaatta 2700 ggactttggg atgcagaaat gttagatgat ctaaaatatt ttgacggatc tctattggaa 2760 attgaaagga tccctaatca cttgaaaaag cttttcctta cggcatttga aatcgaaccc 2820 gagtggatta tagagtgtac ctctagaaga cagaaatgga ttgatatggg agtttctcta 2880 aatctgtatc ttgctgagcc agatggtaaa aaactctcca atatgtatct cacggcttgg 2940 aaaaaaggat taaagactac ctattattta agatctcaag ctgcaacatc agtagagaaa 3000 tcatttatag atatcaataa acgcggcatt cagcctcgtt ggatgaaaaa taaatcagcg 3060 tccacaagta ttgtggtcga aagaaaaaca acccccgttt gttcaatgga agaaggttgc 3120 gaatcttgtc aataa 3135 56 1386 DNA Chlamydia pneumoniae 56 atgatgagct ctaagcgtac ctcgaaaata gcggtgcttt caattttatt aacatttact 60 cactctatag ggttcgcaaa tgcgaattcg tccgtaggtc ttggcacggt ctacattaca 120 tccgaggttg taaagaagcc tcagaaagga tcagaaagga aacaagccaa aaaagaacct 180 cgtgctcgta aaggatactt agtcccttct tcaaggactc tttcagctcg agcccaaaag 240 atgaaaaact cctctcgtaa agagtcttca ggtggttgta acgaaatttc tgcaaattct 300 acacccagat ctgtaaaatt acgaagaaac aaacgtgcag aacaaaaggc agctaaacaa 360 ggattttcag ctttttctaa cctaactttg aaaagcctac ttcctaaact tccttcaaaa 420 caaaaaactt caattcacga gagagaaaaa gcaacctcaa gatttgttaa tgagtctcag 480 cttagttccg cacgaaaacg ctactgcaca ccatcttcag ccgctccttc cctattttta 540 gaaacagaaa tcgttcgagc tcctgtagaa agaactaaag aacttcaaga taatgaaatt 600 catattcctg tagtgcaagt ccaaacgaac cccaaagaac aaaatacaaa gacaactaaa 660 cagttggcat cccaagcctc gattcaacaa tctgaaggaa ccgagcaatc attgcgagag 720 ctcgcccaag gtgctagcct acctgtctta gtgcgctcta atcctgaagt gtctgtacaa 780 agacaaaaag aagagttatt aaaagaactc gtagctgaac gtagacaatg taaaagaaag 840 tctgtaagac aagctcttga agctcgttct ttaactaaga aagttgctag aggcggttct 900 gtgacctcga ctttacgata cgatccagaa aaagcggcgg aaatcaaaag tagacgcaat 960 tgcaaagtaa gtcctgaagc acgtgaacaa aaatattcat cttgcaaaag agatgctcgc 1020 gctaatggga aacaagacaa gacaactcct agtgaagatg cttctcaaga agaacaacaa 1080 actggggcag gactcgtacg caagactcct aaatctcagg ttgcaagtaa tgctcagaac 1140 ttctaccgaa attctaaaaa tacaaacata gatagctatc ttacagctaa ccaatacagc 1200 tgtagttctg aagaaacaga ttggccatgt tcttcctgcg tctctaaacg cagaactcac 1260 aacagtatat ctgtatgtac catggtagtt actgtcattg cgatgatcgt aggggctttg 1320 attatagcta atgctacaga atctcaaaca acatcagatc caactcctcc aactcctact 1380 ccatag 1386 57 1731 DNA Chlamydia pneumoniae 57 atgacagatt ttcctactca cttcaaagga cccaaactta accccattaa agtaaatcca 60 aacttttttg agaggaatcc taaagtcgca agggtactgc aaattacagc cgtagtctta 120 ggaatcattg ccctcttatc cggtatagta ctcattatag gcacccctct cggagctcct 180 ataagtatga tcctcggcgg atgtctttta gcttctggag gcgccttatt tgttggtggt 240 acgattgcta cgatattgca agctagaaat agttataaga aggccgtgaa ccaaaagaaa 300 ctctcagagc ctttgatgga acgccccgaa ttgaaagcct tagattattc cctagatctg 360 aaagaggtat gggacctaca tcattctgtt gtcaaacatc ttaaaaaatt agacctgaat 420 ctttccaaaa cccaaaggga agttctaaat caaatcaaaa ttgatgatga gggaccctcc 480 ctaggggaat gcgccgctat gatttcagaa aactacgacg catgcttaaa gatgctcgcg 540 tatcgtgagg agctcctgaa agaacaaacc caataccaag agacacgatt caatcagaac 600 ctcactcata gaaataaagt tttgctctcc atcctctcaa ggatcacgga caatatttct 660 aaagcgggcg gggtcttttc tttgaaattt tccacgctaa gctcgcggat gtcacgaatt 720 cataccacca ccactgtgat tctggcttta agtgccgttg tttctgtcat ggtcgtagca 780 gctctaattc caggtggcat tttagcacta cctatacttt tggctgttgc tatttctgca 840 ggagtgattg tcaccggact ttcctatcta gttcgtcaga ttttaagtaa caccaagcgt 900 aatcgtcagg atttttataa agattttgta aaaaatgtag atatagagct tcttaaccaa 960 acggtaactt tacagcgatt cctctttgaa atgctcaaag gtgttctgaa agaagaagaa 1020 gaagtctcct tagaaggtca agattggtat acacaataca taaccaatgc acccatagaa 1080 aaaagattga tcgaagagat cagagttacc tacaaagaga tcgatgctca gaccaaaaaa 1140 atgaagacag acttggagtt cttagaaaat gaggtgcgtt ccgggagact gtctgtagcg 1200 tccccgtcgg aagatccaag tgaaactcct atttttactc aaggtaagga gtttgcaaag 1260 ttacgtcgcc aaacctctca gaatatatcc acgatttatg gtccggacaa tgaaaatatt 1320 gatcccgaat tttccttacc ctggatgcct aaaaaagaag aagaaataga ccatagctta 1380 gaacctgtta caaagttgga acccggttca agagaagagt tgttgttggt agagggggtc 1440 aacccaacct taagagaact caatatgaga attgcacttc tacaacaaca actatcaagt 1500 gtccgaaaat ggagacaccc tcgaggggaa cattacggga atgttatcta ttcagataca 1560 gaactcgatc gtattcagat gctagaaggc gcattttata atcacctcag ggaagctcaa 1620 gaggaaatca cccagtctct cggagacctt gttgacattc aaaaccgtat tttagggatc 1680 atagttgaag gggactcaga ttcaagaaca gaagaagagc ctcaggaata g 1731 58 1086 DNA Chlamydia pneumoniae 58 atgcaacaaa ctgtaattgt agcaatgtca ggaggcgtgg attcttctgt cgttgcctat 60 ttattcaaaa aatttaccaa ttataaggtt attggcctct tcatgaagaa ttgggaagag 120 gatagcgaag gcggcctttg ctcgtctact aaagattatg aagatgtcga gagggtatgt 180 cttcagctcg atatccctta ttacaccgta tcttttgcta aagaatatag agaaagagtg 240 ttcgctcgtt tcctcaagga atactcttta ggctacactc ctaaccccga cattctttgt 300 aaccgagaaa tcaaatttga ccttctacaa aagaaagtcc aggaacttgg cggagattac 360 ctcgctacag ggcactactg ccgattaaat accgagctcc aagaaaccca actccttaga 420 ggttgcgatc ctcaaaaaga tcagagctat tttttatcag gaactcctaa aagtgctctt 480 cacaatgtgc tctttcctct tggggaaatg aataagactg aagttcgtgc gattgcagct 540 caagcagctc ttcccacagc agaaaaaaaa gatagtacag gcatttgctt tatagggaag 600 cgccctttta aagagttcct agagaagttt cttcccaata aaacaggcaa cgttatcgat 660 tgggatacca aggaaattgt agggcaacat cagggagctc actattatac tatagggcag 720 cggcgaggac ttgatcttgg aggatccgag aaaccctgtt atgttgtggg aaaaaatata 780 gaggaaaata gcatttatat tgtgaggggg gaagaccatc cccagctcta cctacgggaa 840 ttaacagcta gagagctcaa ttggtttacc cctcctaaat ccggatgtca ctgtagcgct 900 aaagtccgct accgttctcc tgatgaagct tgcacgatag attatagctc aggtgacgag 960 gtcaaggtgc gattttcaca acccgtcaag gcggtaactc caggacaaac aatagcgttt 1020 tatcaaggag atacctgcct tggtagtgga gttatcgacg ttcctatgat tccaagtgag 1080 ggctag 1086 59 4830 DNA Chlamydia pneumoniae 59 atggtagcga aaaaaacagt acgatcttat aggtcttcat tttctcattc cgtaatagta 60 gcaatattgt cagcaggcat tgcttttgaa gcacattcct tacacagctc agaactagat 120 ttaggtgtat tcaataaaca gtttgaggaa cattctgctc atgttgaaga ggctcaaaca 180 tctgttttaa agggatcaga tcctgtaaat ccctctcaga aagaatccga gaaggttttg 240 tacactcaag tgcctcttac ccaaggaagc tctggagaga gtttggatct cgccgatgct 300 aatttcttag agcattttca gcatcttttt gaagagacta cagtatttgg tatcgatcaa 360 aagctggttt ggtcagattt agatactagg aatttttccc aacccactca agaacctgat 420 acaagtaatg ctgtaagtga gaaaatctcc tcagatacca aagagaatag aaaagaccta 480 gagactgaag atccttcaaa aaaaagtggc cttaaagaag tttcatcaga tctccctaaa 540 agtcctgaaa ctgcagtagc agctatttct gaagatcttg aaatctcaga aaacatttca 600 gcaagagatc ctcttcaggg tttagcattt ttttataaaa atacatcttc tcagtctatc 660 tctgaaaagg attcttcatt tcaaggaatt atcttttctg gttcaggagc taattcaggg 720 ctaggttttg aaaatcttaa ggcgccgaaa tctggggctg cagtttattc tgatcgagat 780 attgtttttg aaaatcttgt taaaggattg agttttatat cttgtgaatc tttagaagat 840 ggctctgccg caggtgtaaa cattgttgtg acccattgtg gtgatgtaac tctcactgat 900 tgtgccactg gtttagacct tgaagcttta cgtctggtta aagatttttc tcgtggagga 960 gctgttttca ctgctcgcaa ccatgaagtg caaaataacc ttgcaggtgg aattctatcc 1020 gttgtaggca ataaaggagc tattgttgta gagaaaaata gtgctgagaa gtccaatgga 1080 ggagcttttg cttgcggaag ttttgtttac agtaacaacg aaaacaccgc cttgtggaaa 1140 gaaaatcaag cattatcagg aggagccata tcctcagcaa gtgatattga tattcaaggg 1200 aactgtagcg ctattgaatt ttcaggaaac cagtctctaa ttgctcttgg agagcatata 1260 gggcttacag attttgtagg tggaggagct ttagctgctc aagggacgct taccttaaga 1320 aataatgcag tagtgcaatg tgttaaaaac acttctaaaa cacatggtgg agctatttta 1380 gcaggtactg ttgatctcaa cgaaacaatt agcgaagttg cctttaagca gaatacagca 1440 gctctaactg gaggtgcttt aagtgcaaat gataaggtta taattgcaaa taactttgga 1500 gaaattcttt ttgagcaaaa cgaagtgagg aatcacggag gagccattta ttgtggatgt 1560 cgatctaatc ctaagttaga acaaaaggat tctggagaga acatcaatat tattggaaac 1620 tccggagcta tcactttttt aaaaaataag gcttctgttt tagaagtgat gacacaagct 1680 gaagattatg ctggtggagg cgctttatgg gggcataatg ttcttctaga ttccaatagt 1740 gggaatattc aatttatagg aaatataggt ggaagtacct tctggatagg agaatatgtc 1800 ggtggtggtg cgattctctc tactgataga gtgacaattt ctaataactc tggagatgtt 1860 gtttttaaag gaaacaaagg ccaatgtctt gctcaaaaat atgtagctcc tcaagaaaca 1920 gctcccgtgg aatcagatgc ttcatctaca aataaagacg agaagagcct taatgcttgt 1980 agtcatggag atcattatcc tcctaaaact gtagaagagg aagtgccacc ttcattgtta 2040 gaagaacatc ctgttgtttc ttcgacagat attcgtggtg gtggggccat tctagctcaa 2100 catatcttta ttacagataa tacaggaaat ctgagattct ctgggaacct tggtggtggt 2160 gaagagtctt ctactgtcgg tgatttagct atcgtaggag gaggtgcttt gctttctact 2220 aatgaagtta atgtttgcag taaccaaaat gttgtttttt ctgataacgt gacttcaaat 2280 ggttgtgatt cagggggagc tattttagct aaaaaagtag atatctccgc gaaccactcg 2340 gttgaatttg tctctaatgg ttcagggaaa ttcggtggtg ccgtttgcgc tttaaacgaa 2400 tcagtaaaca ttacggacaa tggctcggca gtatcattct ctaaaaatag aacacgtctt 2460 ggcggtgctg gagttgcagc tcctcaaggc tctgtaacga tttgtggaaa tcagggaaac 2520 atagcattta aagagaactt tgtttttggc tctgaaaatc aaagatcagg tggaggagct 2580 atcattgcta actcttctgt aaatattcag gataacgcag gagatatcct atttgtaagt 2640 aactctacgg gatcttatgg aggtgctatt tttgtaggat ctttggttgc ttctgaaggc 2700 agcaacccac gaacgcttac aattacaggc aacagtgggg atatcctatt tgctaaaaat 2760 agcacgcaaa cagccgcttc tttatcagaa aaagattcct ttggtggagg ggccatctat 2820 acacaaaacc tcaaaattgt aaagaatgca gggaacgttt ctttctatgg caacagagct 2880 cctagtggtg ctggtgtcca aattgcagac ggaggaactg tttgtttaga ggcttttgga 2940 ggagatatct tatttgaagg gaatatcaat tttgatggga gtttcaatgc gattcactta 3000 tgcgggaatg actcaaaaat cgtagagctt tctgctgttc aagataaaaa tattattttc 3060 caagatgcaa ttacttatga agagaacaca attcgtggct tgccagataa agatgtcagt 3120 cctttaagtg ccccttcatt aatttttaac tccaagccac aagatgacag cgctcaacat 3180 catgaaggga cgatacggtt ttctcgaggg gtatctaaaa ttcctcagat tgctgctata 3240 caagagggaa ccttagcttt atcacaaaac gcagagcttt ggttggcagg acttaaacag 3300 gaaacaggaa gttctatcgt attgtctgcg ggatctattc tccgtatttt tgattcccag 3360 gttgatagca gtgcgcctct tcctacagaa aataaagagg agactcttgt ttctgccgga 3420 gttcaaatta acatgagctc tcctacaccc aataaagata aagctgtaga tactccagta 3480 cttgcagata tcataagtat tactgtagat ttgtcttcat ttgttcctga gcaagacgga 3540 actcttcctc ttcctcctga aattatcatt cctaagggaa caaaattaca ttctaatgcc 3600 atagatctta agattataga tcctaccaat gtgggatatg aaaatcatgc tcttctaagt 3660 tctcataaag atattccatt aatttctctt aagacagcgg aaggaatgac agggacgcct 3720 acagcagatg cttctctatc taatataaaa atagatgtat ctttaccttc gatcacacca 3780 gcaacgtatg gtcacacagg agtttggtct gaaagtaaaa tggaagatgg aagacttgta 3840 gtcggttggc aacctacggg atataagtta aatcctgaga agcaaggggc tctagttttg 3900 aataatctct ggagtcatta tacagatctt agagctctta agcaggagat ctttgctcat 3960 catacgatag ctcaaagaat ggagttagat ttctcgacaa atgtctgggg atcaggatta 4020 ggtgttgttg aagattgtca gaacatcgga gagtttgatg ggttcaaaca tcatctcaca 4080 gggtatgccc taggcttgga tacacaacta gttgaagact tcttaattgg aggatgtttc 4140 tcacagttct ttggtaaaac tgaaagccaa tcctacaaag ctaagaacga tgtgaagagt 4200 tatatgggag ctgcttatgc ggggatttta gcaggtcctt ggttaataaa aggagctttt 4260 gtttacggta atataaacaa cgatttgact acagattacg gtactttagg tatttcaaca 4320 ggttcatgga taggaaaagg gtttatcgca ggcacaagca ttgattaccg ctatattgta 4380 aatcctcgac ggtttatatc ggcaatcgta tccacagtgg ttccttttgt agaagccgag 4440 tatgtccgta tagatcttcc agaaattagc gaacagggta aagaggttag aacgttccaa 4500 aaaactcgtt ttgagaatgt cgccattcct tttggatttg ctttagaaca tgcttattcg 4560 cgtggctcac gtgctgaagt gaacagtgta cagcttgctt acgtctttga tgtatatcgt 4620 aagggacctg tctctttgat tacactcaag gatgctgctt attcttggaa gagttatggg 4680 gtagatattc cttgtaaagc ttggaaggct cgcttgagca ataatacgga atggaattca 4740 tatttaagta cgtatttagc gtttaattat gaatggagag aagatctgat agcttatgac 4800 ttcaatggtg gtatccgtat tattttctag 4830 60 591 DNA Chlamydia pneumoniae 60 atgacactct ccctagttgg aaaggaagcc cctgattttg ttgcgcaagc tgttgttaat 60 ggcgaaacgt gtaccgtatc tttaaaagat tatttaggaa agtatgttgt gcttttcttc 120 tatcctaaag attttactta cgtgtgtcct acggaattgc acgcatttca agatgcttta 180 ggagaattcc acacccgagg agctgaagtc ataggctgtt ccgtggatga cattgccacc 240 catcaacagt ggttagctac taagaaaaag caaggtggta tcgaaggtat tacctatcct 300 cttctctcag acgaagataa agtcatttca agaagttatc atgtgttaaa acccgaagaa 360 gaattatctt tcagaggagt tttcctgatt gataaaggtg gaatcatccg tcatcttgta 420 gtgaatgatc ttcctctagg ccgttctata gaagaagaac ttagaaccct agatgcttta 480 atcttctttg aaactaatgg cttagtctgt cctgcaaatt ggcatgaagg agagcgagcg 540 atggctccaa atgaagaagg actgcaaaat tatttcggga ctatagacta g 591 61 1983 DNA Chlamydia pneumoniae 61 atgagtgaac acaaaaaatc aagcaaaatt ataggtatag acttaggcac aacaaactcc 60 tgcgtatctg ttatggaagg aggacaagct aaagtaatta catcatccga aggaacaaga 120 accacgccat cgatcgttgc cttcaaaggt aatgagaaat tagtggggat tccagcaaaa 180 cgtcaagcag tgacaaatcc agaaaaaact ctcggctcta caaaacgctt tattggccgt 240 aagtactctg aagtagcttc ggaaatccaa accgttcctt atacagtcac ctccggatct 300 aaaggtgatg ccgttttcga agttgatggc aaacaataca ctccagaaga aattggcgca 360 caaatcttaa tgaaaatgaa agagacagca gaagcttatc taggcgaaac tgtcacagaa 420 gcagtgatca ccgtccccgc atacttcaat gattctcaac gagcatccac aaaagatgct 480 ggacgcattg caggtctaga tgtaaaacgt atcattccag aacctaccgc agcagctctt 540 gcctacggaa tcgataaagt cggtgataaa aaaatcgctg tcttcgacct tggtggagga 600 acttttgata tctccatcct agaaatcggt gatggcgtct tcgaagttct atctacaaat 660 ggagatactc tcctcggtgg agacgacttt gatgaagtca ttatcaaatg gatgatcgaa 720 gaattcaaaa aacaagaagg cattgatctt agcaaagata atatggcctt acaaagactt 780 aaagatgctg ctgagaaagc aaaaatagaa ctttcaggag tctcttccac agaaatcaat 840 cagccattca tcacaatgga tgcacaagga cctaaacacc ttgcattgac actcacacgt 900 gcgcaattcg agaaactcgc agcctctcta atcgaaagaa caaaatctcc atgcatcaaa 960 gcactcagtg acgcaaaact ttccgctaag gatatcgatg atgttctctt agttggaggt 1020 atgtcaagaa tgcccgcagt gcaagaaact gtaaaagaac tcttcggcaa agagcctaat 1080 aaaggagtca accccgacga agttgttgct attggagccg caattcaagg tggtgttctt 1140 ggcggagaag ttaaggatgt tctacttcta gacgttatcc ccctatctct gggtatcgaa 1200 actctaggag gcgtcatgac gactctggta gagagaaata ctacaatccc tacacagaaa 1260 aaacaaatct tctccacagc tgctgataac cagcctgcgg ttaccatcgt agttctccaa 1320 ggagagcgtc ccatggccaa agataacaag gaaatcggaa gattcgatct tacagatatc 1380 cctccggctc ctcgaggcca tcctcaaatc gaagtctcct tcgatatcga tgcaaacgga 1440 attttccatg tctcagctaa agatgttgcc agcggtaaag aacagaaaat tcgtatcgaa 1500 gcaagctcag gacttcaaga agatgaaatc caaagaatgg ttcgagatgc cgaaattaat 1560 aaggaagaag ataaaaaacg tcgtgaagct tcagatgcta aaaatgaagc cgatagcatg 1620 atcttcagag ccgaaaaagc tattaaagat tataaggagc aaattcctga aactttagtt 1680 aaagaaatcg aagagcgaat cgaaaacgtg cgcaacgcac tcaaagatga cgctcctatt 1740 gaaaaaatta aagaggttac tgaagaccta agcaagcata tgcaaaaaat tggagagtct 1800 atgcaatcgc agtctgcatc agcagcagca tcatcggcag ccaatgctaa aggtggacct 1860 aacatcaata cagaagattt gaaaaaacat agtttcagta cgaagcctcc ttcaaataac 1920 ggttcttcag aagaccatat cgaagaagct gatgtagaaa ttattgataa cgacgataag 1980 taa 1983 62 1860 DNA Chlamydia pneumoniae 62 atgaaaaaag ggaaattagg agccatagtt tttggccttc tatttacaag tagtgttgct 60 ggtttttcta aggatttgac taaagacaac gcttatcaag atttaaatgt catagagcat 120 ttaatatcgt taaaatatgc tcctttacca tggaaggaac tattatttgg ttgggattta 180 tctcagcaaa cacagcaagc tcgcttgcaa ctggtcttag aagaaaaacc aacaaccaac 240 tactgccaga aggtactctc taactacgtg agatcattaa acgattatca tgcagggatt 300 acgttttatc gtactgaaag tgcgtatatc ccttacgtat tgaagttaag tgaagatggt 360 catgtctttg tagtcgacgt acagactagc caaggggata tttacttagg ggatgaaatc 420 cttgaagtag atggaatggg gattcgtgag gctatcgaaa gccttcgctt tggacgaggg 480 agtgccacag actattctgc tgcagttcgt tccttgacat cgcgttccgc cgcttttgga 540 gatgcggttc cttcaggaat tgccatgttg aaacttcgcc gacccagtgg tttgatccgt 600 tcgacaccgg tccgttggcg ttatactcca gagcatatcg gagatttttc tttagttgct 660 cctttgattc ctgaacataa acctcaatta cctacacaaa gttgtgtgct attccgttcc 720 ggggtaaatt cacagtcttc tagtagctct ttattcagtt cctacatggt gccttatttc 780 tgggaagaat tgcgggttca aaataagcag cgttttgaca gtaatcacca tatagggagc 840 cgtaatggat ttttacctac gtttggtcct attctttggg aacaagacaa ggggccctat 900 cgttcctata tctttaaagc aaaagattct cagggcaatc cccatcgcat aggattttta 960 agaatttctt cttatgtttg gactgattta gaaggacttg aagaggatca taaggatagt 1020 ccttgggagc tctttggaga gatcatcgat catttggaaa aagagactga tgctttgatt 1080 attgatcaga cccataatcc tggaggcagt gttttctatc tctattcgtt actatctatg 1140 ttaacagatc atcctttaga tactcctaaa catagaatga ttttcactca ggatgaagtc 1200 agctcggctt tgcactggca agatctacta gaagatgtct tcacagatga gcaggcagtt 1260 gccgtgctag gggaaactat ggaaggatat tgcatggata tgcatgctgt agcctctctt 1320 caaaacttct ctcagagtgt cctttcttcc tgggtttcag gtgatattaa cctttcaaaa 1380 cctatgcctt tgctaggatt tgcacaggtt cgacctcatc ctaaacatca atatactaaa 1440 cctttgttta tgttgataga cgaggatgac ttctcttgtg gagatttagc gcctgcaatt 1500 ttgaaggata atggccgcgc tactctcatt ggaaagccaa cagcaggagc tggaggtttt 1560 gtattccaag tcactttccc taaccgttct ggaattaaag gtctttcttt aacaggatct 1620 ttagctgtta ggaaagatgg tgagtttatt gaaaacttag gagtggctcc tcatattgat 1680 ttaggattta cctccaggga tttgcaaact tccaggttta ctgattacgt tgaggcagtg 1740 aaaactatag ttttaacttc tttgtctgag aacgctaaga agagtgaaga gcagacttct 1800 ccgcaagaga cgcctgaagt tattcgagtc tcttatccca caacgacttc tgcttcgtaa 1860 63 1956 DNA Chlamydia pneumoniae 63 atggttaatc ctattggtcc aggtcctata gacgaaacag aacgcacacc tcccgcagat 60 ctttctgctc aaggattgga ggcgagtgca gcaaataaga gtgcggaagc tcaaagaata 120 gcaggtgcgg aagctaagcc taaagaatct aagaccgatt ctgtagagcg atggagcatc 180 ttgcgttctg cagtgaatgc tctcatgagt ctggcagata agctgggtat tgcttctagt 240 aacagctcgt cttctactag cagatctgca gacgtggact caacgacagc gaccgcacct 300 acgcctcctc cacccacgtt tgatgattat aagactcaag cgcaaacagc ttacgatact 360 atctttacct caacatcact agctgacata caggctgctt tggtgagcct ccaggatgct 420 gtcactaata taaaggatac agcggctact gatgaggaaa ccgcaatcgc tgcggagtgg 480 gaaactaaga atgccgatgc agttaaagtt ggcgcgcaaa ttacagaatt agcgaaatat 540 gcttcggata accaagcgat tcttgactct ttaggtaaac tgacttcctt cgacctctta 600 caggctgctc ttctccaatc tgtagcaaac aataacaaag cagctgagct tcttaaagag 660 atgcaagata acccagtagt cccagggaaa acgcctgcaa ttgctcaatc tttagttgat 720 cagacagatg ctacagcgac acagatagag aaagatggaa atgcgattag ggatgcatat 780 tttgcaggac agaacgctag tggagctgta gaaaatgcta aatctaataa cagtataagc 840 aacatagatt cagctaaagc agcaatcgct actgctaaga cacaaatagc tgaagctcag 900 aaaaagttcc ccgactctcc aattcttcaa gaagcggaac aaatggtaat acaggctgag 960 aaagatctta aaaatatcaa acctgcagat ggttctgatg ttccaaatcc aggaactaca 1020 gttggaggct ccaagcaaca aggaagtagt attggtagta ttcgtgtttc catgctgtta 1080 gatgatgctg aaaatgagac cgcttccatt ttgatgtctg ggtttcgtca gatgattcac 1140 atgttcaata cggaaaatcc tgattctcaa gctgcccaac aggagctcgc agcacaagct 1200 agagcagcga aagccgctgg agatgacagt gctgctgcag cgctggcaga tgctcagaaa 1260 gctttagaag cggctctagg taaagctggg caacaacagg gcatactcaa tgctttagga 1320 cagatcgctt ctgctgctgt tgtgagcgca ggagttcctc ccgctgcagc aagttctata 1380 gggtcatctg taaaacagct ttacaagacc tcaaaatcta caggttctga ttataaaaca 1440 cagatatcag caggttatga tgcttacaaa tccatcaatg atgcctatgg tagggcacga 1500 aatgatgcga ctcgtgatgt gataaacaat gtaagtaccc ccgctctcac acgatccgtt 1560 cctagagcac gaacagaagc tcgaggacca gaaaaaacag atcaagccct cgctagggtg 1620 atttctggca atagcagaac tcttggagat gtctatagtc aagtttcggc actacaatct 1680 gtaatgcaga tcatccagtc gaatcctcaa gcgaataatg aggagatcag acaaaagctt 1740 acatcggcag tgacaaagcc tccacagttt ggctatcctt atgtgcaact ttctaatgac 1800 tctacacaga agttcatagc taaattagaa agtttgtttg ctgaaggatc taggacagca 1860 gctgaaataa aagcactttc ctttgaaacg aactccttgt ttattcagca ggtgctggtc 1920 aatatcggct ctctatattc tggttatctc caataa 1956 64 264 DNA Chlamydia pneumoniae 64 atgagtcaaa aaaataaaaa ctctgctttt atgcatcccg tgaatatttc cacagattta 60 gcagttatag ttggcaaggg acctatgccc agaaccgaaa ttgtaaagaa agtttgggaa 120 tacattaaaa aacacaactg tcaggatcaa aaaaataaac gtaatatcct tcccgatgcg 180 aatcttgcca aagtctttgg ctctagtgat cctatcgaca tgttccaaat gaccaaagcc 240 ctttccaaac atattgtaaa ataa 264 65 978 PRT Chlamydia pneumoniae 65 Met Pro Leu Ser Phe Lys Ser Ser Ser Phe Cys Leu Leu Ala Cys Leu 5 10 15 Cys Ser Ala Ser Cys Ala Phe Ala Glu Thr Arg Leu Gly Gly Asn Phe 20 25 30 Val Pro Pro Ile Thr Asn Gln Gly Glu Glu Ile Leu Leu Thr Ser Asp 35 40 45 Phe Val Cys Ser Asn Phe Leu Gly Ala Ser Phe Ser Ser Ser Phe Ile 50 55 60 Asn Ser Ser Ser Asn Leu Ser Leu Leu Gly Lys Gly Leu Ser Leu Thr 65 70 75 80 Phe Thr Ser Cys Gln Ala Pro Thr Asn Ser Asn Tyr Ala Leu Leu Ser 85 90 95 Ala Ala Glu Thr Leu Thr Phe Lys Asn Phe Ser Ser Ile Asn Phe Thr 100 105 110 Gly Asn Gln Ser Thr Gly Leu Gly Gly Leu Ile Tyr Gly Lys Asp Ile 115 120 125 Val Phe Gln Ser Ile Lys Asp Leu Ile Phe Thr Thr Asn Arg Val Ala 130 135 140 Tyr Ser Pro Ala Ser Val Thr Thr Ser Ala Thr Pro Ala Ile Thr Thr 145 150 155 160 Val Thr Thr Gly Ala Ser Ala Leu Gln Pro Thr Asp Ser Leu Thr Val 165 170 175 Glu Asn Ile Ser Gln Ser Ile Lys Phe Phe Gly Asn Leu Ala Asn Phe 180 185 190 Gly Ser Ala Ile Ser Ser Ser Pro Thr Ala Val Val Lys Phe Ile Asn 195 200 205 Asn Thr Ala Thr Met Ser Phe Ser His Asn Phe Thr Ser Ser Gly Gly 210 215 220 Gly Val Ile Tyr Gly Gly Ser Ser Leu Leu Phe Glu Asn Asn Ser Gly 225 230 235 240 Cys Ile Ile Phe Thr Ala Asn Ser Cys Val Asn Ser Leu Lys Gly Val 245 250 255 Thr Pro Ser Ser Gly Thr Tyr Ala Leu Gly Ser Gly Gly Ala Ile Cys 260 265 270 Ile Pro Thr Gly Thr Phe Glu Leu Lys Asn Asn Gln Gly Lys Cys Thr 275 280 285 Phe Ser Tyr Asn Gly Thr Pro Asn Asp Ala Gly Ala Ile Tyr Ala Glu 290 295 300 Thr Cys Asn Ile Val Gly Asn Gln Gly Ala Leu Leu Leu Asp Ser Asn 305 310 315 320 Thr Ala Ala Arg Asn Gly Gly Ala Ile Cys Ala Lys Val Leu Asn Ile 325 330 335 Gln Gly Arg Gly Pro Ile Glu Phe Ser Arg Asn Arg Ala Glu Lys Gly 340 345 350 Gly Ala Ile Phe Ile Gly Pro Ser Val Gly Asp Pro Ala Lys Gln Thr 355 360 365 Ser Thr Leu Thr Ile Leu Ala Ser Glu Gly Asp Ile Ala Phe Gln Gly 370 375 380 Asn Met Leu Asn Thr Lys Pro Gly Ile Arg Asn Ala Ile Thr Val Glu 385 390 395 400 Ala Gly Gly Glu Ile Val Ser Leu Ser Ala Gln Gly Gly Ser Arg Leu 405 410 415 Val Phe Tyr Asp Pro Ile Thr His Ser Leu Pro Thr Thr Ser Pro Ser 420 425 430 Asn Lys Asp Ile Thr Ile Asn Ala Asn Gly Ala Ser Gly Ser Val Val 435 440 445 Phe Thr Ser Lys Gly Leu Ser Ser Thr Glu Leu Leu Leu Pro Ala Asn 450 455 460 Thr Thr Thr Ile Leu Leu Gly Thr Val Lys Ile Ala Ser Gly Glu Leu 465 470 475 480 Lys Ile Thr Asp Asn Ala Val Val Asn Val Leu Gly Phe Ala Thr Gln 485 490 495 Gly Ser Gly Gln Leu Thr Leu Gly Ser Gly Gly Thr Leu Gly Leu Ala 500 505 510 Thr Pro Thr Gly Ala Pro Ala Ala Val Asp Phe Thr Ile Gly Lys Leu 515 520 525 Ala Phe Asp Pro Phe Ser Phe Leu Lys Arg Asp Phe Val Ser Ala Ser 530 535 540 Val Asn Ala Gly Thr Lys Asn Val Thr Leu Thr Gly Ala Leu Val Leu 545 550 555 560 Asp Glu His Asp Val Thr Asp Leu Tyr Asp Met Val Ser Leu Gln Ser 565 570 575 Pro Val Ala Ile Pro Ile Ala Val Phe Lys Gly Ala Thr Val Thr Lys 580 585 590 Thr Gly Phe Pro Asp Gly Glu Ile Ala Thr Pro Ser His Tyr Gly Tyr 595 600 605 Gln Gly Lys Trp Ser Tyr Thr Trp Ser Arg Pro Leu Leu Ile Pro Ala 610 615 620 Pro Asp Gly Gly Phe Pro Gly Gly Pro Ser Pro Ser Ala Asn Thr Leu 625 630 635 640 Tyr Ala Val Trp Asn Ser Asp Thr Leu Val Arg Ser Thr Tyr Ile Leu 645 650 655 Asp Pro Glu Arg Tyr Gly Glu Ile Val Ser Asn Ser Leu Trp Ile Ser 660 665 670 Phe Leu Gly Asn Gln Ala Phe Ser Asp Ile Leu Gln Asp Val Leu Leu 675 680 685 Ile Asp His Pro Gly Leu Ser Ile Thr Ala Lys Ala Leu Gly Ala Tyr 690 695 700 Val Glu His Thr Pro Arg Gln Gly His Glu Gly Phe Ser Gly Arg Tyr 705 710 715 720 Gly Gly Tyr Gln Ala Ala Leu Ser Met Asn Tyr Thr Asp His Thr Thr 725 730 735 Leu Gly Leu Ser Phe Gly Gln Leu Tyr Gly Lys Thr Asn Ala Asn Pro 740 745 750 Tyr Asp Ser Arg Cys Ser Glu Gln Met Tyr Leu Leu Ser Phe Phe Gly 755 760 765 Gln Phe Pro Ile Val Thr Gln Lys Ser Glu Ala Leu Ile Ser Trp Lys 770 775 780 Ala Ala Tyr Gly Tyr Ser Lys Asn His Leu Asn Thr Thr Tyr Leu Arg 785 790 795 800 Pro Asp Lys Ala Pro Lys Ser Gln Gly Gln Trp His Asn Asn Ser Tyr 805 810 815 Tyr Val Leu Ile Ser Ala Glu His Pro Phe Leu Asn Trp Cys Leu Leu 820 825 830 Thr Arg Pro Leu Ala Gln Ala Trp Asp Leu Ser Gly Phe Ile Ser Ala 835 840 845 Glu Phe Leu Gly Gly Trp Gln Ser Lys Phe Thr Glu Thr Gly Asp Leu 850 855 860 Gln Arg Ser Phe Ser Arg Gly Lys Gly Tyr Asn Val Ser Leu Pro Ile 865 870 875 880 Gly Cys Ser Ser Gln Trp Phe Thr Pro Phe Lys Lys Ala Pro Ser Thr 885 890 895 Leu Thr Ile Lys Leu Ala Tyr Lys Pro Asp Ile Tyr Arg Val Asn Pro 900 905 910 His Asn Ile Val Thr Val Val Ser Asn Gln Glu Ser Thr Ser Ile Ser 915 920 925 Gly Ala Asn Leu Arg Arg His Gly Leu Phe Val Gln Ile His Asp Val 930 935 940 Val Asp Leu Thr Glu Asp Thr Gln Ala Phe Leu Asn Tyr Thr Phe Asp 945 950 955 960 Gly Lys Asn Gly Phe Thr Asn His Arg Val Ser Thr Gly Leu Lys Ser 965 970 975 Thr Phe 66 266 PRT Chlamydia pneumoniae 66 Met His Ser Lys Phe Leu Ser Arg Arg Lys Lys Asn Ser Ser His Lys 5 10 15 Glu Glu Thr Ser Trp Asp Cys Ile Ala Ser Ser Tyr Asn Lys Ile Val 20 25 30 Gln Asp Lys Gly His Tyr Tyr His Arg Glu Thr Ile Leu Pro Gln Leu 35 40 45 Leu Pro Ser Leu Thr Leu Gly Ser Lys Ser Ser Val Leu Asp Ile Gly 50 55 60 Cys Gly Gln Gly Phe Leu Glu Arg Ala Leu Pro Lys Glu Cys Arg Tyr 65 70 75 80 Leu Gly Ile Asp Ile Ser Ser Arg Leu Ile Ala Leu Ala Lys Lys Met 85 90 95 Arg Ser Val Asn Ser His Gln Phe Lys Val Ala Asp Leu Ser Lys Arg 100 105 110 Leu Glu Phe Val Glu Pro Thr Leu Phe Ser His Ala Val Ala Ile Leu 115 120 125 Ser Leu Gln Asn Met Glu Phe Pro Gly Glu Ala Ile Arg Asn Thr Ala 130 135 140 Thr Leu Leu Glu Pro Leu Gly Gln Phe Phe Ile Val Leu Asn His Pro 145 150 155 160 Cys Phe Arg Ile Pro Arg Ala Ser Ser Trp His Tyr Asp Glu Asn Lys 165 170 175 Lys Ala Ile Ser Arg His Ile Asp Arg Tyr Leu Ser Pro Met Lys Ile 180 185 190 Pro Ile Met Ala His Pro Gly Gln Lys Asp Ser Pro Ser Thr Leu Ser 195 200 205 Phe His Phe Pro Leu Ser Tyr Trp Phe Lys Glu Leu Ser Ser His Gly 210 215 220 Phe Leu Val Ser Gly Leu Glu Glu Trp Thr Ser Ser Lys Thr Ser Thr 225 230 235 240 Gly Lys Arg Ala Lys Ala Glu Asn Leu Cys Arg Lys Glu Phe Pro Leu 245 250 255 Phe Leu Met Ile Ser Cys Ile Lys Ile Lys 260 265 67 83 PRT Chlamydia pneumoniae 67 Met Lys Gln Gln His Asn Arg Lys Ala Leu Ser Arg Lys Ile Gly Thr 5 10 15 Val Lys Lys Gln Ala Lys Phe Ala Gly Ser Phe Leu Asp Glu Ile Lys 20 25 30 Lys Ile Glu Trp Val Ser Lys His Asp Leu Lys Lys Tyr Ile Lys Val 35 40 45 Val Leu Ile Ser Ile Phe Gly Phe Gly Phe Ala Ile Tyr Phe Val Asp 50 55 60 Leu Val Leu Arg Lys Ser Ile Thr Cys Leu Asp Gly Ile Thr Thr Phe 65 70 75 80 Leu Phe Gly 68 394 PRT Chlamydia pneumoniae 68 Met Ser Lys Glu Thr Phe Gln Arg Asn Lys Pro His Ile Asn Ile Gly 5 10 15 Thr Ile Gly His Val Asp His Gly Lys Thr Thr Leu Thr Ala Ala Ile 20 25 30 Thr Arg Ala Leu Ser Gly Asp Gly Leu Ala Ser Phe Arg Asp Tyr Ser 35 40 45 Ser Ile Asp Asn Thr Pro Glu Glu Lys Ala Arg Gly Ile Thr Ile Asn 50 55 60 Ala Ser His Val Glu Tyr Glu Thr Pro Asn Arg His Tyr Ala His Val 65 70 75 80 Asp Cys Pro Gly His Ala Asp Tyr Val Lys Asn Met Ile Thr Gly Ala 85 90 95 Ala Gln Met Asp Gly Ala Ile Leu Val Val Ser Ala Thr Asp Gly Ala 100 105 110 Met Pro Gln Thr Lys Glu His Ile Leu Leu Ala Arg Gln Val Gly Val 115 120 125 Pro Tyr Ile Val Val Phe Leu Asn Lys Val Asp Met Ile Ser Gln Glu 130 135 140 Asp Ala Glu Leu Ile Asp Leu Val Glu Met Glu Leu Ser Glu Leu Leu 145 150 155 160 Glu Glu Lys Gly Tyr Lys Gly Cys Pro Ile Ile Arg Gly Ser Ala Leu 165 170 175 Lys Ala Leu Glu Gly Asp Ala Asn Tyr Ile Glu Lys Val Arg Glu Leu 180 185 190 Met Gln Ala Val Asp Asp Asn Ile Pro Thr Pro Glu Arg Glu Ile Asp 195 200 205 Lys Pro Phe Leu Met Pro Ile Glu Asp Val Phe Ser Ile Ser Gly Arg 210 215 220 Gly Thr Val Val Thr Gly Arg Ile Glu Arg Gly Ile Val Lys Val Ser 225 230 235 240 Asp Lys Val Gln Leu Val Gly Leu Gly Glu Thr Lys Glu Thr Ile Val 245 250 255 Thr Gly Val Glu Met Phe Arg Lys Glu Leu Pro Glu Gly Arg Ala Gly 260 265 270 Glu Asn Val Gly Leu Leu Leu Arg Gly Ile Gly Lys Asn Asp Val Glu 275 280 285 Arg Gly Met Val Val Cys Gln Pro Asn Ser Val Lys Pro His Thr Lys 290 295 300 Phe Lys Ser Ala Val Tyr Val Leu Gln Lys Glu Glu Gly Gly Arg His 305 310 315 320 Lys Pro Phe Phe Ser Gly Tyr Arg Pro Gln Phe Phe Phe Arg Thr Thr 325 330 335 Asp Val Thr Gly Val Val Thr Leu Pro Glu Gly Thr Glu Met Val Met 340 345 350 Pro Gly Asp Asn Val Glu Leu Asp Val Glu Leu Ile Gly Thr Val Ala 355 360 365 Leu Glu Glu Gly Met Arg Phe Ala Ile Arg Glu Gly Gly Arg Thr Ile 370 375 380 Gly Ala Gly Thr Ile Ser Lys Ile Asn Ala 385 390 69 476 PRT Chlamydia pneumoniae 69 Met Arg Ile Val Gln Val Ala Val Glu Phe Thr Pro Ile Val Lys Val 5 10 15 Gly Gly Leu Gly Asp Ala Val Ala Ser Leu Ser Lys Glu Leu Ala Lys 20 25 30 Gln Asn Asp Val Glu Val Leu Leu Pro His Tyr Pro Leu Ile Ser Lys 35 40 45 Phe Ser Ser Ser Gln Val Leu Ser Glu Arg Ser Phe Tyr Tyr Glu Phe 50 55 60 Leu Gly Lys Gln Gln Ala Ser Ala Ile Ser Tyr Ser Tyr Glu Gly Leu 65 70 75 80 Thr Leu Thr Ile Ile Thr Leu Asp Ser Gln Ile Glu Leu Phe Ser Thr 85 90 95 Thr Ser Val Tyr Ser Glu Asn Asn Val Val Arg Phe Ser Ala Phe Ala 100 105 110 Ala Ala Ala Ala Ala Tyr Leu Gln Glu Ala Asp Pro Ala Asp Ile Val 115 120 125 His Leu His Asp Trp His Val Gly Leu Leu Ala Gly Leu Leu Lys Asn 130 135 140 Pro Leu Asn Pro Val His Ser Lys Ile Val Phe Thr Ile His Asn Phe 145 150 155 160 Gly Tyr Arg Gly Tyr Cys Ser Thr Gln Leu Leu Ala Ala Ser Gln Ile 165 170 175 Asp Asp Phe His Leu Ser His Tyr Gln Leu Phe Arg Asp Pro Gln Thr 180 185 190 Ser Val Leu Met Lys Gly Ala Leu Tyr Cys Ser Asp Tyr Ile Thr Thr 195 200 205 Val Ser Leu Thr Tyr Val Gln Glu Ile Ile Asn Asp Tyr Ser Asp Tyr 210 215 220 Glu Leu His Asp Ala Ile Leu Ala Arg Asn Ser Val Phe Ser Gly Ile 225 230 235 240 Ile Asn Gly Ile Asp Glu Asp Val Trp Asn Pro Lys Thr Asp Pro Ala 245 250 255 Leu Ala Val Gln Tyr Asp Ala Ser Leu Leu Ser Glu Pro Asp Val Leu 260 265 270 Phe Thr Lys Lys Glu Glu Asn Arg Ala Val Leu Tyr Glu Lys Leu Gly 275 280 285 Ile Ser Ser Asp Tyr Phe Pro Leu Ile Cys Val Ile Ser Arg Ile Val 290 295 300 Glu Glu Lys Gly Pro Glu Phe Met Lys Glu Ile Ile Leu His Ala Met 305 310 315 320 Glu His Ser Tyr Ala Phe Ile Leu Ile Gly Thr Ser Gln Asn Glu Val 325 330 335 Leu Leu Asn Glu Phe Arg Asn Leu Gln Asp Cys Leu Ala Ser Ser Pro 340 345 350 Asn Ile Arg Leu Ile Leu Asp Phe Asn Asp Pro Leu Ala Arg Leu Thr 355 360 365 Tyr Ala Ala Ala Asp Met Ile Cys Ile Pro Ser His Arg Glu Ala Cys 370 375 380 Gly Leu Thr Gln Leu Ile Ala Met Arg Tyr Gly Thr Val Pro Leu Val 385 390 395 400 Arg Lys Thr Gly Gly Leu Ala Asp Thr Val Ile Pro Gly Val Asn Gly 405 410 415 Phe Thr Phe Phe Asp Thr Asn Asn Phe Asn Glu Phe Arg Ala Met Leu 420 425 430 Ser Asn Ala Val Thr Thr Tyr Arg Gln Glu Pro Asp Val Trp Leu Asn 435 440 445 Leu Ile Glu Ser Gly Met Leu Arg Ala Ser Gly Leu Asp Ala Met Ala 450 455 460 Lys His Tyr Val Asn Leu Tyr Gln Ser Leu Leu Ser 465 470 475 70 346 PRT Chlamydia pneumoniae 70 Met Glu Ala Asp Ile Leu Asp Gly Lys Leu Lys Arg Val Glu Val Ser 5 10 15 Lys Lys Gly Leu Val Asn Cys Asn Gln Val Asp Val Asn Gln Leu Val 20 25 30 Pro Ile Lys Tyr Lys Trp Ala Trp Glu His Tyr Leu Asn Gly Cys Ala 35 40 45 Asn Asn Trp Leu Pro Thr Glu Val Pro Met Ala Arg Asp Ile Glu Leu 50 55 60 Trp Lys Ser Asp Glu Leu Ser Glu Asp Glu Arg Arg Val Ile Leu Leu 65 70 75 80 Asn Leu Gly Phe Phe Ser Thr Ala Glu Ser Leu Val Gly Asn Asn Ile 85 90 95 Val Leu Ala Ile Phe Lys His Ile Thr Asn Pro Glu Ala Arg Gln Tyr 100 105 110 Leu Leu Arg Gln Ala Phe Glu Glu Ala Val His Thr His Thr Phe Leu 115 120 125 Tyr Ile Cys Glu Ser Leu Gly Leu Asp Glu Gly Glu Val Phe Asn Ala 130 135 140 Tyr Asn Glu Arg Ala Ser Ile Arg Ala Lys Asp Asp Phe Gln Met Thr 145 150 155 160 Leu Thr Val Asp Val Leu Asp Pro Asn Phe Ser Val Gln Ser Ser Glu 165 170 175 Gly Leu Gly Gln Phe Ile Lys Asn Leu Val Gly Tyr Tyr Ile Ile Met 180 185 190 Glu Gly Ile Phe Phe Tyr Ser Gly Phe Val Met Ile Leu Ser Phe His 195 200 205 Arg Gln Asn Lys Met Thr Gly Ile Gly Glu Gln Tyr Gln Tyr Ile Leu 210 215 220 Arg Asp Glu Thr Ile His Leu Asn Phe Gly Ile Asp Leu Ile Asn Gly 225 230 235 240 Ile Lys Glu Glu Asn Pro Glu Val Trp Thr Thr Glu Leu Gln Glu Glu 245 250 255 Ile Val Ala Leu Ile Glu Lys Ala Val Glu Leu Glu Ile Glu Tyr Ala 260 265 270 Lys Asp Cys Leu Pro Arg Gly Ile Leu Gly Leu Arg Ser Ser Met Phe 275 280 285 Ile Asp Tyr Val Arg His Ile Ala Asp Arg Arg Leu Glu Arg Ile Gly 290 295 300 Leu Lys Pro Ile Tyr His Ser Arg Asn Pro Phe Pro Trp Met Ser Glu 305 310 315 320 Thr Met Asp Leu Asn Lys Glu Lys Asn Phe Phe Glu Thr Arg Val Thr 325 330 335 Glu Tyr Gln Thr Ala Gly Asn Leu Ser Trp 340 345 71 1044 PRT Chlamydia pneumoniae 71 Met Val Glu Val Glu Glu Lys His Tyr Thr Ile Val Lys Arg Asn Gly 5 10 15 Met Phe Val Pro Phe Asn Gln Asp Arg Ile Phe Gln Ala Leu Glu Ala 20 25 30 Ala Phe Arg Asp Thr Arg Ser Leu Glu Thr Ser Ser Pro Leu Pro Lys 35 40 45 Asp Leu Glu Glu Ser Ile Ala Gln Ile Thr His Lys Val Val Lys Glu 50 55 60 Val Leu Ala Lys Ile Ser Glu Gly Gln Val Val Thr Val Glu Arg Ile 65 70 75 80 Gln Asp Leu Val Glu Ser Gln Leu Tyr Ile Ser Gly Leu Gln Asp Val 85 90 95 Ala Arg Asp Tyr Ile Val Tyr Arg Asp Gln Arg Lys Ala Glu Arg Gly 100 105 110 Asn Ser Ser Ser Ile Ile Ala Ile Ile Arg Arg Asp Gly Gly Ser Ala 115 120 125 Lys Phe Asn Pro Met Lys Ile Ser Ala Ala Leu Glu Lys Ala Phe Arg 130 135 140 Ala Thr Leu Gln Ile Asn Gly Met Thr Pro Pro Ala Thr Leu Ser Glu 145 150 155 160 Ile Asn Asp Leu Thr Leu Arg Ile Val Glu Asp Val Leu Ser Leu His 165 170 175 Gly Glu Glu Ala Ile Asn Leu Glu Glu Ile Gln Asp Ile Val Glu Lys 180 185 190 Gln Leu Met Val Ala Gly Tyr Tyr Asp Val Ala Lys Asn Tyr Ile Leu 195 200 205 Tyr Arg Glu Ala Arg Ala Arg Ala Arg Ala Asn Lys Asp Gln Asp Gly 210 215 220 Gln Glu Glu Phe Val Pro Gln Glu Glu Thr Tyr Val Val Gln Lys Glu 225 230 235 240 Asp Gly Thr Thr Tyr Leu Leu Arg Lys Thr Asp Leu Glu Lys Arg Phe 245 250 255 Ser Trp Ala Cys Lys Arg Phe Pro Lys Thr Thr Asp Ser Gln Leu Leu 260 265 270 Ala Asp Met Ala Phe Met Asn Leu Tyr Ser Gly Ile Lys Glu Asp Glu 275 280 285 Val Thr Thr Ala Cys Ile Met Ala Ala Arg Ala Asn Ile Glu Arg Glu 290 295 300 Pro Asp Tyr Ala Phe Ile Ala Ala Glu Leu Leu Thr Ser Ser Leu Tyr 305 310 315 320 Glu Glu Thr Leu Gly Cys Ser Ser Gln Asp Pro Asn Leu Ser Glu Ile 325 330 335 His Lys Lys His Phe Lys Glu Tyr Ile Leu Asn Gly Glu Glu Tyr Arg 340 345 350 Leu Asn Pro Gln Leu Lys Asp Tyr Asp Leu Asp Ala Leu Ser Glu Val 355 360 365 Leu Asp Leu Ser Arg Asp Gln Gln Phe Ser Tyr Met Gly Val Gln Asn 370 375 380 Leu Tyr Asp Arg Tyr Phe Asn Leu His Glu Gly Arg Arg Leu Glu Thr 385 390 395 400 Ala Gln Ile Phe Trp Met Arg Val Ser Met Gly Leu Ala Leu Asn Glu 405 410 415 Gly Glu Gln Lys Asn Phe Trp Ala Ile Thr Phe Tyr Asn Leu Leu Ser 420 425 430 Thr Phe Arg Tyr Thr Pro Ala Thr Pro Thr Leu Phe Asn Ser Gly Met 435 440 445 Arg His Ser Gln Leu Ser Ser Cys Tyr Leu Ser Thr Val Lys Asp Asp 450 455 460 Leu Ser His Ile Tyr Lys Val Ile Ser Asp Asn Ala Leu Leu Ser Lys 465 470 475 480 Trp Ala Gly Gly Ile Gly Asn Asp Trp Thr Asp Val Arg Ala Thr Gly 485 490 495 Ala Val Ile Lys Gly Thr Asn Gly Lys Ser Gln Gly Val Ile Pro Phe 500 505 510 Ile Lys Val Ala Asn Asp Thr Ala Ile Ala Val Asn Gln Gly Gly Lys 515 520 525 Arg Lys Gly Ala Met Cys Val Tyr Leu Glu Asn Trp His Leu Asp Tyr 530 535 540 Glu Asp Phe Leu Glu Leu Arg Lys Asn Thr Gly Asp Glu Arg Arg Arg 545 550 555 560 Thr His Asp Ile Asn Thr Ala Ser Trp Ile Pro Asp Leu Phe Phe Lys 565 570 575 Arg Leu Glu Lys Lys Gly Met Trp Thr Leu Phe Ser Pro Asp Asp Val 580 585 590 Pro Gly Leu His Glu Ala Tyr Gly Leu Glu Phe Glu Lys Leu Tyr Glu 595 600 605 Glu Tyr Glu Arg Lys Val Glu Ser Gly Glu Ile Arg Leu Tyr Lys Lys 610 615 620 Val Glu Ala Glu Val Leu Trp Arg Lys Met Leu Ser Met Leu Tyr Glu 625 630 635 640 Thr Gly His Pro Trp Ile Thr Phe Lys Asp Pro Ser Asn Ile Arg Ser 645 650 655 Asn Gln Asp His Val Gly Val Val Arg Cys Ser Asn Leu Cys Thr Glu 660 665 670 Ile Leu Leu Asn Cys Ser Glu Ser Glu Thr Ala Val Cys Asn Leu Gly 675 680 685 Ser Ile Asn Leu Val Glu His Ile Arg Asn Asp Lys Leu Asp Glu Glu 690 695 700 Lys Leu Lys Glu Thr Ile Ser Ile Ala Ile Arg Ile Leu Asp Asn Val 705 710 715 720 Ile Asp Leu Asn Phe Tyr Pro Thr Pro Glu Ala Lys Gln Ala Asn Leu 725 730 735 Thr His Arg Ala Val Gly Leu Gly Val Met Gly Phe Gln Asp Val Leu 740 745 750 Tyr Glu Leu Asn Ile Ser Tyr Ala Ser Gln Glu Ala Val Glu Phe Ser 755 760 765 Asp Glu Cys Ser Glu Ile Ile Ala Tyr Tyr Ala Ile Leu Ala Ser Ser 770 775 780 Leu Leu Ala Lys Glu Arg Gly Thr Tyr Ala Ser Tyr Ser Gly Ser Lys 785 790 795 800 Trp Asp Arg Gly Tyr Leu Pro Leu Asp Thr Ile Glu Leu Leu Lys Glu 805 810 815 Thr Arg Gly Glu His Asn Val Leu Val Asp Thr Ser Ser Lys Lys Asp 820 825 830 Trp Thr Pro Val Arg Asp Thr Ile Gln Lys Tyr Gly Met Arg Asn Ser 835 840 845 Gln Val Met Ala Ile Ala Pro Thr Ala Thr Ile Ser Asn Ile Ile Gly 850 855 860 Val Thr Gln Ser Ile Glu Pro Met Tyr Lys His Leu Phe Val Lys Ser 865 870 875 880 Asn Leu Ser Gly Glu Phe Thr Ile Pro Asn Thr Tyr Leu Ile Lys Lys 885 890 895 Leu Lys Glu Leu Gly Leu Trp Asp Ala Glu Met Leu Asp Asp Leu Lys 900 905 910 Tyr Phe Asp Gly Ser Leu Leu Glu Ile Glu Arg Ile Pro Asn His Leu 915 920 925 Lys Lys Leu Phe Leu Thr Ala Phe Glu Ile Glu Pro Glu Trp Ile Ile 930 935 940 Glu Cys Thr Ser Arg Arg Gln Lys Trp Ile Asp Met Gly Val Ser Leu 945 950 955 960 Asn Leu Tyr Leu Ala Glu Pro Asp Gly Lys Lys Leu Ser Asn Met Tyr 965 970 975 Leu Thr Ala Trp Lys Lys Gly Leu Lys Thr Thr Tyr Tyr Leu Arg Ser 980 985 990 Gln Ala Ala Thr Ser Val Glu Lys Ser Phe Ile Asp Ile Asn Lys Arg 995 1000 1005 Gly Ile Gln Pro Arg Trp Met Lys Asn Lys Ser Ala Ser Thr Ser Ile 1010 1015 1020 Val Val Glu Arg Lys Thr Thr Pro Val Cys Ser Met Glu Glu Gly Cys 1025 1030 1035 1040 Glu Ser Cys Gln 72 461 PRT Chlamydia pneumoniae 72 Met Met Ser Ser Lys Arg Thr Ser Lys Ile Ala Val Leu Ser Ile Leu 5 10 15 Leu Thr Phe Thr His Ser Ile Gly Phe Ala Asn Ala Asn Ser Ser Val 20 25 30 Gly Leu Gly Thr Val Tyr Ile Thr Ser Glu Val Val Lys Lys Pro Gln 35 40 45 Lys Gly Ser Glu Arg Lys Gln Ala Lys Lys Glu Pro Arg Ala Arg Lys 50 55 60 Gly Tyr Leu Val Pro Ser Ser Arg Thr Leu Ser Ala Arg Ala Gln Lys 65 70 75 80 Met Lys Asn Ser Ser Arg Lys Glu Ser Ser Gly Gly Cys Asn Glu Ile 85 90 95 Ser Ala Asn Ser Thr Pro Arg Ser Val Lys Leu Arg Arg Asn Lys Arg 100 105 110 Ala Glu Gln Lys Ala Ala Lys Gln Gly Phe Ser Ala Phe Ser Asn Leu 115 120 125 Thr Leu Lys Ser Leu Leu Pro Lys Leu Pro Ser Lys Gln Lys Thr Ser 130 135 140 Ile His Glu Arg Glu Lys Ala Thr Ser Arg Phe Val Asn Glu Ser Gln 145 150 155 160 Leu Ser Ser Ala Arg Lys Arg Tyr Cys Thr Pro Ser Ser Ala Ala Pro 165 170 175 Ser Leu Phe Leu Glu Thr Glu Ile Val Arg Ala Pro Val Glu Arg Thr 180 185 190 Lys Glu Leu Gln Asp Asn Glu Ile His Ile Pro Val Val Gln Val Gln 195 200 205 Thr Asn Pro Lys Glu Gln Asn Thr Lys Thr Thr Lys Gln Leu Ala Ser 210 215 220 Gln Ala Ser Ile Gln Gln Ser Glu Gly Thr Glu Gln Ser Leu Arg Glu 225 230 235 240 Leu Ala Gln Gly Ala Ser Leu Pro Val Leu Val Arg Ser Asn Pro Glu 245 250 255 Val Ser Val Gln Arg Gln Lys Glu Glu Leu Leu Lys Glu Leu Val Ala 260 265 270 Glu Arg Arg Gln Cys Lys Arg Lys Ser Val Arg Gln Ala Leu Glu Ala 275 280 285 Arg Ser Leu Thr Lys Lys Val Ala Arg Gly Gly Ser Val Thr Ser Thr 290 295 300 Leu Arg Tyr Asp Pro Glu Lys Ala Ala Glu Ile Lys Ser Arg Arg Asn 305 310 315 320 Cys Lys Val Ser Pro Glu Ala Arg Glu Gln Lys Tyr Ser Ser Cys Lys 325 330 335 Arg Asp Ala Arg Ala Asn Gly Lys Gln Asp Lys Thr Thr Pro Ser Glu 340 345 350 Asp Ala Ser Gln Glu Glu Gln Gln Thr Gly Ala Gly Leu Val Arg Lys 355 360 365 Thr Pro Lys Ser Gln Val Ala Ser Asn Ala Gln Asn Phe Tyr Arg Asn 370 375 380 Ser Lys Asn Thr Asn Ile Asp Ser Tyr Leu Thr Ala Asn Gln Tyr Ser 385 390 395 400 Cys Ser Ser Glu Glu Thr Asp Trp Pro Cys Ser Ser Cys Val Ser Lys 405 410 415 Arg Arg Thr His Asn Ser Ile Ser Val Cys Thr Met Val Val Thr Val 420 425 430 Ile Ala Met Ile Val Gly Ala Leu Ile Ile Ala Asn Ala Thr Glu Ser 435 440 445 Gln Thr Thr Ser Asp Pro Thr Pro Pro Thr Pro Thr Pro 450 455 460 73 576 PRT Chlamydia pneumoniae 73 Met Thr Asp Phe Pro Thr His Phe Lys Gly Pro Lys Leu Asn Pro Ile 5 10 15 Lys Val Asn Pro Asn Phe Phe Glu Arg Asn Pro Lys Val Ala Arg Val 20 25 30 Leu Gln Ile Thr Ala Val Val Leu Gly Ile Ile Ala Leu Leu Ser Gly 35 40 45 Ile Val Leu Ile Ile Gly Thr Pro Leu Gly Ala Pro Ile Ser Met Ile 50 55 60 Leu Gly Gly Cys Leu Leu Ala Ser Gly Gly Ala Leu Phe Val Gly Gly 65 70 75 80 Thr Ile Ala Thr Ile Leu Gln Ala Arg Asn Ser Tyr Lys Lys Ala Val 85 90 95 Asn Gln Lys Lys Leu Ser Glu Pro Leu Met Glu Arg Pro Glu Leu Lys 100 105 110 Ala Leu Asp Tyr Ser Leu Asp Leu Lys Glu Val Trp Asp Leu His His 115 120 125 Ser Val Val Lys His Leu Lys Lys Leu Asp Leu Asn Leu Ser Lys Thr 130 135 140 Gln Arg Glu Val Leu Asn Gln Ile Lys Ile Asp Asp Glu Gly Pro Ser 145 150 155 160 Leu Gly Glu Cys Ala Ala Met Ile Ser Glu Asn Tyr Asp Ala Cys Leu 165 170 175 Lys Met Leu Ala Tyr Arg Glu Glu Leu Leu Lys Glu Gln Thr Gln Tyr 180 185 190 Gln Glu Thr Arg Phe Asn Gln Asn Leu Thr His Arg Asn Lys Val Leu 195 200 205 Leu Ser Ile Leu Ser Arg Ile Thr Asp Asn Ile Ser Lys Ala Gly Gly 210 215 220 Val Phe Ser Leu Lys Phe Ser Thr Leu Ser Ser Arg Met Ser Arg Ile 225 230 235 240 His Thr Thr Thr Thr Val Ile Leu Ala Leu Ser Ala Val Val Ser Val 245 250 255 Met Val Val Ala Ala Leu Ile Pro Gly Gly Ile Leu Ala Leu Pro Ile 260 265 270 Leu Leu Ala Val Ala Ile Ser Ala Gly Val Ile Val Thr Gly Leu Ser 275 280 285 Tyr Leu Val Arg Gln Ile Leu Ser Asn Thr Lys Arg Asn Arg Gln Asp 290 295 300 Phe Tyr Lys Asp Phe Val Lys Asn Val Asp Ile Glu Leu Leu Asn Gln 305 310 315 320 Thr Val Thr Leu Gln Arg Phe Leu Phe Glu Met Leu Lys Gly Val Leu 325 330 335 Lys Glu Glu Glu Glu Val Ser Leu Glu Gly Gln Asp Trp Tyr Thr Gln 340 345 350 Tyr Ile Thr Asn Ala Pro Ile Glu Lys Arg Leu Ile Glu Glu Ile Arg 355 360 365 Val Thr Tyr Lys Glu Ile Asp Ala Gln Thr Lys Lys Met Lys Thr Asp 370 375 380 Leu Glu Phe Leu Glu Asn Glu Val Arg Ser Gly Arg Leu Ser Val Ala 385 390 395 400 Ser Pro Ser Glu Asp Pro Ser Glu Thr Pro Ile Phe Thr Gln Gly Lys 405 410 415 Glu Phe Ala Lys Leu Arg Arg Gln Thr Ser Gln Asn Ile Ser Thr Ile 420 425 430 Tyr Gly Pro Asp Asn Glu Asn Ile Asp Pro Glu Phe Ser Leu Pro Trp 435 440 445 Met Pro Lys Lys Glu Glu Glu Ile Asp His Ser Leu Glu Pro Val Thr 450 455 460 Lys Leu Glu Pro Gly Ser Arg Glu Glu Leu Leu Leu Val Glu Gly Val 465 470 475 480 Asn Pro Thr Leu Arg Glu Leu Asn Met Arg Ile Ala Leu Leu Gln Gln 485 490 495 Gln Leu Ser Ser Val Arg Lys Trp Arg His Pro Arg Gly Glu His Tyr 500 505 510 Gly Asn Val Ile Tyr Ser Asp Thr Glu Leu Asp Arg Ile Gln Met Leu 515 520 525 Glu Gly Ala Phe Tyr Asn His Leu Arg Glu Ala Gln Glu Glu Ile Thr 530 535 540 Gln Ser Leu Gly Asp Leu Val Asp Ile Gln Asn Arg Ile Leu Gly Ile 545 550 555 560 Ile Val Glu Gly Asp Ser Asp Ser Arg Thr Glu Glu Glu Pro Gln Glu 565 570 575 74 361 PRT Chlamydia pneumoniae 74 Met Gln Gln Thr Val Ile Val Ala Met Ser Gly Gly Val Asp Ser Ser 5 10 15 Val Val Ala Tyr Leu Phe Lys Lys Phe Thr Asn Tyr Lys Val Ile Gly 20 25 30 Leu Phe Met Lys Asn Trp Glu Glu Asp Ser Glu Gly Gly Leu Cys Ser 35 40 45 Ser Thr Lys Asp Tyr Glu Asp Val Glu Arg Val Cys Leu Gln Leu Asp 50 55 60 Ile Pro Tyr Tyr Thr Val Ser Phe Ala Lys Glu Tyr Arg Glu Arg Val 65 70 75 80 Phe Ala Arg Phe Leu Lys Glu Tyr Ser Leu Gly Tyr Thr Pro Asn Pro 85 90 95 Asp Ile Leu Cys Asn Arg Glu Ile Lys Phe Asp Leu Leu Gln Lys Lys 100 105 110 Val Gln Glu Leu Gly Gly Asp Tyr Leu Ala Thr Gly His Tyr Cys Arg 115 120 125 Leu Asn Thr Glu Leu Gln Glu Thr Gln Leu Leu Arg Gly Cys Asp Pro 130 135 140 Gln Lys Asp Gln Ser Tyr Phe Leu Ser Gly Thr Pro Lys Ser Ala Leu 145 150 155 160 His Asn Val Leu Phe Pro Leu Gly Glu Met Asn Lys Thr Glu Val Arg 165 170 175 Ala Ile Ala Ala Gln Ala Ala Leu Pro Thr Ala Glu Lys Lys Asp Ser 180 185 190 Thr Gly Ile Cys Phe Ile Gly Lys Arg Pro Phe Lys Glu Phe Leu Glu 195 200 205 Lys Phe Leu Pro Asn Lys Thr Gly Asn Val Ile Asp Trp Asp Thr Lys 210 215 220 Glu Ile Val Gly Gln His Gln Gly Ala His Tyr Tyr Thr Ile Gly Gln 225 230 235 240 Arg Arg Gly Leu Asp Leu Gly Gly Ser Glu Lys Pro Cys Tyr Val Val 245 250 255 Gly Lys Asn Ile Glu Glu Asn Ser Ile Tyr Ile Val Arg Gly Glu Asp 260 265 270 His Pro Gln Leu Tyr Leu Arg Glu Leu Thr Ala Arg Glu Leu Asn Trp 275 280 285 Phe Thr Pro Pro Lys Ser Gly Cys His Cys Ser Ala Lys Val Arg Tyr 290 295 300 Arg Ser Pro Asp Glu Ala Cys Thr Ile Asp Tyr Ser Ser Gly Asp Glu 305 310 315 320 Val Lys Val Arg Phe Ser Gln Pro Val Lys Ala Val Thr Pro Gly Gln 325 330 335 Thr Ile Ala Phe Tyr Gln Gly Asp Thr Cys Leu Gly Ser Gly Val Ile 340 345 350 Asp Val Pro Met Ile Pro Ser Glu Gly 355 360 75 1609 PRT Chlamydia pneumoniae 75 Met Val Ala Lys Lys Thr Val Arg Ser Tyr Arg Ser Ser Phe Ser His 5 10 15 Ser Val Ile Val Ala Ile Leu Ser Ala Gly Ile Ala Phe Glu Ala His 20 25 30 Ser Leu His Ser Ser Glu Leu Asp Leu Gly Val Phe Asn Lys Gln Phe 35 40 45 Glu Glu His Ser Ala His Val Glu Glu Ala Gln Thr Ser Val Leu Lys 50 55 60 Gly Ser Asp Pro Val Asn Pro Ser Gln Lys Glu Ser Glu Lys Val Leu 65 70 75 80 Tyr Thr Gln Val Pro Leu Thr Gln Gly Ser Ser Gly Glu Ser Leu Asp 85 90 95 Leu Ala Asp Ala Asn Phe Leu Glu His Phe Gln His Leu Phe Glu Glu 100 105 110 Thr Thr Val Phe Gly Ile Asp Gln Lys Leu Val Trp Ser Asp Leu Asp 115 120 125 Thr Arg Asn Phe Ser Gln Pro Thr Gln Glu Pro Asp Thr Ser Asn Ala 130 135 140 Val Ser Glu Lys Ile Ser Ser Asp Thr Lys Glu Asn Arg Lys Asp Leu 145 150 155 160 Glu Thr Glu Asp Pro Ser Lys Lys Ser Gly Leu Lys Glu Val Ser Ser 165 170 175 Asp Leu Pro Lys Ser Pro Glu Thr Ala Val Ala Ala Ile Ser Glu Asp 180 185 190 Leu Glu Ile Ser Glu Asn Ile Ser Ala Arg Asp Pro Leu Gln Gly Leu 195 200 205 Ala Phe Phe Tyr Lys Asn Thr Ser Ser Gln Ser Ile Ser Glu Lys Asp 210 215 220 Ser Ser Phe Gln Gly Ile Ile Phe Ser Gly Ser Gly Ala Asn Ser Gly 225 230 235 240 Leu Gly Phe Glu Asn Leu Lys Ala Pro Lys Ser Gly Ala Ala Val Tyr 245 250 255 Ser Asp Arg Asp Ile Val Phe Glu Asn Leu Val Lys Gly Leu Ser Phe 260 265 270 Ile Ser Cys Glu Ser Leu Glu Asp Gly Ser Ala Ala Gly Val Asn Ile 275 280 285 Val Val Thr His Cys Gly Asp Val Thr Leu Thr Asp Cys Ala Thr Gly 290 295 300 Leu Asp Leu Glu Ala Leu Arg Leu Val Lys Asp Phe Ser Arg Gly Gly 305 310 315 320 Ala Val Phe Thr Ala Arg Asn His Glu Val Gln Asn Asn Leu Ala Gly 325 330 335 Gly Ile Leu Ser Val Val Gly Asn Lys Gly Ala Ile Val Val Glu Lys 340 345 350 Asn Ser Ala Glu Lys Ser Asn Gly Gly Ala Phe Ala Cys Gly Ser Phe 355 360 365 Val Tyr Ser Asn Asn Glu Asn Thr Ala Leu Trp Lys Glu Asn Gln Ala 370 375 380 Leu Ser Gly Gly Ala Ile Ser Ser Ala Ser Asp Ile Asp Ile Gln Gly 385 390 395 400 Asn Cys Ser Ala Ile Glu Phe Ser Gly Asn Gln Ser Leu Ile Ala Leu 405 410 415 Gly Glu His Ile Gly Leu Thr Asp Phe Val Gly Gly Gly Ala Leu Ala 420 425 430 Ala Gln Gly Thr Leu Thr Leu Arg Asn Asn Ala Val Val Gln Cys Val 435 440 445 Lys Asn Thr Ser Lys Thr His Gly Gly Ala Ile Leu Ala Gly Thr Val 450 455 460 Asp Leu Asn Glu Thr Ile Ser Glu Val Ala Phe Lys Gln Asn Thr Ala 465 470 475 480 Ala Leu Thr Gly Gly Ala Leu Ser Ala Asn Asp Lys Val Ile Ile Ala 485 490 495 Asn Asn Phe Gly Glu Ile Leu Phe Glu Gln Asn Glu Val Arg Asn His 500 505 510 Gly Gly Ala Ile Tyr Cys Gly Cys Arg Ser Asn Pro Lys Leu Glu Gln 515 520 525 Lys Asp Ser Gly Glu Asn Ile Asn Ile Ile Gly Asn Ser Gly Ala Ile 530 535 540 Thr Phe Leu Lys Asn Lys Ala Ser Val Leu Glu Val Met Thr Gln Ala 545 550 555 560 Glu Asp Tyr Ala Gly Gly Gly Ala Leu Trp Gly His Asn Val Leu Leu 565 570 575 Asp Ser Asn Ser Gly Asn Ile Gln Phe Ile Gly Asn Ile Gly Gly Ser 580 585 590 Thr Phe Trp Ile Gly Glu Tyr Val Gly Gly Gly Ala Ile Leu Ser Thr 595 600 605 Asp Arg Val Thr Ile Ser Asn Asn Ser Gly Asp Val Val Phe Lys Gly 610 615 620 Asn Lys Gly Gln Cys Leu Ala Gln Lys Tyr Val Ala Pro Gln Glu Thr 625 630 635 640 Ala Pro Val Glu Ser Asp Ala Ser Ser Thr Asn Lys Asp Glu Lys Ser 645 650 655 Leu Asn Ala Cys Ser His Gly Asp His Tyr Pro Pro Lys Thr Val Glu 660 665 670 Glu Glu Val Pro Pro Ser Leu Leu Glu Glu His Pro Val Val Ser Ser 675 680 685 Thr Asp Ile Arg Gly Gly Gly Ala Ile Leu Ala Gln His Ile Phe Ile 690 695 700 Thr Asp Asn Thr Gly Asn Leu Arg Phe Ser Gly Asn Leu Gly Gly Gly 705 710 715 720 Glu Glu Ser Ser Thr Val Gly Asp Leu Ala Ile Val Gly Gly Gly Ala 725 730 735 Leu Leu Ser Thr Asn Glu Val Asn Val Cys Ser Asn Gln Asn Val Val 740 745 750 Phe Ser Asp Asn Val Thr Ser Asn Gly Cys Asp Ser Gly Gly Ala Ile 755 760 765 Leu Ala Lys Lys Val Asp Ile Ser Ala Asn His Ser Val Glu Phe Val 770 775 780 Ser Asn Gly Ser Gly Lys Phe Gly Gly Ala Val Cys Ala Leu Asn Glu 785 790 795 800 Ser Val Asn Ile Thr Asp Asn Gly Ser Ala Val Ser Phe Ser Lys Asn 805 810 815 Arg Thr Arg Leu Gly Gly Ala Gly Val Ala Ala Pro Gln Gly Ser Val 820 825 830 Thr Ile Cys Gly Asn Gln Gly Asn Ile Ala Phe Lys Glu Asn Phe Val 835 840 845 Phe Gly Ser Glu Asn Gln Arg Ser Gly Gly Gly Ala Ile Ile Ala Asn 850 855 860 Ser Ser Val Asn Ile Gln Asp Asn Ala Gly Asp Ile Leu Phe Val Ser 865 870 875 880 Asn Ser Thr Gly Ser Tyr Gly Gly Ala Ile Phe Val Gly Ser Leu Val 885 890 895 Ala Ser Glu Gly Ser Asn Pro Arg Thr Leu Thr Ile Thr Gly Asn Ser 900 905 910 Gly Asp Ile Leu Phe Ala Lys Asn Ser Thr Gln Thr Ala Ala Ser Leu 915 920 925 Ser Glu Lys Asp Ser Phe Gly Gly Gly Ala Ile Tyr Thr Gln Asn Leu 930 935 940 Lys Ile Val Lys Asn Ala Gly Asn Val Ser Phe Tyr Gly Asn Arg Ala 945 950 955 960 Pro Ser Gly Ala Gly Val Gln Ile Ala Asp Gly Gly Thr Val Cys Leu 965 970 975 Glu Ala Phe Gly Gly Asp Ile Leu Phe Glu Gly Asn Ile Asn Phe Asp 980 985 990 Gly Ser Phe Asn Ala Ile His Leu Cys Gly Asn Asp Ser Lys Ile Val 995 1000 1005 Glu Leu Ser Ala Val Gln Asp Lys Asn Ile Ile Phe Gln Asp Ala Ile 1010 1015 1020 Thr Tyr Glu Glu Asn Thr Ile Arg Gly Leu Pro Asp Lys Asp Val Ser 1025 1030 1035 1040 Pro Leu Ser Ala Pro Ser Leu Ile Phe Asn Ser Lys Pro Gln Asp Asp 1045 1050 1055 Ser Ala Gln His His Glu Gly Thr Ile Arg Phe Ser Arg Gly Val Ser 1060 1065 1070 Lys Ile Pro Gln Ile Ala Ala Ile Gln Glu Gly Thr Leu Ala Leu Ser 1075 1080 1085 Gln Asn Ala Glu Leu Trp Leu Ala Gly Leu Lys Gln Glu Thr Gly Ser 1090 1095 1100 Ser Ile Val Leu Ser Ala Gly Ser Ile Leu Arg Ile Phe Asp Ser Gln 1105 1110 1115 1120 Val Asp Ser Ser Ala Pro Leu Pro Thr Glu Asn Lys Glu Glu Thr Leu 1125 1130 1135 Val Ser Ala Gly Val Gln Ile Asn Met Ser Ser Pro Thr Pro Asn Lys 1140 1145 1150 Asp Lys Ala Val Asp Thr Pro Val Leu Ala Asp Ile Ile Ser Ile Thr 1155 1160 1165 Val Asp Leu Ser Ser Phe Val Pro Glu Gln Asp Gly Thr Leu Pro Leu 1170 1175 1180 Pro Pro Glu Ile Ile Ile Pro Lys Gly Thr Lys Leu His Ser Asn Ala 1185 1190 1195 1200 Ile Asp Leu Lys Ile Ile Asp Pro Thr Asn Val Gly Tyr Glu Asn His 1205 1210 1215 Ala Leu Leu Ser Ser His Lys Asp Ile Pro Leu Ile Ser Leu Lys Thr 1220 1225 1230 Ala Glu Gly Met Thr Gly Thr Pro Thr Ala Asp Ala Ser Leu Ser Asn 1235 1240 1245 Ile Lys Ile Asp Val Ser Leu Pro Ser Ile Thr Pro Ala Thr Tyr Gly 1250 1255 1260 His Thr Gly Val Trp Ser Glu Ser Lys Met Glu Asp Gly Arg Leu Val 1265 1270 1275 1280 Val Gly Trp Gln Pro Thr Gly Tyr Lys Leu Asn Pro Glu Lys Gln Gly 1285 1290 1295 Ala Leu Val Leu Asn Asn Leu Trp Ser His Tyr Thr Asp Leu Arg Ala 1300 1305 1310 Leu Lys Gln Glu Ile Phe Ala His His Thr Ile Ala Gln Arg Met Glu 1315 1320 1325 Leu Asp Phe Ser Thr Asn Val Trp Gly Ser Gly Leu Gly Val Val Glu 1330 1335 1340 Asp Cys Gln Asn Ile Gly Glu Phe Asp Gly Phe Lys His His Leu Thr 1345 1350 1355 1360 Gly Tyr Ala Leu Gly Leu Asp Thr Gln Leu Val Glu Asp Phe Leu Ile 1365 1370 1375 Gly Gly Cys Phe Ser Gln Phe Phe Gly Lys Thr Glu Ser Gln Ser Tyr 1380 1385 1390 Lys Ala Lys Asn Asp Val Lys Ser Tyr Met Gly Ala Ala Tyr Ala Gly 1395 1400 1405 Ile Leu Ala Gly Pro Trp Leu Ile Lys Gly Ala Phe Val Tyr Gly Asn 1410 1415 1420 Ile Asn Asn Asp Leu Thr Thr Asp Tyr Gly Thr Leu Gly Ile Ser Thr 1425 1430 1435 1440 Gly Ser Trp Ile Gly Lys Gly Phe Ile Ala Gly Thr Ser Ile Asp Tyr 1445 1450 1455 Arg Tyr Ile Val Asn Pro Arg Arg Phe Ile Ser Ala Ile Val Ser Thr 1460 1465 1470 Val Val Pro Phe Val Glu Ala Glu Tyr Val Arg Ile Asp Leu Pro Glu 1475 1480 1485 Ile Ser Glu Gln Gly Lys Glu Val Arg Thr Phe Gln Lys Thr Arg Phe 1490 1495 1500 Glu Asn Val Ala Ile Pro Phe Gly Phe Ala Leu Glu His Ala Tyr Ser 1505 1510 1515 1520 Arg Gly Ser Arg Ala Glu Val Asn Ser Val Gln Leu Ala Tyr Val Phe 1525 1530 1535 Asp Val Tyr Arg Lys Gly Pro Val Ser Leu Ile Thr Leu Lys Asp Ala 1540 1545 1550 Ala Tyr Ser Trp Lys Ser Tyr Gly Val Asp Ile Pro Cys Lys Ala Trp 1555 1560 1565 Lys Ala Arg Leu Ser Asn Asn Thr Glu Trp Asn Ser Tyr Leu Ser Thr 1570 1575 1580 Tyr Leu Ala Phe Asn Tyr Glu Trp Arg Glu Asp Leu Ile Ala Tyr Asp 1585 1590 1595 1600 Phe Asn Gly Gly Ile Arg Ile Ile Phe 1605 76 196 PRT Chlamydia pneumoniae 76 Met Thr Leu Ser Leu Val Gly Lys Glu Ala Pro Asp Phe Val Ala Gln 5 10 15 Ala Val Val Asn Gly Glu Thr Cys Thr Val Ser Leu Lys Asp Tyr Leu 20 25 30 Gly Lys Tyr Val Val Leu Phe Phe Tyr Pro Lys Asp Phe Thr Tyr Val 35 40 45 Cys Pro Thr Glu Leu His Ala Phe Gln Asp Ala Leu Gly Glu Phe His 50 55 60 Thr Arg Gly Ala Glu Val Ile Gly Cys Ser Val Asp Asp Ile Ala Thr 65 70 75 80 His Gln Gln Trp Leu Ala Thr Lys Lys Lys Gln Gly Gly Ile Glu Gly 85 90 95 Ile Thr Tyr Pro Leu Leu Ser Asp Glu Asp Lys Val Ile Ser Arg Ser 100 105 110 Tyr His Val Leu Lys Pro Glu Glu Glu Leu Ser Phe Arg Gly Val Phe 115 120 125 Leu Ile Asp Lys Gly Gly Ile Ile Arg His Leu Val Val Asn Asp Leu 130 135 140 Pro Leu Gly Arg Ser Ile Glu Glu Glu Leu Arg Thr Leu Asp Ala Leu 145 150 155 160 Ile Phe Phe Glu Thr Asn Gly Leu Val Cys Pro Ala Asn Trp His Glu 165 170 175 Gly Glu Arg Ala Met Ala Pro Asn Glu Glu Gly Leu Gln Asn Tyr Phe 180 185 190 Gly Thr Ile Asp 195 77 619 PRT Chlamydia pneumoniae 77 Met Lys Lys Gly Lys Leu Gly Ala Ile Val Phe Gly Leu Leu Phe Thr 5 10 15 Ser Ser Val Ala Gly Phe Ser Lys Asp Leu Thr Lys Asp Asn Ala Tyr 20 25 30 Gln Asp Leu Asn Val Ile Glu His Leu Ile Ser Leu Lys Tyr Ala Pro 35 40 45 Leu Pro Trp Lys Glu Leu Leu Phe Gly Trp Asp Leu Ser Gln Gln Thr 50 55 60 Gln Gln Ala Arg Leu Gln Leu Val Leu Glu Glu Lys Pro Thr Thr Asn 65 70 75 80 Tyr Cys Gln Lys Val Leu Ser Asn Tyr Val Arg Ser Leu Asn Asp Tyr 85 90 95 His Ala Gly Ile Thr Phe Tyr Arg Thr Glu Ser Ala Tyr Ile Pro Tyr 100 105 110 Val Leu Lys Leu Ser Glu Asp Gly His Val Phe Val Val Asp Val Gln 115 120 125 Thr Ser Gln Gly Asp Ile Tyr Leu Gly Asp Glu Ile Leu Glu Val Asp 130 135 140 Gly Met Gly Ile Arg Glu Ala Ile Glu Ser Leu Arg Phe Gly Arg Gly 145 150 155 160 Ser Ala Thr Asp Tyr Ser Ala Ala Val Arg Ser Leu Thr Ser Arg Ser 165 170 175 Ala Ala Phe Gly Asp Ala Val Pro Ser Gly Ile Ala Met Leu Lys Leu 180 185 190 Arg Arg Pro Ser Gly Leu Ile Arg Ser Thr Pro Val Arg Trp Arg Tyr 195 200 205 Thr Pro Glu His Ile Gly Asp Phe Ser Leu Val Ala Pro Leu Ile Pro 210 215 220 Glu His Lys Pro Gln Leu Pro Thr Gln Ser Cys Val Leu Phe Arg Ser 225 230 235 240 Gly Val Asn Ser Gln Ser Ser Ser Ser Ser Leu Phe Ser Ser Tyr Met 245 250 255 Val Pro Tyr Phe Trp Glu Glu Leu Arg Val Gln Asn Lys Gln Arg Phe 260 265 270 Asp Ser Asn His His Ile Gly Ser Arg Asn Gly Phe Leu Pro Thr Phe 275 280 285 Gly Pro Ile Leu Trp Glu Gln Asp Lys Gly Pro Tyr Arg Ser Tyr Ile 290 295 300 Phe Lys Ala Lys Asp Ser Gln Gly Asn Pro His Arg Ile Gly Phe Leu 305 310 315 320 Arg Ile Ser Ser Tyr Val Trp Thr Asp Leu Glu Gly Leu Glu Glu Asp 325 330 335 His Lys Asp Ser Pro Trp Glu Leu Phe Gly Glu Ile Ile Asp His Leu 340 345 350 Glu Lys Glu Thr Asp Ala Leu Ile Ile Asp Gln Thr His Asn Pro Gly 355 360 365 Gly Ser Val Phe Tyr Leu Tyr Ser Leu Leu Ser Met Leu Thr Asp His 370 375 380 Pro Leu Asp Thr Pro Lys His Arg Met Ile Phe Thr Gln Asp Glu Val 385 390 395 400 Ser Ser Ala Leu His Trp Gln Asp Leu Leu Glu Asp Val Phe Thr Asp 405 410 415 Glu Gln Ala Val Ala Val Leu Gly Glu Thr Met Glu Gly Tyr Cys Met 420 425 430 Asp Met His Ala Val Ala Ser Leu Gln Asn Phe Ser Gln Ser Val Leu 435 440 445 Ser Ser Trp Val Ser Gly Asp Ile Asn Leu Ser Lys Pro Met Pro Leu 450 455 460 Leu Gly Phe Ala Gln Val Arg Pro His Pro Lys His Gln Tyr Thr Lys 465 470 475 480 Pro Leu Phe Met Leu Ile Asp Glu Asp Asp Phe Ser Cys Gly Asp Leu 485 490 495 Ala Pro Ala Ile Leu Lys Asp Asn Gly Arg Ala Thr Leu Ile Gly Lys 500 505 510 Pro Thr Ala Gly Ala Gly Gly Phe Val Phe Gln Val Thr Phe Pro Asn 515 520 525 Arg Ser Gly Ile Lys Gly Leu Ser Leu Thr Gly Ser Leu Ala Val Arg 530 535 540 Lys Asp Gly Glu Phe Ile Glu Asn Leu Gly Val Ala Pro His Ile Asp 545 550 555 560 Leu Gly Phe Thr Ser Arg Asp Leu Gln Thr Ser Arg Phe Thr Asp Tyr 565 570 575 Val Glu Ala Val Lys Thr Ile Val Leu Thr Ser Leu Ser Glu Asn Ala 580 585 590 Lys Lys Ser Glu Glu Gln Thr Ser Pro Gln Glu Thr Pro Glu Val Ile 595 600 605 Arg Val Ser Tyr Pro Thr Thr Thr Ser Ala Ser 610 615 78 651 PRT Chlamydia pneumoniae 78 Met Val Asn Pro Ile Gly Pro Gly Pro Ile Asp Glu Thr Glu Arg Thr 5 10 15 Pro Pro Ala Asp Leu Ser Ala Gln Gly Leu Glu Ala Ser Ala Ala Asn 20 25 30 Lys Ser Ala Glu Ala Gln Arg Ile Ala Gly Ala Glu Ala Lys Pro Lys 35 40 45 Glu Ser Lys Thr Asp Ser Val Glu Arg Trp Ser Ile Leu Arg Ser Ala 50 55 60 Val Asn Ala Leu Met Ser Leu Ala Asp Lys Leu Gly Ile Ala Ser Ser 65 70 75 80 Asn Ser Ser Ser Ser Thr Ser Arg Ser Ala Asp Val Asp Ser Thr Thr 85 90 95 Ala Thr Ala Pro Thr Pro Pro Pro Pro Thr Phe Asp Asp Tyr Lys Thr 100 105 110 Gln Ala Gln Thr Ala Tyr Asp Thr Ile Phe Thr Ser Thr Ser Leu Ala 115 120 125 Asp Ile Gln Ala Ala Leu Val Ser Leu Gln Asp Ala Val Thr Asn Ile 130 135 140 Lys Asp Thr Ala Ala Thr Asp Glu Glu Thr Ala Ile Ala Ala Glu Trp 145 150 155 160 Glu Thr Lys Asn Ala Asp Ala Val Lys Val Gly Ala Gln Ile Thr Glu 165 170 175 Leu Ala Lys Tyr Ala Ser Asp Asn Gln Ala Ile Leu Asp Ser Leu Gly 180 185 190 Lys Leu Thr Ser Phe Asp Leu Leu Gln Ala Ala Leu Leu Gln Ser Val 195 200 205 Ala Asn Asn Asn Lys Ala Ala Glu Leu Leu Lys Glu Met Gln Asp Asn 210 215 220 Pro Val Val Pro Gly Lys Thr Pro Ala Ile Ala Gln Ser Leu Val Asp 225 230 235 240 Gln Thr Asp Ala Thr Ala Thr Gln Ile Glu Lys Asp Gly Asn Ala Ile 245 250 255 Arg Asp Ala Tyr Phe Ala Gly Gln Asn Ala Ser Gly Ala Val Glu Asn 260 265 270 Ala Lys Ser Asn Asn Ser Ile Ser Asn Ile Asp Ser Ala Lys Ala Ala 275 280 285 Ile Ala Thr Ala Lys Thr Gln Ile Ala Glu Ala Gln Lys Lys Phe Pro 290 295 300 Asp Ser Pro Ile Leu Gln Glu Ala Glu Gln Met Val Ile Gln Ala Glu 305 310 315 320 Lys Asp Leu Lys Asn Ile Lys Pro Ala Asp Gly Ser Asp Val Pro Asn 325 330 335 Pro Gly Thr Thr Val Gly Gly Ser Lys Gln Gln Gly Ser Ser Ile Gly 340 345 350 Ser Ile Arg Val Ser Met Leu Leu Asp Asp Ala Glu Asn Glu Thr Ala 355 360 365 Ser Ile Leu Met Ser Gly Phe Arg Gln Met Ile His Met Phe Asn Thr 370 375 380 Glu Asn Pro Asp Ser Gln Ala Ala Gln Gln Glu Leu Ala Ala Gln Ala 385 390 395 400 Arg Ala Ala Lys Ala Ala Gly Asp Asp Ser Ala Ala Ala Ala Leu Ala 405 410 415 Asp Ala Gln Lys Ala Leu Glu Ala Ala Leu Gly Lys Ala Gly Gln Gln 420 425 430 Gln Gly Ile Leu Asn Ala Leu Gly Gln Ile Ala Ser Ala Ala Val Val 435 440 445 Ser Ala Gly Val Pro Pro Ala Ala Ala Ser Ser Ile Gly Ser Ser Val 450 455 460 Lys Gln Leu Tyr Lys Thr Ser Lys Ser Thr Gly Ser Asp Tyr Lys Thr 465 470 475 480 Gln Ile Ser Ala Gly Tyr Asp Ala Tyr Lys Ser Ile Asn Asp Ala Tyr 485 490 495 Gly Arg Ala Arg Asn Asp Ala Thr Arg Asp Val Ile Asn Asn Val Ser 500 505 510 Thr Pro Ala Leu Thr Arg Ser Val Pro Arg Ala Arg Thr Glu Ala Arg 515 520 525 Gly Pro Glu Lys Thr Asp Gln Ala Leu Ala Arg Val Ile Ser Gly Asn 530 535 540 Ser Arg Thr Leu Gly Asp Val Tyr Ser Gln Val Ser Ala Leu Gln Ser 545 550 555 560 Val Met Gln Ile Ile Gln Ser Asn Pro Gln Ala Asn Asn Glu Glu Ile 565 570 575 Arg Gln Lys Leu Thr Ser Ala Val Thr Lys Pro Pro Gln Phe Gly Tyr 580 585 590 Pro Tyr Val Gln Leu Ser Asn Asp Ser Thr Gln Lys Phe Ile Ala Lys 595 600 605 Leu Glu Ser Leu Phe Ala Glu Gly Ser Arg Thr Ala Ala Glu Ile Lys 610 615 620 Ala Leu Ser Phe Glu Thr Asn Ser Leu Phe Ile Gln Gln Val Leu Val 625 630 635 640 Asn Ile Gly Ser Leu Tyr Ser Gly Tyr Leu Gln 645 650 79 87 PRT Chlamydia pneumoniae 79 Met Ser Gln Lys Asn Lys Asn Ser Ala Phe Met His Pro Val Asn Ile 5 10 15 Ser Thr Asp Leu Ala Val Ile Val Gly Lys Gly Pro Met Pro Arg Thr 20 25 30 Glu Ile Val Lys Lys Val Trp Glu Tyr Ile Lys Lys His Asn Cys Gln 35 40 45 Asp Gln Lys Asn Lys Arg Asn Ile Leu Pro Asp Ala Asn Leu Ala Lys 50 55 60 Val Phe Gly Ser Ser Asp Pro Ile Asp Met Phe Gln Met Thr Lys Ala 65 70 75 80 Leu Ser Lys His Ile Val Lys 85 80 3048 DNA Chlamydia trachomatis serovar D 80 atgccttttt ctttgagatc tacatcattt tgttttttag cttgtttgtg ttcctattcg 60 tatggattcg cgagctctcc tcaagtgtta acacctaatg taaccactcc ttttaagggg 120 gacgatgttt acttgaatgg agactgcgct tttgtcaatg tctatgcagg ggcagagaac 180 ggctcaatta tctcagctaa tggcgacaat ttaacgatta ccggacaaaa ccatacatta 240 tcatttacag attctcaagg gccagttctt caaaattatg ccttcatttc agcaggagag 300 acacttactc tgaaagattt ttcgagtttg atgttctcga aaaatgtttc ttgcggagaa 360 aagggaatga tctcagggaa aaccgtgagt atttccggag caggcgaagt gattttttgg 420 gataactctg tggggtattc tcctttgtct attgtgccag catcgactcc aactcctcca 480 gcaccagcac cagctcctgc tgcttcaagc tctttatctc caacagttag tgatgctcgg 540 aaagggtcta ttttttctgt agagactagt ttggagatct caggcgtcaa aaaaggggtc 600 atgttcgata ataatgccgg gaattttgga acagtttttc gaggtaatag taataataat 660 gctggtagtg ggggtagtgg gtctgctaca acaccaagtt ttacagttaa aaactgtaaa 720 gggaaagttt ctttcacaga taacgtagcc tcctgtggag gcggagtagt ctacaaagga 780 actgtgcttt tcaaagacaa tgaaggaggc atattcttcc gagggaacac agcatacgat 840 gatttaggga ttcttgctgc tactagtcgg gatcagaata cggagacagg aggcggtgga 900 ggagttattt gctctccaga tgattctgta aagtttgaag gcaataaagg ttctattgtt 960 tttgattaca actttgcaaa aggcagaggc ggaagcatcc taacgaaaga attctctctt 1020 gtagcagatg attcggttgt ctttagtaac aatacagcag aaaaaggcgg tggagctatt 1080 tatgctccta ctatcgatat aagcacgaat ggaggatcga ttctatttga aagaaaccga 1140 gctgcagaag gaggcgccat ctgcgtgagt gaagcaagct ctggttcaac tggaaatctt 1200 actttaagcg cttctgatgg ggatattgtt ttttctggga atatgacgag tgatcgtcct 1260 ggagagcgca gcgcagcaag aatcttaagt gatggaacga ctgtttcttt aaatgcttcc 1320 ggactatcga agctgatctt ttatgatcct gtagtacaaa ataattcagc agcgggtgca 1380 tcgacaccat caccatcttc ttcttctatg cctggtgctg tcacgattaa tcagtccggt 1440 aatggatctg tgatttttac cgccgagtca ttgactcctt cagaaaaact tcaagttctt 1500 aactctactt ctaacttccc aggagctctg actgtgtcag gaggggagtt ggttgtgacg 1560 gaaggagcta ccttaactac tgggaccatt acagccacct ctggacgagt gactttagga 1620 tccggagctt cgttgtctgc cgttgcaggt gctgcaaata ataattatac ttgtacagta 1680 tctaagttgg ggattgattt agaatccttt ttaactccta actataagac ggccatactg 1740 ggtgcggatg gaacagttac tgttaacagc ggctctactt tagacctagt gatggagagt 1800 gaggcagagg tatatgataa tccgcttttt gtgggatcgc tgacaattcc ttttgttact 1860 ctatcttcta gtagtgctag taacggagtt acaaaaaatt ctgtcactat taatgatgca 1920 gacgctgcgc actatgggta tcaaggctct tggtctgcag attggacgaa accgcctctg 1980 gctcctgatg ctaaggggat ggtacctcct aataccaata acactctgta tctgacatgg 2040 agacctgctt cgaattacgg tgaatatcga ctggatcctc agagaaaggg agaactagta 2100 cccaactctc tttgggtagc gggatctgca ttaagaacct ttactaatgg tttgaaagaa 2160 cactatgttt ctagagatgt tggatttgta gcatctctgc atgctctcgg ggattatatt 2220 ttgaattata cgcaagatga tcgggatggc tttttagcta gatatggggg attccaggcg 2280 accgcagcct cccattatga aaatgggtca atatttggag tggcttttgg acaactctat 2340 ggtcagacaa agagcagaat gtattactct aaagatgctg ggaacatgac gatgttgtcc 2400 tgtttcggaa gaagttacgt agatattaaa ggaacagaaa ctgttatgta ttgggagacg 2460 gcttatggct attctgtgca cagaatgcat acgcagtatt ttaatgacaa aacgcagaag 2520 ttcgatcatt cgaaatgtca ttggcacaac aataactatt atgcgtttgt gggtgccgag 2580 cataatttct tagagtactg cattcctact cgtcagttcg ctagagatta tgagcttaca 2640 gggtttatgc gttttgaaat ggccggagga tggtccagtt ctacacgaga aactggctcc 2700 ctaactagat atttcgctcg cgggtcaggg cataatatgt cgcttccaat aggaattgta 2760 gctcatgcag tttctcatgt gcgaagatct cctccttcta aactgacact aaatatggga 2820 tatagaccag acatttggcg tgtcactcca cattgcaata tggaaattat tgctaacgga 2880 gtgaagacac ctatacaagg atctccgctg gcacggcatg ccttcttctt agaagtgcat 2940 gatactttgt atattcatca ttttggaaga gcctatatga actattcgct ggatgctcgt 3000 cgtcgacaaa cggcacattt tgtatccatg ggcttgaata gaatcttt 3048 81 1038 DNA Chlamydia trachomatis serovar D 81 atgcaagcag atattttaga tggaaaacag aaacgcgtta atctaaatag caagcgtcta 60 gtgaactgca accaggtcga tgtcaaccaa cttgttccta ttaagtacaa atgggcttgg 120 gaacattatt tgaatggctg cgcaaataac tggctcccta cagagatccc catggggaaa 180 gacatcgaat tatggaagtc ggatcgtctt tctgaagatg agcggcgagt cattcttttg 240 aatttaggtt ttttcagcac cgcagagagc ttggttggga ataatattgt tctagcaatt 300 tttaaacatg taactaatcc ggaagcgaga caatatcttt taagacaagc ttttgaagaa 360 gcggttcaca cgcacacatt tttgtatatt tgtgagtcac tcggattaga cgagaaagaa 420 attttcaatg cctataacga gcgtgctgcg attaaggcca aagatgattt ccagatggaa 480 atcactggca aggtattaga tcctaatttt cgcacggact ctgttgaggg tctacaggag 540 tttgttaaaa acttagtagg atactacatc attatggaag ggattttctt ctatagtggg 600 tttgtgatga tcctttcctt ccacagacaa aataagatga ttggtattgg agaacaatat 660 caatacatct taagagatga gacaatccac ttgaactttg gtattgattt gatcaacggg 720 ataaaagaag agaacccgga gatttggact ccagagttac agcaagaaat tgtcgaatta 780 attaagcgag ctgtcgattt agaaattgag tatgcgcaag actgtctccc tagagggatt 840 ttgggattga gagcttcgat gttcatcgat tatgtgcagc atattgcaga ccgtcgtttg 900 gaaagaatcg gattaaaacc tatttatcat acgaaaaacc cattcccttg gatgagcgaa 960 acaatagacc ttaataaaga gaaaaacttc tttgaaacaa gggttataga atatcaacat 1020 gcagcaagct taacttgg 1038 82 3159 DNA Chlamydia trachomatis serovar D 82 atgtttacaa ggatagttat ggtcgatcta caagaaaagc aatgcacaat tgttaagcgc 60 aatggaatgt ttgttccttt cgatcggaac cgtatttttc aggctttaga agcagctttt 120 cgagacactc gcagaattga tgatcatatg cctttgcctg aagatctgga aagttccata 180 cgctcgataa cgcatcaggt agttaaagaa gttgtgcaaa agattacaga tggacaagtg 240 gttactgtag agcgtatcca agatatggtt gaaagccaac tatatgtgaa tggtttgcaa 300 gatgttgctc gcgattatat tgtctatcgc gatgaccgta aagcgcatcg gaaaaaatct 360 tggcaaagcc tatccgttgt tcgtcgttgt gggactgttg tacactttaa tcctatgaaa 420 atttccgccg ctttggaaaa agctttccga gctaccgata agactgaggg gatgactcca 480 agttctgtgc gagaggaaat caatgctttg acgcaaaaca ttgtcgcgga aatagaagaa 540 tgttgtcctc aacaggatag acgcattgat atcgagaaga ttcaagatat tgttgaacag 600 caactaatgg ttgttgggca ttatgctgtt gcaaagaact atattcttta tcgagaagct 660 cgcgctcgtg ttcgtgataa cagagaagag gacgggagta cagaaaagac tatagcagaa 720 gaagctgttg aggtgctcag taaagacggt tctacctata caatgacgca ttcgcagttg 780 ttggctcatt tagcgcgcgc ttgtagtcgt tttccagaaa cgacagatgc ggcgctgctt 840 accgatatgg ctttcgcaaa tttctattcc ggtatcaaag agtctgaagt agtactggcc 900 tgtattatgg cggctcgtgc caatattgaa aaggagcctg attatgcctt tgttgctgca 960 gagctcttac ttgacgttgt atataaggaa gcgttaggga aatcgaaata tgctgaggat 1020 ttagaacaag cacatcgcga tcatttcaaa cgctacatcg cagaagggga tacctatcgt 1080 ctgaatgctg aactgaaaca tctttttgat ttagacgcgt tagccgatgc tatggatcta 1140 tctcgagatc tacagttttc ttacatgggt attcaaaatc tgtatgatcg ttattttaat 1200 caccacgaag gttgccgttt agaaactccc caaatttttt ggatgcgcgt tgctatgggg 1260 ttggcattga atgagcaaga caagacttct tgggctatta ctttttataa tttgctttcg 1320 acattccgat atacaccagc tacgccaacc ttgttcaatt caggtatgcg gcattctcag 1380 ttaagctctt gctatctttc cactgtacaa gataatttgg tcaatatcta taaggtcatt 1440 gctgataacg ctatgctatc taagtgggca ggagggatag gtaatgattg gacggcgatt 1500 cgtgcaacag gggctttaat taaaggaacc aatggaagaa gtcagggagt aattcctttt 1560 attaaggtga caaatgatac agcagtcgca gtgaatcaag gtggtaaacg caagggagct 1620 gtatgcgtct atttagaagt ttggcacctc gactacgaag atttccttga attgagaaag 1680 aatacagggg atgagcgtcg acgggctcat gatgtcaata tagctagctg gattccagat 1740 cttttcttca aacgtttaca gcaaaaaggg acatggactc tattcagccc agatgatgtt 1800 ccgggattac acgatgctta tggggaagaa tttgagcgtt tgtacgaaga atatgagcgg 1860 aaggttgata ccggagagat tcggttattc aagaaggtag aagctgaaga tctgtggaga 1920 aaaatgctca gcatgctttt tgaaacggga cacccatgga tgacttttaa agatccatcc 1980 aacatccgtt cggctcaaga tcataaaggc gtggtgcgtt gttccaatct gtgtacggag 2040 attttgttaa actgctcgga gacagaaact gctgtttgta atttaggatc gattaactta 2100 gttcaacata tcgtagggga tgggttagat gaggaaaaac tctctgagac gatctctata 2160 gcagtccgta tgttggataa cgtgattgat attaactttt atccaacaaa ggaagctaaa 2220 gaggcgaact ttgctcaccg cgctattgga ttaggggtga tgggattcca agatgccttg 2280 tataagctag atataagcta tgcttcgcaa gaagctgtag aatttgctga ctacagttca 2340 gagttgattt cttactatgc gattcaagct tcttgtctgc tcgctaaaga acgaggcact 2400 tacagctctt ataaaggatc gaaatgggat agaggtttgc tccctattga tacgattcag 2460 ttgttagcga actatcgagg agaagcaaat ctccagatgg atacgtcatc aagaaaagat 2520 tgggaaccta tccgtagttt ggttaaagag catggtatgc gacattgtca gcttatggct 2580 atagctccga cagcgacgat ctccaacatt ataggagtaa ctcaatctat tgagccaacg 2640 tacaaacatt tgtttgtgaa gtctaatttg tccggagaat tcacgattcc aaatgtgtat 2700 ttaattgaga agttgaagaa attaggtatc tgggatgctg atatgttaga tgacctgaaa 2760 tattttgatg ggtctttatt ggaaatcgag cgtataccag atcacttaaa acatattttc 2820 ttgacagctt ttgagattga accagaatgg attatcgaat gcgcgtctcg aagacaaaaa 2880 tggattgata tggggcaatc cctcaacctt tatcttgccc agccagacgg gaaaaaactg 2940 tcgaatatgt atttaacggc ttggaaaaaa ggtttgaaaa ctacgtatta tctgagatct 3000 tcatcagcaa cgaccgttga aaaatctttt gtagatatta ataagagagg aattcagcct 3060 cgttggatga agaataagtc tgcttcggca ggaattattg ttgaaagagc gaagaaagca 3120 cctgtctgtt ctttggaaga agggtgtgaa gcatgtcag 3159 83 4593 DNA Chlamydia trachomatis serovar D 83 atgagttccg agaaagatat aaaaagcacc tgttctaagt tttctttgtc tgtagtagca 60 gctatccttg cctctgttag cgggttagct agttgcgtag atcttcatgc tggaggacag 120 tctgtaaatg agctggtata tgtaggccct caagcggttt tattgttaga ccaaattcga 180 gatctattcg ttgggtctaa agatagtcag gctgaaggac agtataggtt aattgtagga 240 gatccaagtt ctttccaaga gaaagatgcg gatactcttc ccgggaaggt agagcaaagt 300 actttgttct cagtaaccaa tcccgtggtt ttccaaggtg tggaccaaca ggatcaagtc 360 tcttcccaag ggttaatttg tagttttacg agcagcaacc ttgattctcc tcgtgacgga 420 gaatcttttt taggtattgc ttttgttggg gatagtagta aggctggaat cacattaact 480 gacgtgaaag cttctttgtc tggagcggct ttatattcta cagaagatct tatctttgaa 540 aagattaagg gtggattgga atttgcatca tgttcttctc tagaacaggg gggagcttgt 600 gcagctcaaa gtattttgat tcatgattgt caaggattgc aggttaaaca ctgtactaca 660 gccgtgaatg ctgaggggtc tagtgcgaat gatcatcttg gatttggagg aggcgctttc 720 tttgttacgg gttctctttc tggagagaaa agtctctata tgcctgcagg agatatggta 780 gttgcgaatt gtgatggggc tatatctttt gaaggaaaca gcgcgaactt tgctaatgga 840 ggagcgattg ctgcctctgg gaaagtgctt tttgtcgcta atgataaaaa gacttctttt 900 atagagaacc gagctttgtc tggaggagcg attgcagcct cttctgatat tgcctttcaa 960 aactgcgcag aactagtttt caaaggcaat tgtgcaattg gaacagagga taaaggttct 1020 ttaggtggag gggctatatc ttctctaggc accgttcttt tgcaagggaa tcacgggata 1080 acttgtgata agaatgagtc tgcttcgcaa ggaggcgcca tttttggcaa aaattgtcag 1140 atttctgaca acgaggggcc agtggttttc agagatagta cagcttgctt aggaggaggc 1200 gctattgcag ctcaagaaat tgtttctatt cagaacaatc aggctgggat ttccttcgag 1260 ggaggtaagg ctagtttcgg aggaggtatt gcgtgtggat ctttttcttc cgcaggtggt 1320 gcttctgttt tagggaccat tgatatttcg aagaatttag gcgcgatttc gttctctcgt 1380 actttatgta cgacctcaga tttaggacaa atggagtacc agggaggagg agctctattt 1440 ggtgaaaata tttctctttc tgagaatgct ggtgtgctca cctttaaaga caacattgtg 1500 aagacttttg cttcgaatgg gaaaattctg ggaggaggag cgattttagc tactggtaag 1560 gtggaaatta ctaataattc cgaaggaatt tcttttacag gaaatgcgag agctccacaa 1620 gctcttccaa ctcaagagga gtttccttta ttcagcaaaa aagaagggcg accactctct 1680 tcaggatatt ctgggggagg agcgatttta ggaagagaag tagctattct ccacaacgct 1740 gcagtagtat ttgagcaaaa tcgtttgcag tgcagcgaag aagaagcgac attattaggt 1800 tgttgtggag gaggcgctgt tcatgggatg gatagcactt cgattgttgg caactcttca 1860 gtaagatttg gtaataatta cgcaatggga caaggagtct caggaggagc tcttttatct 1920 aaaacagtgc agttagctgg gaatggaagc gtcgattttt ctcgaaatat tgctagtttg 1980 ggaggaggag ctcttcaagc ttctgaagga aattgtgagc tagttgataa cggctatgtg 2040 ctattcagag ataatcgagg gagggtttat gggggtgcta tttcttgctt acgtggagat 2100 gtagtcattt ctggaaacaa gggtagagtt gaatttaaag acaacatagc aacacgtctt 2160 tatgtggaag aaactgtaga aaaggttgaa gaggtagagc cagctcctga gcaaaaagac 2220 aataatgagc tttctttctt agggagagca gaacagagtt ttattactgc agctaatcaa 2280 gctcttttcg catctgaaga tggggattta tcacctgagt catccatttc ttctgaagaa 2340 cttgcgaaaa gaagagagtg tgctggagga gctatttttg caaaacgggt tcgtattgta 2400 gataaccaag aggccgttgt attctcgaat aacttctctg atatttatgg cggcgccatt 2460 tttacaggtt ctcttcgaga agaggataag ttagatgggc aaatccctga agtcttgatc 2520 tcaggcaatg caggggatgt tgttttttcc ggaaattcct cgaagcgtga tgagcatctt 2580 cctcatacag gtgggggagc catttgtact caaaatttga cgatttctca gaatacaggg 2640 aatgttctgt tttataacaa cgtggcctgt tcgggaggag ctgttcgtat agaggatcat 2700 ggtaatgttc ttttagaagc ttttggagga gatattgttt ttaaaggaaa ttcttctttc 2760 agagcacaag gatccgatgc tatctatttt gcaggtaaag aatcgcatat tacagccctg 2820 aatgctacgg aaggacatgc tattgttttc cacgacgcat tagtttttga aaatctagaa 2880 gaaaggaaat ctgctgaagt attgttaatc aatagtcgag aaaatccagg ttacactgga 2940 tctattcgat ttttagaagc agaaagtaaa gttcctcaat gtattcatgt acaacaagga 3000 agccttgagt tgctaaatgg agccacatta tgtagttatg gttttaaaca agatgctgga 3060 gctaagttgg tattggctgc tggagctaaa ctgaagattt tagattcagg aactcctgta 3120 caacaagggc atgctatcag taaacctgaa gcagaaatcg agtcatcttc tgaaccagag 3180 ggtgcacatt ctctttggat tgcgaagaat gctcaaacaa cagttcctat ggttgatatc 3240 catactattt ctgtagattt agcctccttc tcttctagtc aacaggaggg gacagtagaa 3300 gctcctcagg ttattgttcc tggaggaagt tatgttcgat ctggagagct taatttggag 3360 ttagttaaca caacaggtac tggttatgaa aatcatgctt tattgaagaa tgaggctaaa 3420 gttccattga tgtctttcgt tgcttctggt gatgaagctt cagccgaaat cagtaacttg 3480 tcggtttctg atttacagat tcatgtagta actccagaga ttgaagaaga cacatacggc 3540 catatgggag attggtctga ggctaaaatt caagatggaa ctcttgtcat tagttggaat 3600 cctactggat atcgattaga tcctcaaaaa gcaggggctt tagtatttaa tgcattatgg 3660 gaagaagggg ctgtcttgtc tgctctgaaa aatgcacgct ttgctcataa tctcactgct 3720 cagcgtatgg aattcgatta ttctacaaat gtgtggggat tcgcctttgg tggtttccga 3780 actctatctg cagagaatct ggttgctatt gatggataca aaggagctta tggtggtgct 3840 tctgctggag tcgatattca attgatggaa gattttgttc taggagttag tggagctgct 3900 ttcctaggta aaatggatag tcagaagttt gatgcggagg tttctcggaa gggagttgtt 3960 ggttctgtat atacaggatt tttagctgga tcctggttct tcaaaggaca atatagcctt 4020 ggagaaacac agaacgatat gaaaacgcgt tatggagtac taggagagtc gagtgcttct 4080 tggacatctc gaggagtact ggcagatgct ttagttgaat accgaagttt agttggtcct 4140 gtgagaccta ctttttatgc tttgcatttc aatccttatg tcgaagtatc ttatgcttct 4200 atgaaattcc ctggctttac agaacaagga agagaagcgc gttcttttga agacgcttcc 4260 cttaccaata tcaccattcc tttagggatg aagtttgaat tggcgttcat aaaaggacag 4320 ttttcagagg tgaactcttt gggaataagt tatgcatggg aagcttatcg aaaagtagaa 4380 ggaggcgcgg tgcagctttt agaagctggg tttgattggg agggagctcc aatggatctt 4440 cctagacagg agctgcgtgt cgctctggaa aataatacgg aatggagttc ttacttcagc 4500 acagtcttag gattaacagc tttttgtgga ggatttactt ctacagatag taaactagga 4560 tatgaggcga atactggatt gcgattgatc ttt 4593 84 1422 DNA Chlamydia trachomatis serovar D 84 atgaaaatta ttcacacagc tatcgaattt gctccggtaa tcaaagccgg aggcctggga 60 gacgcgctat acggactagc aaaagcttta gccgctaatc acacaacgga agtggtaatc 120 cctttatacc ctaaattatt tactttgccc aaagaacaag atctttgctc gatccaaaaa 180 ttatcttatt tttttgctgg agagcaagaa gcaactgctt tctcctactt ttatgaagga 240 attaaagtaa ctctattcaa actcgacaca cagccagagt tattcgagaa tgcggaaaca 300 atctacacaa gcgatgatgc cttccgtttt tgcgcttttt ctgctgctgc ggcctcctac 360 atccaaaaag aaggagccaa tatcgttcat ttacacgatt ggcatacagg attagttgct 420 ggactactca aacaacagcc ctgctctcaa ttacaaaaga ttgttcttac cctacataat 480 tttggttatc gaggctatac aacacgagaa atattagaag cctcctcttt gaatgaattt 540 tatatcagcc agtaccaact atttcgcgat ccacaaactt gtgtgttgct aaaaggagct 600 ttatactgtt cagatttcgt gactacggtt tctcctacat acgccaaaga aattcttgaa 660 gattattccg attacgaaat tcacgatgcc attactgcta gacaacatca tctccgcggg 720 attttaaatg gaatcgacac gacaatttgg gggcctgaaa cggatcccaa tttagcgaaa 780 aactacacta aagagctttt cgagacccct tcaatttttt ttgaagctaa agccgagaat 840 aaaaaagcct tgtacgaaag attaggcctc tctttagaac actctccttg cgtgtgcatt 900 atttctagaa ttgctgagca gaaaggtcct cactttatga aacaggccat tctccatgca 960 ctagaaaacg cttacacgct cattattata ggtacctgct acgggaatca attgcatgaa 1020 gaatttgcaa atcttcaaga atcattagcg aattcccctg atgtaaggat tcttttgact 1080 tatagtgatg tgctggcacg acaaattttc gccgctgcag atatgatctg cattccttct 1140 atgtttgaac catgtggact cacacaaatg attggaatgc gttacgggac tgtaccgtta 1200 gtaagagcta caggaggact agcagatact gtagcaaatg gaatcaatgg attttccttc 1260 tttaatccgc atgacttcta tgaattccga aacatgcttt cggaagcagt gacaacctac 1320 cgtaccaacc acgacaagtg gcaacatatt gtacgtgctt gtctagattt ttcttcagac 1380 ctagaaactg ccgccaataa atatttagaa atttataaac aa 1422 85 1179 DNA Chlamydia trachomatis serovar D 85 atgaaaaaac tcttgaaatc ggtattagta tttgccgctt tgagttctgc ttcctccttg 60 caagctctgc ctgtggggaa tcctgctgaa ccaagcctta tgatcgacgg aattctgtgg 120 gaaggtttcg gcggagatcc ttgcgatcct tgcgccactt ggtgtgacgc tatcagcatg 180 cgtgttggtt actacggaga ctttgttttc gaccgtgttt tgaaaactga tgtgaataaa 240 gaatttcaga tgggtgccaa gcctacaact gatacaggca atagtgcagc tccatccact 300 cttacagcaa gagagaatcc tgcttacggc cgacatatgc aggatgctga gatgtttaca 360 aatgccgctt gcatggcatt gaatatttgg gatcgttttg atgtattctg tacattagga 420 gccaccagtg gatatcttaa aggaaactct gcttctttca atttagttgg attgtttgga 480 gataatgaaa atcaaaaaac ggtcaaagcg gagtctgtac caaatatgag ctttgatcaa 540 tctgttgttg agttgtatac agatactact tttgcgtgga gcgtcggcgc tcgcgcagct 600 ttgtgggaat gtggatgtgc aactttagga gcttcattcc aatatgctca atctaaacct 660 aaagtagaag aattaaacgt tctctgcaat gcagcagagt ttactattaa taaacctaaa 720 gggtatgtag gtaaggagtt tcctcttgat cttacagcag gaacagatgc tgcgacagga 780 actaaggatg cctctattga ttaccatgaa tggcaagcaa gtttagctct ctcttacaga 840 ctgaatatgt tcactcccta cattggagtt aaatggtctc gagcaagctt tgatgccgat 900 acgattcgta tagcccagcc aaaatcagct acagctattt ttgatactac cacgcttaac 960 ccaactattg ctggagctgg cgatgtgaaa actggcgcag agggtcagct cggagacaca 1020 atgcaaatcg tttccttgca attgaacaag atgaaatcta gaaaatcttg cggtattgca 1080 gtaggaacaa ctattgtgga tgcagacaaa tacgcagtta cagttgagac tcgcttgatc 1140 gatgagagag cagctcacgt aaatgcacaa ttccgcttc 1179 86 585 DNA Chlamydia trachomatis serovar D 86 atgggatcac tagttggaag acaggctccg gatttttctg gtaaagccgt tgtttgtgga 60 gaagagaaag aaatctctct agcagacttt cgtggtaagt atgtagtgct cttcttttat 120 cctaaagatt ttacctatgt ttgtcctaca gaattgcatg cttttcaaga tagattggta 180 gattttgaag agcgaggtgc agtcgtgctt ggttgctccg ttgacgacat tgagacacat 240 tctcgttggc tcgctgtagc gagaaatgca ggaggaatag agggaacaga atatcctctg 300 ttagcagacc cttcttttaa aatatcagaa gcttttggtg ttttgaatcc tgaaggatcg 360 ctcgctttaa gagcgacttt ccttatcgat aaatatgggg ttgttcgtca tgcggttatc 420 aatgatcttc ctttagggcg ttccattgac gaggaattgc gtattttaga ttcattgatc 480 ttctttgaga accacggaat ggtttgtcca gctaactggc gttctggaga gcgtggaatg 540 gtgccttctg aagagggatt aaaagaatat ttccagacga tggat 585 87 258 DNA Chlamydia trachomatis serovar D 87 atgagtcaaa ataagaactc tgctttcatg cagcctgtga acgtatccgc tgatttagct 60 gccatcgttg gtgcaggacc tatgcctcgc acagagatca ttaagaaaat gtgggattac 120 attaagaaga atggccttca agatcctaca aacaaacgta atatcaatcc cgatgataaa 180 ttggctaaag tttttggaac tgaaaaacct atcgatatgt tccaaatgac aaaaatggtt 240 tctcaacaca tcattaaa 258 88 1182 DNA Chlamydia trachomatis serovar D 88 atgtcaaaag aaacttttca acgtaataag cctcatatca acatagggac cattggccac 60 gttgaccatg gtaagactac gttgacagct gctattacgc gtgcgttgtc tggagatggg 120 ttggctgatt ttcgtgatta tagctctatt gacaacactc ctgaagaaaa agctcgcggt 180 attacaatta acgcttccca cgttgagtac gaaacagcta atcgtcacta cgctcacgtg 240 gactgccctg gtcacgctga ctatgttaaa aacatgatca ccggtgcagc tcaaatggac 300 ggggctattc tagtagtttc tgcaacagac ggagctatgc ctcaaactaa agagcatatt 360 cttttggcaa gacaagttgg ggttccttac atcgttgttt ttctcaataa aattgacatg 420 atttccgaag aagacgctga attggtcgac ttagttgaga tggagttggt tgagcttctt 480 gaagagaaag gatacaaagg gtgtccaatc atcagaggtt ctgctctgaa agctttggaa 540 ggggatgctg catacataga gaaagttcga gagctaatgc aagccgtcga tgataacatc 600 cctactccag aaagagaaat tgacaagcct ttcttaatgc ctattgagga cgtattctct 660 atctccggac gaggaactgt agtaactgga cgtattgagc gtggaattgt taaagtttcc 720 gataaagttc agttggtcgg tcttagagat actaaagaaa cgattgttac tggggttgaa 780 atgttcagaa aagaactccc agaaggtcgt gcaggagaga acgttggatt gctcctcaga 840 ggtattggta agaacgatgt ggaaagagga atggttgttt gcttgccaaa cagtgttaaa 900 cctcatacac agttcaagtg tgctgtttac gttttgcaaa aagaagaagg tggacgacat 960 aagcctttct tcacaggata tagacctcaa ttcttcttcc gtacaacaga cgtcacaggt 1020 gtggtaactc tgcctgaggg aattgagatg gtcatgcctg gggataacgt tgagtttgaa 1080 gtgcaattga ttagccctgt ggctttagaa gaaggtatga gatttgcgat tcgtgaaggt 1140 ggtcgtacaa tcggtgctgg aactatttct aagatcattg ca 1182 89 246 DNA Chlamydia trachomatis serovar D 89 atggggcaag atcaccgaag aaaatttctt aagaaagtat cttttgtaaa aaaacaagca 60 gcttttgcgg gtaactttat cgaagaaatt aagaagattg agtgggtaaa taagcgagat 120 cttaaaagat acgtcaagat tgttttgatg aatatttttg gctttggatt ttccatctat 180 tgtgtggatt tagctcttcg aaagtccctt tcattgttcg gtaaagtaac aagctttttc 240 tttggt 246 90 1137 DNA Chlamydia trachomatis serovar D 90 atggtgatcc ctaaggtgga tctaggagaa agtgccgtca tgatgggtta caagcttact 60 tcgcaacttg ctatgctttc gatcttattg actttcaccc atactatggg tcatgcaagt 120 cagatgagcc aaactcttcc tactattata gaagcacaag cggaagaggc attgcaggct 180 gacaggggag ttgctggaca ggctcttaaa aaacttcgta aaaaaagatg tgcttctaga 240 aaatctgcat gtaaggcttc ttttaagaaa aaggatttct tttcttgtat tacaaatgga 300 ttgttctctg gaaatcatga gcagcgttta actgcgaaaa aagagaacaa ggctcgaggt 360 aaagagcctc gagtagtggt tcaaacgact aaaaaacgac aaataactca gtctgagaaa 420 gaatttttcg attggctatg taatagtaaa agagaaagaa agcttctcaa gaaaaagcct 480 gtaaatactt ctcttgctaa gagtgaagaa ttgagtccta aagaagcagc aatagctgct 540 gctcgagctt ctctttctcc agaagaaaaa cgtcaattga ttcgtgagtg gttagcagaa 600 gaaaagactg ctcgtaaatc tgggcgtgcg gcttgtgcgg taagtgagaa tcttaaaaga 660 gacggaagta ttacttctac attgcgctat gatgcggaga aagctttgac tacacgtgta 720 aaacgcaatg aaaattctgt aaatgctaga gcaagacaac gagccgctct tcaaaaagcc 780 aagaaagcaa agacggagaa acctgaggct gatgagaaag ctgcagaagc tgttgccgca 840 gctccaacca aacaggcgca taaggagcca gagaattact tcgcagctac agcttctaca 900 aataatacta atgttatgtc ctatctaaat gctcatcaat accgttgtga ttcttcggag 960 acggactggc cttgctcttc ttgtgttacg aaacgccgag ctaacttcgg tatttctgtg 1020 tgtactatgg tggttaccgt cattgctatg atcgtaggag ctgttatcat ttctaatgct 1080 acagactcta ccgttgcggg ctcctcggga acaggaggag gaggctcaac gcaacca 1137 91 1689 DNA Chlamydia trachomatis serovar D 91 atggtttatt ttagagctca tcaacctagg catacgccta aaacatttcc tttggaagtt 60 caccattcgt tctccgataa gcatcctcaa attgctaaag ctatgcggat tacggggata 120 gccctcgcag ctctatctct gctcgctgta gtcgcctgcg ttattgccgt ctctgcggga 180 ggagctgcca ttcctcttgc tgtcattagt ggaattgctg taatgtctgg cctcttatcc 240 gctgccacca ttatctgttc tgcaaaaaag gctttggctc aacgaaaaca aaaacaacta 300 gaagagtcgc ttccgttaga taatgcgacc gagcatgtga gttacctgac ctcagacacc 360 tcttatttta atcaatggga atccttaggt gctctaaata agcagttgtc tcagattgac 420 ttaactattc aagctcccga aaaaaaacta ttaaaagaag ttcttggttc cagatacgat 480 tccattaatc actccatcga agagatctcc gatcgcttta cgaaaatgct ctctcttctt 540 cgattaagag aacattttta tcgaggagaa gagcgttatg ccccctattt aagccctcct 600 ctacttaaca agaatcgttt gctgacccaa atcacatcca atatgattag gatgctacca 660 aaatccggtg gtgttttttc cctcaaagcc aatacactaa gtcatgccag ccgcacacta 720 tatacagtat taaaagtcgc tttatcctta ggagttctcg ctggagtcgc tgctcttatc 780 atctttcttc cccctagcct gccttttatc gctgttatag gagtatcttc cttagcattg 840 gggatggcat ctttccttat gattcggggc attaagtatt tgctcgaaca ttctcctctg 900 aatagaaagc aactagctaa agatattcaa aaaaccattg gcccagatgt cttggcctct 960 atggttcatt accagcatca attactatca catctacatg aaactctatt agatgaagcc 1020 atcacagcta gatggagcga gcccttcttt attgaacacg ctaatcttaa ggcaaaaatt 1080 gaagatttga caaaacaata tgatatattg aacgcagcct ttaataaatc tttacaacaa 1140 gatgaggcgc tccgttctca attagagaaa cgagcttact tattcccaat tcctaataac 1200 gacgaaaatg ctaaaactaa agaatcgcag cttctagact cagaaaatga ttcaaattct 1260 gaatttcagg agattataaa taaaggacta gaagctgcca ataaacgacg agctgacgct 1320 aagtcaaaat tctatacgga agacgaaacc tctgacaaaa tattctctat atggaaaccc 1380 acaaagaact tggcattaga agatttgtgg agagtgcatg aagcttgcaa tgaagagcaa 1440 caagctctcc tcttagaaga ttatatgagt tataaaacct cagaatgtca agctgcactc 1500 caaaaagtga gtcaagaact gaaggcggca caaaaatcat tcgcagtcct agaaaagcat 1560 gctctagaca gatcttatga atccagtgta gccacgatgg atttagctag agcgaatcaa 1620 gaaacacacc ggcttctgaa catcctctct gaattacaac aactagcaca atacctgtta 1680 gataatcac 1689 92 1074 DNA Chlamydia trachomatis serovar D 92 gtgcgtaaaa ctgtcattgt tgctatgtct ggaggagtgg attcctcggt tgttgcttat 60 ctcttaaaga agcaagggga gtataatgtt gttgggctct tcatgaaaaa ttggggagag 120 caggacgaga atggtgagtg tactgcaacc aaagattttc gcgatgtaga gcggatcgca 180 gaacaattgt ccattccata ttacacagtt tccttttcta aggaatataa agagcgagtg 240 ttttctagat ttctaagaga atatgcgaac ggctacactc ccaatcctga tgtgttatgc 300 aatcgagaaa tcaaatttga tttattacag aagaaggtac gtgagctaaa aggtgatttt 360 ttagccacgg gacattattg tcgaggaggg gctgatggaa ctggtttgtc cagaggaata 420 gaccccaata aagaccaaag ttatttctta tgtggcactc ctaaggatgc tttatccaat 480 gtacttttcc ccctgggagg tatgtataaa acggaggtac gtcgaattgc tcaagaagct 540 ggtttagcta ccgccacaaa aaaagatagc acagggattt gcttcattgg taaacggcct 600 tttaagagtt tccttgagca gtttgtagca gactctcctg gagacattat tgattttgat 660 acacaacagg tagtcggccg acatgaagga gcccattatt atacgattgg acagcgtcga 720 gggttaaaca taggaggaat ggaaaagcct tgttatgttc ttagcaagaa tatggaaaag 780 aatattgttt acattgtaag gggtgaagat catcctttac tttatcgaca agagctttta 840 gctaaggaac ttaattggtt tgttcccttg caggagccta tgatctgtag tgctaaagtt 900 cggtacagat cccctgacga gaaatgttct gtatatcctt tggaagatgg aacggtaaaa 960 gtgattttcg atgtccctgt gaaagctgtc acccctggac agactgtagc tttctaccag 1020 ggggacattt gtttaggagg aggagtgatt gaagtgccta tgattcatca gctg 1074 93 801 DNA Chlamydia trachomatis serovar D 93 atgtccagaa aaccggcttc taactcatcc cggaacacca aacggtcctc agacacttcc 60 tgggaagtca ttgcccaaga ttataataaa gccgttgatc gcgatggaca tttctatcat 120 aaggaagtga ttctccctaa tctcctttct aagctacata tttcccgctc atcgtctctg 180 gttgatgtag gatgtggtca agggattttg gagaagcatt tacccaaaca tctcccttat 240 ctaggaatcg atctttcccc tagtctgctg cgttttgcaa agaaaagcgc ttcctcaaaa 300 tcacgtcgct ttcttcatca cgatatgacg caaccggtac cagcagatca tcatgagcag 360 ttttcccatg ctacagcaat cctttctctt cagaatatgg aatctccaga acaagctatc 420 gcacacacag cgaatctttt ggctcctcaa ggtaggttgt ttattgttct caaccatcca 480 tgctttcgca tccctaggct ttcttcatgg ctttatgatg agcctaaaaa actcttatct 540 agaaaaatag accgctatct ctctcctgtg gcggttccta tcgttgtgca tcctggagaa 600 aaacattctg agacgacata ttctttccat ttccccttaa gctattgggt acaagcttta 660 tctaatcaca atcttctgat tgatagtatg gaagaatgga tctcccctaa aaaatcctca 720 gggaagaggg ctcgagcaga aaatctttgt cgcaaggagt ttccgctttt cttgtttatc 780 tcagcattaa aaatatcaaa a 801 94 2601 DNA Chlamydia trachomatis serovar D 94 atggagaaat tttcagatgc agtaagcgaa gccttagaaa aggcgtttga gttagctaaa 60 aactctaagc attcctacgt gacagaaaac catttgctga aaagtctttt gcaaaatcca 120 ggttccctat tttgtttggt cattaaggat gtgcacggta atcttggttt gcttacttct 180 gctgtggacg acgccttacg cagagaacca actgtagtcg agggaaccgc tgttgctagt 240 ccttctccaa gtttacagca gttgttgctc aatgcgcatc aagaagctag aagtatgggt 300 gacgaatatc tatcagggga tcatttgtta ctagcttttt ggcgatcgac taaagagcct 360 tttgcttctt ggagaaaaac tgtaaaaact acctctgaag cgttgaaaga attaattact 420 aaattaagac aaggaagtcg tatggactca cctagtgctg aagaaaatct gaaaggatta 480 gagaaatact gcaaaaattt gactgtactt gcaagagaag gcaagcttga tcctgtgatt 540 ggtcgagatg aagagattag acgtacgata caggttcttt ctagacgaac aaagaataat 600 cctatgttga taggggagcc cggagttggg aaaacagcaa tcgctgaagg acttgctctt 660 cgcatagtgc aaggggatgt tccagagagt ttaaaggaaa agcatctgta tgtactggat 720 atgggagctt tgattgcagg tgccaagtat cgaggagagt ttgaagagcg gttaaaaagt 780 gtattgaagg gtgtagaagc ttctgaaggc gagtgtatcc tattcattga tgaagtgcat 840 actttagtag gagcgggagc tacagatgga gctatggatg cagcgaatct attaaagcct 900 gctttagcac gaggcacttt gcattgtatt ggcgctacga ctttgaatga ataccaaaaa 960 tatatagaga aagacgcggc tttggaacgg cgtttccagc ctatttttgt aacagaacct 1020 tctttggaag atgctgtatt cattctccgg gggttaaggg aaaaatatga aatttttcat 1080 ggtgtgcgca ttacagaagg ggctttgaat gcagctgtag ttctttctta tcgttacatc 1140 acagaccgat ttcttcctga taaggcgatt gacctaattg atgaggctgc gagtttaatc 1200 cgtatgcaaa taggaagttt acctctgcct attgatgaaa aggaaagaga attatcagct 1260 ttaatcgtga aacaagaagc tattaaacgc gagcaagcac cagcttatca ggaagaggct 1320 gaagacatgc aaaaagcaat tgaccgggtt aaggaagagc tggccgcttt acgcttgcgc 1380 tgggatgaag aaaaaggatt aattacagga ttaaaagaaa agaagaatgc tttagaaaat 1440 ttaaaatttg ccgaagagga agctgagcgt actgccgatt acaatcgggt ggcagaacta 1500 cgctatagtt tgattccttc tttggaggaa gaaattcatt tagctgagga agctttaaat 1560 caaagagatg ggcgcctgct tcaagaggaa gttgatgagc ggttgattgc gcaagttgtt 1620 gcgaattgga ctggaatccc tgtgcaaaaa atgttggagg gagaatctga aaagttattg 1680 gtgttggagg agtctttaga agaaagggtt gttggacaac ctttcgctat tgccgcagtc 1740 agtgattcga ttcgagctgc tcgagtagga ttgagtgatc cgcagcgtcc tctaggagtg 1800 tttctatttc ttggacctac aggggtaggg aaaactgagc ttgctaaagc attagcagag 1860 cttttattta ataaggaaga agcgatgatt cggtttgaca tgaccgaata tatggaaaaa 1920 cattccgttt ccaaattgat aggatctcct ccagggtatg taggatatga agaaggaggg 1980 agtctctcag aagctttaag aagacgacct tattctgttg ttctttttga tgagatagaa 2040 aaagcagata aagaagtatt taatatttta ttgcagattt ttgatgatgg gattcttacg 2100 gatagcaaga agcgtaaggt aaattgtaag aatgctcttt tcattatgac atcaaatatt 2160 ggttcgcaag agcttgctga ttattgtact aagaaaggaa ctatcgtaga caaagaagct 2220 gtgctatctg ttgttgcccc tgcgcttaaa aattatttta gtccagaatt tatcaatcgt 2280 atcgatgaca ttctgccttt cgttcctttg actacggaag acattgtaaa aattgtcggt 2340 attcaaatga atcgggttgc tttacgtttg ctggaaagaa aaatttcgtt aacttgggat 2400 gattctttag tgctatttct cagtgagcaa ggttatgaca gcgcttttgg agctcgccct 2460 ctgaagcgtt tgatacagca aaaagtagtg actatgttgt ctaaagctct tttgaaagga 2520 gatatcaaac ctggaatggc ggtggagctt actatggcaa aagatgtagt tgtgtttaaa 2580 attaaaacaa atccagctgt g 2601 95 1016 PRT Chlamydia trachomatis serovar D 95 Met Pro Phe Ser Leu Arg Ser Thr Ser Phe Cys Phe Leu Ala Cys Leu 5 10 15 Cys Ser Tyr Ser Tyr Gly Phe Ala Ser Ser Pro Gln Val Leu Thr Pro 20 25 30 Asn Val Thr Thr Pro Phe Lys Gly Asp Asp Val Tyr Leu Asn Gly Asp 35 40 45 Cys Ala Phe Val Asn Val Tyr Ala Gly Ala Glu Asn Gly Ser Ile Ile 50 55 60 Ser Ala Asn Gly Asp Asn Leu Thr Ile Thr Gly Gln Asn His Thr Leu 65 70 75 80 Ser Phe Thr Asp Ser Gln Gly Pro Val Leu Gln Asn Tyr Ala Phe Ile 85 90 95 Ser Ala Gly Glu Thr Leu Thr Leu Lys Asp Phe Ser Ser Leu Met Phe 100 105 110 Ser Lys Asn Val Ser Cys Gly Glu Lys Gly Met Ile Ser Gly Lys Thr 115 120 125 Val Ser Ile Ser Gly Ala Gly Glu Val Ile Phe Trp Asp Asn Ser Val 130 135 140 Gly Tyr Ser Pro Leu Ser Ile Val Pro Ala Ser Thr Pro Thr Pro Pro 145 150 155 160 Ala Pro Ala Pro Ala Pro Ala Ala Ser Ser Ser Leu Ser Pro Thr Val 165 170 175 Ser Asp Ala Arg Lys Gly Ser Ile Phe Ser Val Glu Thr Ser Leu Glu 180 185 190 Ile Ser Gly Val Lys Lys Gly Val Met Phe Asp Asn Asn Ala Gly Asn 195 200 205 Phe Gly Thr Val Phe Arg Gly Asn Ser Asn Asn Asn Ala Gly Ser Gly 210 215 220 Gly Ser Gly Ser Ala Thr Thr Pro Ser Phe Thr Val Lys Asn Cys Lys 225 230 235 240 Gly Lys Val Ser Phe Thr Asp Asn Val Ala Ser Cys Gly Gly Gly Val 245 250 255 Val Tyr Lys Gly Thr Val Leu Phe Lys Asp Asn Glu Gly Gly Ile Phe 260 265 270 Phe Arg Gly Asn Thr Ala Tyr Asp Asp Leu Gly Ile Leu Ala Ala Thr 275 280 285 Ser Arg Asp Gln Asn Thr Glu Thr Gly Gly Gly Gly Gly Val Ile Cys 290 295 300 Ser Pro Asp Asp Ser Val Lys Phe Glu Gly Asn Lys Gly Ser Ile Val 305 310 315 320 Phe Asp Tyr Asn Phe Ala Lys Gly Arg Gly Gly Ser Ile Leu Thr Lys 325 330 335 Glu Phe Ser Leu Val Ala Asp Asp Ser Val Val Phe Ser Asn Asn Thr 340 345 350 Ala Glu Lys Gly Gly Gly Ala Ile Tyr Ala Pro Thr Ile Asp Ile Ser 355 360 365 Thr Asn Gly Gly Ser Ile Leu Phe Glu Arg Asn Arg Ala Ala Glu Gly 370 375 380 Gly Ala Ile Cys Val Ser Glu Ala Ser Ser Gly Ser Thr Gly Asn Leu 385 390 395 400 Thr Leu Ser Ala Ser Asp Gly Asp Ile Val Phe Ser Gly Asn Met Thr 405 410 415 Ser Asp Arg Pro Gly Glu Arg Ser Ala Ala Arg Ile Leu Ser Asp Gly 420 425 430 Thr Thr Val Ser Leu Asn Ala Ser Gly Leu Ser Lys Leu Ile Phe Tyr 435 440 445 Asp Pro Val Val Gln Asn Asn Ser Ala Ala Gly Ala Ser Thr Pro Ser 450 455 460 Pro Ser Ser Ser Ser Met Pro Gly Ala Val Thr Ile Asn Gln Ser Gly 465 470 475 480 Asn Gly Ser Val Ile Phe Thr Ala Glu Ser Leu Thr Pro Ser Glu Lys 485 490 495 Leu Gln Val Leu Asn Ser Thr Ser Asn Phe Pro Gly Ala Leu Thr Val 500 505 510 Ser Gly Gly Glu Leu Val Val Thr Glu Gly Ala Thr Leu Thr Thr Gly 515 520 525 Thr Ile Thr Ala Thr Ser Gly Arg Val Thr Leu Gly Ser Gly Ala Ser 530 535 540 Leu Ser Ala Val Ala Gly Ala Ala Asn Asn Asn Tyr Thr Cys Thr Val 545 550 555 560 Ser Lys Leu Gly Ile Asp Leu Glu Ser Phe Leu Thr Pro Asn Tyr Lys 565 570 575 Thr Ala Ile Leu Gly Ala Asp Gly Thr Val Thr Val Asn Ser Gly Ser 580 585 590 Thr Leu Asp Leu Val Met Glu Ser Glu Ala Glu Val Tyr Asp Asn Pro 595 600 605 Leu Phe Val Gly Ser Leu Thr Ile Pro Phe Val Thr Leu Ser Ser Ser 610 615 620 Ser Ala Ser Asn Gly Val Thr Lys Asn Ser Val Thr Ile Asn Asp Ala 625 630 635 640 Asp Ala Ala His Tyr Gly Tyr Gln Gly Ser Trp Ser Ala Asp Trp Thr 645 650 655 Lys Pro Pro Leu Ala Pro Asp Ala Lys Gly Met Val Pro Pro Asn Thr 660 665 670 Asn Asn Thr Leu Tyr Leu Thr Trp Arg Pro Ala Ser Asn Tyr Gly Glu 675 680 685 Tyr Arg Leu Asp Pro Gln Arg Lys Gly Glu Leu Val Pro Asn Ser Leu 690 695 700 Trp Val Ala Gly Ser Ala Leu Arg Thr Phe Thr Asn Gly Leu Lys Glu 705 710 715 720 His Tyr Val Ser Arg Asp Val Gly Phe Val Ala Ser Leu His Ala Leu 725 730 735 Gly Asp Tyr Ile Leu Asn Tyr Thr Gln Asp Asp Arg Asp Gly Phe Leu 740 745 750 Ala Arg Tyr Gly Gly Phe Gln Ala Thr Ala Ala Ser His Tyr Glu Asn 755 760 765 Gly Ser Ile Phe Gly Val Ala Phe Gly Gln Leu Tyr Gly Gln Thr Lys 770 775 780 Ser Arg Met Tyr Tyr Ser Lys Asp Ala Gly Asn Met Thr Met Leu Ser 785 790 795 800 Cys Phe Gly Arg Ser Tyr Val Asp Ile Lys Gly Thr Glu Thr Val Met 805 810 815 Tyr Trp Glu Thr Ala Tyr Gly Tyr Ser Val His Arg Met His Thr Gln 820 825 830 Tyr Phe Asn Asp Lys Thr Gln Lys Phe Asp His Ser Lys Cys His Trp 835 840 845 His Asn Asn Asn Tyr Tyr Ala Phe Val Gly Ala Glu His Asn Phe Leu 850 855 860 Glu Tyr Cys Ile Pro Thr Arg Gln Phe Ala Arg Asp Tyr Glu Leu Thr 865 870 875 880 Gly Phe Met Arg Phe Glu Met Ala Gly Gly Trp Ser Ser Ser Thr Arg 885 890 895 Glu Thr Gly Ser Leu Thr Arg Tyr Phe Ala Arg Gly Ser Gly His Asn 900 905 910 Met Ser Leu Pro Ile Gly Ile Val Ala His Ala Val Ser His Val Arg 915 920 925 Arg Ser Pro Pro Ser Lys Leu Thr Leu Asn Met Gly Tyr Arg Pro Asp 930 935 940 Ile Trp Arg Val Thr Pro His Cys Asn Met Glu Ile Ile Ala Asn Gly 945 950 955 960 Val Lys Thr Pro Ile Gln Gly Ser Pro Leu Ala Arg His Ala Phe Phe 965 970 975 Leu Glu Val His Asp Thr Leu Tyr Ile His His Phe Gly Arg Ala Tyr 980 985 990 Met Asn Tyr Ser Leu Asp Ala Arg Arg Arg Gln Thr Ala His Phe Val 995 1000 1005 Ser Met Gly Leu Asn Arg Ile Phe 1010 1015 96 346 PRT Chlamydia trachomatis serovar D 96 Met Gln Ala Asp Ile Leu Asp Gly Lys Gln Lys Arg Val Asn Leu Asn 5 10 15 Ser Lys Arg Leu Val Asn Cys Asn Gln Val Asp Val Asn Gln Leu Val 20 25 30 Pro Ile Lys Tyr Lys Trp Ala Trp Glu His Tyr Leu Asn Gly Cys Ala 35 40 45 Asn Asn Trp Leu Pro Thr Glu Ile Pro Met Gly Lys Asp Ile Glu Leu 50 55 60 Trp Lys Ser Asp Arg Leu Ser Glu Asp Glu Arg Arg Val Ile Leu Leu 65 70 75 80 Asn Leu Gly Phe Phe Ser Thr Ala Glu Ser Leu Val Gly Asn Asn Ile 85 90 95 Val Leu Ala Ile Phe Lys His Val Thr Asn Pro Glu Ala Arg Gln Tyr 100 105 110 Leu Leu Arg Gln Ala Phe Glu Glu Ala Val His Thr His Thr Phe Leu 115 120 125 Tyr Ile Cys Glu Ser Leu Gly Leu Asp Glu Lys Glu Ile Phe Asn Ala 130 135 140 Tyr Asn Glu Arg Ala Ala Ile Lys Ala Lys Asp Asp Phe Gln Met Glu 145 150 155 160 Ile Thr Gly Lys Val Leu Asp Pro Asn Phe Arg Thr Asp Ser Val Glu 165 170 175 Gly Leu Gln Glu Phe Val Lys Asn Leu Val Gly Tyr Tyr Ile Ile Met 180 185 190 Glu Gly Ile Phe Phe Tyr Ser Gly Phe Val Met Ile Leu Ser Phe His 195 200 205 Arg Gln Asn Lys Met Ile Gly Ile Gly Glu Gln Tyr Gln Tyr Ile Leu 210 215 220 Arg Asp Glu Thr Ile His Leu Asn Phe Gly Ile Asp Leu Ile Asn Gly 225 230 235 240 Ile Lys Glu Glu Asn Pro Glu Ile Trp Thr Pro Glu Leu Gln Gln Glu 245 250 255 Ile Val Glu Leu Ile Lys Arg Ala Val Asp Leu Glu Ile Glu Tyr Ala 260 265 270 Gln Asp Cys Leu Pro Arg Gly Ile Leu Gly Leu Arg Ala Ser Met Phe 275 280 285 Ile Asp Tyr Val Gln His Ile Ala Asp Arg Arg Leu Glu Arg Ile Gly 290 295 300 Leu Lys Pro Ile Tyr His Thr Lys Asn Pro Phe Pro Trp Met Ser Glu 305 310 315 320 Thr Ile Asp Leu Asn Lys Glu Lys Asn Phe Phe Glu Thr Arg Val Ile 325 330 335 Glu Tyr Gln His Ala Ala Ser Leu Thr Trp 340 345 97 1053 PRT Chlamydia trachomatis serovar D 97 Met Phe Thr Arg Ile Val Met Val Asp Leu Gln Glu Lys Gln Cys Thr 5 10 15 Ile Val Lys Arg Asn Gly Met Phe Val Pro Phe Asp Arg Asn Arg Ile 20 25 30 Phe Gln Ala Leu Glu Ala Ala Phe Arg Asp Thr Arg Arg Ile Asp Asp 35 40 45 His Met Pro Leu Pro Glu Asp Leu Glu Ser Ser Ile Arg Ser Ile Thr 50 55 60 His Gln Val Val Lys Glu Val Val Gln Lys Ile Thr Asp Gly Gln Val 65 70 75 80 Val Thr Val Glu Arg Ile Gln Asp Met Val Glu Ser Gln Leu Tyr Val 85 90 95 Asn Gly Leu Gln Asp Val Ala Arg Asp Tyr Ile Val Tyr Arg Asp Asp 100 105 110 Arg Lys Ala His Arg Lys Lys Ser Trp Gln Ser Leu Ser Val Val Arg 115 120 125 Arg Cys Gly Thr Val Val His Phe Asn Pro Met Lys Ile Ser Ala Ala 130 135 140 Leu Glu Lys Ala Phe Arg Ala Thr Asp Lys Thr Glu Gly Met Thr Pro 145 150 155 160 Ser Ser Val Arg Glu Glu Ile Asn Ala Leu Thr Gln Asn Ile Val Ala 165 170 175 Glu Ile Glu Glu Cys Cys Pro Gln Gln Asp Arg Arg Ile Asp Ile Glu 180 185 190 Lys Ile Gln Asp Ile Val Glu Gln Gln Leu Met Val Val Gly His Tyr 195 200 205 Ala Val Ala Lys Asn Tyr Ile Leu Tyr Arg Glu Ala Arg Ala Arg Val 210 215 220 Arg Asp Asn Arg Glu Glu Asp Gly Ser Thr Glu Lys Thr Ile Ala Glu 225 230 235 240 Glu Ala Val Glu Val Leu Ser Lys Asp Gly Ser Thr Tyr Thr Met Thr 245 250 255 His Ser Gln Leu Leu Ala His Leu Ala Arg Ala Cys Ser Arg Phe Pro 260 265 270 Glu Thr Thr Asp Ala Ala Leu Leu Thr Asp Met Ala Phe Ala Asn Phe 275 280 285 Tyr Ser Gly Ile Lys Glu Ser Glu Val Val Leu Ala Cys Ile Met Ala 290 295 300 Ala Arg Ala Asn Ile Glu Lys Glu Pro Asp Tyr Ala Phe Val Ala Ala 305 310 315 320 Glu Leu Leu Leu Asp Val Val Tyr Lys Glu Ala Leu Gly Lys Ser Lys 325 330 335 Tyr Ala Glu Asp Leu Glu Gln Ala His Arg Asp His Phe Lys Arg Tyr 340 345 350 Ile Ala Glu Gly Asp Thr Tyr Arg Leu Asn Ala Glu Leu Lys His Leu 355 360 365 Phe Asp Leu Asp Ala Leu Ala Asp Ala Met Asp Leu Ser Arg Asp Leu 370 375 380 Gln Phe Ser Tyr Met Gly Ile Gln Asn Leu Tyr Asp Arg Tyr Phe Asn 385 390 395 400 His His Glu Gly Cys Arg Leu Glu Thr Pro Gln Ile Phe Trp Met Arg 405 410 415 Val Ala Met Gly Leu Ala Leu Asn Glu Gln Asp Lys Thr Ser Trp Ala 420 425 430 Ile Thr Phe Tyr Asn Leu Leu Ser Thr Phe Arg Tyr Thr Pro Ala Thr 435 440 445 Pro Thr Leu Phe Asn Ser Gly Met Arg His Ser Gln Leu Ser Ser Cys 450 455 460 Tyr Leu Ser Thr Val Gln Asp Asn Leu Val Asn Ile Tyr Lys Val Ile 465 470 475 480 Ala Asp Asn Ala Met Leu Ser Lys Trp Ala Gly Gly Ile Gly Asn Asp 485 490 495 Trp Thr Ala Ile Arg Ala Thr Gly Ala Leu Ile Lys Gly Thr Asn Gly 500 505 510 Arg Ser Gln Gly Val Ile Pro Phe Ile Lys Val Thr Asn Asp Thr Ala 515 520 525 Val Ala Val Asn Gln Gly Gly Lys Arg Lys Gly Ala Val Cys Val Tyr 530 535 540 Leu Glu Val Trp His Leu Asp Tyr Glu Asp Phe Leu Glu Leu Arg Lys 545 550 555 560 Asn Thr Gly Asp Glu Arg Arg Arg Ala His Asp Val Asn Ile Ala Ser 565 570 575 Trp Ile Pro Asp Leu Phe Phe Lys Arg Leu Gln Gln Lys Gly Thr Trp 580 585 590 Thr Leu Phe Ser Pro Asp Asp Val Pro Gly Leu His Asp Ala Tyr Gly 595 600 605 Glu Glu Phe Glu Arg Leu Tyr Glu Glu Tyr Glu Arg Lys Val Asp Thr 610 615 620 Gly Glu Ile Arg Leu Phe Lys Lys Val Glu Ala Glu Asp Leu Trp Arg 625 630 635 640 Lys Met Leu Ser Met Leu Phe Glu Thr Gly His Pro Trp Met Thr Phe 645 650 655 Lys Asp Pro Ser Asn Ile Arg Ser Ala Gln Asp His Lys Gly Val Val 660 665 670 Arg Cys Ser Asn Leu Cys Thr Glu Ile Leu Leu Asn Cys Ser Glu Thr 675 680 685 Glu Thr Ala Val Cys Asn Leu Gly Ser Ile Asn Leu Val Gln His Ile 690 695 700 Val Gly Asp Gly Leu Asp Glu Glu Lys Leu Ser Glu Thr Ile Ser Ile 705 710 715 720 Ala Val Arg Met Leu Asp Asn Val Ile Asp Ile Asn Phe Tyr Pro Thr 725 730 735 Lys Glu Ala Lys Glu Ala Asn Phe Ala His Arg Ala Ile Gly Leu Gly 740 745 750 Val Met Gly Phe Gln Asp Ala Leu Tyr Lys Leu Asp Ile Ser Tyr Ala 755 760 765 Ser Gln Glu Ala Val Glu Phe Ala Asp Tyr Ser Ser Glu Leu Ile Ser 770 775 780 Tyr Tyr Ala Ile Gln Ala Ser Cys Leu Leu Ala Lys Glu Arg Gly Thr 785 790 795 800 Tyr Ser Ser Tyr Lys Gly Ser Lys Trp Asp Arg Gly Leu Leu Pro Ile 805 810 815 Asp Thr Ile Gln Leu Leu Ala Asn Tyr Arg Gly Glu Ala Asn Leu Gln 820 825 830 Met Asp Thr Ser Ser Arg Lys Asp Trp Glu Pro Ile Arg Ser Leu Val 835 840 845 Lys Glu His Gly Met Arg His Cys Gln Leu Met Ala Ile Ala Pro Thr 850 855 860 Ala Thr Ile Ser Asn Ile Ile Gly Val Thr Gln Ser Ile Glu Pro Thr 865 870 875 880 Tyr Lys His Leu Phe Val Lys Ser Asn Leu Ser Gly Glu Phe Thr Ile 885 890 895 Pro Asn Val Tyr Leu Ile Glu Lys Leu Lys Lys Leu Gly Ile Trp Asp 900 905 910 Ala Asp Met Leu Asp Asp Leu Lys Tyr Phe Asp Gly Ser Leu Leu Glu 915 920 925 Ile Glu Arg Ile Pro Asp His Leu Lys His Ile Phe Leu Thr Ala Phe 930 935 940 Glu Ile Glu Pro Glu Trp Ile Ile Glu Cys Ala Ser Arg Arg Gln Lys 945 950 955 960 Trp Ile Asp Met Gly Gln Ser Leu Asn Leu Tyr Leu Ala Gln Pro Asp 965 970 975 Gly Lys Lys Leu Ser Asn Met Tyr Leu Thr Ala Trp Lys Lys Gly Leu 980 985 990 Lys Thr Thr Tyr Tyr Leu Arg Ser Ser Ser Ala Thr Thr Val Glu Lys 995 1000 1005 Ser Phe Val Asp Ile Asn Lys Arg Gly Ile Gln Pro Arg Trp Met Lys 1010 1015 1020 Asn Lys Ser Ala Ser Ala Gly Ile Ile Val Glu Arg Ala Lys Lys Ala 1025 1030 1035 1040 Pro Val Cys Ser Leu Glu Glu Gly Cys Glu Ala Cys Gln 1045 1050 98 1531 PRT Chlamydia trachomatis serovar D 98 Met Ser Ser Glu Lys Asp Ile Lys Ser Thr Cys Ser Lys Phe Ser Leu 5 10 15 Ser Val Val Ala Ala Ile Leu Ala Ser Val Ser Gly Leu Ala Ser Cys 20 25 30 Val Asp Leu His Ala Gly Gly Gln Ser Val Asn Glu Leu Val Tyr Val 35 40 45 Gly Pro Gln Ala Val Leu Leu Leu Asp Gln Ile Arg Asp Leu Phe Val 50 55 60 Gly Ser Lys Asp Ser Gln Ala Glu Gly Gln Tyr Arg Leu Ile Val Gly 65 70 75 80 Asp Pro Ser Ser Phe Gln Glu Lys Asp Ala Asp Thr Leu Pro Gly Lys 85 90 95 Val Glu Gln Ser Thr Leu Phe Ser Val Thr Asn Pro Val Val Phe Gln 100 105 110 Gly Val Asp Gln Gln Asp Gln Val Ser Ser Gln Gly Leu Ile Cys Ser 115 120 125 Phe Thr Ser Ser Asn Leu Asp Ser Pro Arg Asp Gly Glu Ser Phe Leu 130 135 140 Gly Ile Ala Phe Val Gly Asp Ser Ser Lys Ala Gly Ile Thr Leu Thr 145 150 155 160 Asp Val Lys Ala Ser Leu Ser Gly Ala Ala Leu Tyr Ser Thr Glu Asp 165 170 175 Leu Ile Phe Glu Lys Ile Lys Gly Gly Leu Glu Phe Ala Ser Cys Ser 180 185 190 Ser Leu Glu Gln Gly Gly Ala Cys Ala Ala Gln Ser Ile Leu Ile His 195 200 205 Asp Cys Gln Gly Leu Gln Val Lys His Cys Thr Thr Ala Val Asn Ala 210 215 220 Glu Gly Ser Ser Ala Asn Asp His Leu Gly Phe Gly Gly Gly Ala Phe 225 230 235 240 Phe Val Thr Gly Ser Leu Ser Gly Glu Lys Ser Leu Tyr Met Pro Ala 245 250 255 Gly Asp Met Val Val Ala Asn Cys Asp Gly Ala Ile Ser Phe Glu Gly 260 265 270 Asn Ser Ala Asn Phe Ala Asn Gly Gly Ala Ile Ala Ala Ser Gly Lys 275 280 285 Val Leu Phe Val Ala Asn Asp Lys Lys Thr Ser Phe Ile Glu Asn Arg 290 295 300 Ala Leu Ser Gly Gly Ala Ile Ala Ala Ser Ser Asp Ile Ala Phe Gln 305 310 315 320 Asn Cys Ala Glu Leu Val Phe Lys Gly Asn Cys Ala Ile Gly Thr Glu 325 330 335 Asp Lys Gly Ser Leu Gly Gly Gly Ala Ile Ser Ser Leu Gly Thr Val 340 345 350 Leu Leu Gln Gly Asn His Gly Ile Thr Cys Asp Lys Asn Glu Ser Ala 355 360 365 Ser Gln Gly Gly Ala Ile Phe Gly Lys Asn Cys Gln Ile Ser Asp Asn 370 375 380 Glu Gly Pro Val Val Phe Arg Asp Ser Thr Ala Cys Leu Gly Gly Gly 385 390 395 400 Ala Ile Ala Ala Gln Glu Ile Val Ser Ile Gln Asn Asn Gln Ala Gly 405 410 415 Ile Ser Phe Glu Gly Gly Lys Ala Ser Phe Gly Gly Gly Ile Ala Cys 420 425 430 Gly Ser Phe Ser Ser Ala Gly Gly Ala Ser Val Leu Gly Thr Ile Asp 435 440 445 Ile Ser Lys Asn Leu Gly Ala Ile Ser Phe Ser Arg Thr Leu Cys Thr 450 455 460 Thr Ser Asp Leu Gly Gln Met Glu Tyr Gln Gly Gly Gly Ala Leu Phe 465 470 475 480 Gly Glu Asn Ile Ser Leu Ser Glu Asn Ala Gly Val Leu Thr Phe Lys 485 490 495 Asp Asn Ile Val Lys Thr Phe Ala Ser Asn Gly Lys Ile Leu Gly Gly 500 505 510 Gly Ala Ile Leu Ala Thr Gly Lys Val Glu Ile Thr Asn Asn Ser Glu 515 520 525 Gly Ile Ser Phe Thr Gly Asn Ala Arg Ala Pro Gln Ala Leu Pro Thr 530 535 540 Gln Glu Glu Phe Pro Leu Phe Ser Lys Lys Glu Gly Arg Pro Leu Ser 545 550 555 560 Ser Gly Tyr Ser Gly Gly Gly Ala Ile Leu Gly Arg Glu Val Ala Ile 565 570 575 Leu His Asn Ala Ala Val Val Phe Glu Gln Asn Arg Leu Gln Cys Ser 580 585 590 Glu Glu Glu Ala Thr Leu Leu Gly Cys Cys Gly Gly Gly Ala Val His 595 600 605 Gly Met Asp Ser Thr Ser Ile Val Gly Asn Ser Ser Val Arg Phe Gly 610 615 620 Asn Asn Tyr Ala Met Gly Gln Gly Val Ser Gly Gly Ala Leu Leu Ser 625 630 635 640 Lys Thr Val Gln Leu Ala Gly Asn Gly Ser Val Asp Phe Ser Arg Asn 645 650 655 Ile Ala Ser Leu Gly Gly Gly Ala Leu Gln Ala Ser Glu Gly Asn Cys 660 665 670 Glu Leu Val Asp Asn Gly Tyr Val Leu Phe Arg Asp Asn Arg Gly Arg 675 680 685 Val Tyr Gly Gly Ala Ile Ser Cys Leu Arg Gly Asp Val Val Ile Ser 690 695 700 Gly Asn Lys Gly Arg Val Glu Phe Lys Asp Asn Ile Ala Thr Arg Leu 705 710 715 720 Tyr Val Glu Glu Thr Val Glu Lys Val Glu Glu Val Glu Pro Ala Pro 725 730 735 Glu Gln Lys Asp Asn Asn Glu Leu Ser Phe Leu Gly Arg Ala Glu Gln 740 745 750 Ser Phe Ile Thr Ala Ala Asn Gln Ala Leu Phe Ala Ser Glu Asp Gly 755 760 765 Asp Leu Ser Pro Glu Ser Ser Ile Ser Ser Glu Glu Leu Ala Lys Arg 770 775 780 Arg Glu Cys Ala Gly Gly Ala Ile Phe Ala Lys Arg Val Arg Ile Val 785 790 795 800 Asp Asn Gln Glu Ala Val Val Phe Ser Asn Asn Phe Ser Asp Ile Tyr 805 810 815 Gly Gly Ala Ile Phe Thr Gly Ser Leu Arg Glu Glu Asp Lys Leu Asp 820 825 830 Gly Gln Ile Pro Glu Val Leu Ile Ser Gly Asn Ala Gly Asp Val Val 835 840 845 Phe Ser Gly Asn Ser Ser Lys Arg Asp Glu His Leu Pro His Thr Gly 850 855 860 Gly Gly Ala Ile Cys Thr Gln Asn Leu Thr Ile Ser Gln Asn Thr Gly 865 870 875 880 Asn Val Leu Phe Tyr Asn Asn Val Ala Cys Ser Gly Gly Ala Val Arg 885 890 895 Ile Glu Asp His Gly Asn Val Leu Leu Glu Ala Phe Gly Gly Asp Ile 900 905 910 Val Phe Lys Gly Asn Ser Ser Phe Arg Ala Gln Gly Ser Asp Ala Ile 915 920 925 Tyr Phe Ala Gly Lys Glu Ser His Ile Thr Ala Leu Asn Ala Thr Glu 930 935 940 Gly His Ala Ile Val Phe His Asp Ala Leu Val Phe Glu Asn Leu Glu 945 950 955 960 Glu Arg Lys Ser Ala Glu Val Leu Leu Ile Asn Ser Arg Glu Asn Pro 965 970 975 Gly Tyr Thr Gly Ser Ile Arg Phe Leu Glu Ala Glu Ser Lys Val Pro 980 985 990 Gln Cys Ile His Val Gln Gln Gly Ser Leu Glu Leu Leu Asn Gly Ala 995 1000 1005 Thr Leu Cys Ser Tyr Gly Phe Lys Gln Asp Ala Gly Ala Lys Leu Val 1010 1015 1020 Leu Ala Ala Gly Ala Lys Leu Lys Ile Leu Asp Ser Gly Thr Pro Val 1025 1030 1035 1040 Gln Gln Gly His Ala Ile Ser Lys Pro Glu Ala Glu Ile Glu Ser Ser 1045 1050 1055 Ser Glu Pro Glu Gly Ala His Ser Leu Trp Ile Ala Lys Asn Ala Gln 1060 1065 1070 Thr Thr Val Pro Met Val Asp Ile His Thr Ile Ser Val Asp Leu Ala 1075 1080 1085 Ser Phe Ser Ser Ser Gln Gln Glu Gly Thr Val Glu Ala Pro Gln Val 1090 1095 1100 Ile Val Pro Gly Gly Ser Tyr Val Arg Ser Gly Glu Leu Asn Leu Glu 1105 1110 1115 1120 Leu Val Asn Thr Thr Gly Thr Gly Tyr Glu Asn His Ala Leu Leu Lys 1125 1130 1135 Asn Glu Ala Lys Val Pro Leu Met Ser Phe Val Ala Ser Gly Asp Glu 1140 1145 1150 Ala Ser Ala Glu Ile Ser Asn Leu Ser Val Ser Asp Leu Gln Ile His 1155 1160 1165 Val Val Thr Pro Glu Ile Glu Glu Asp Thr Tyr Gly His Met Gly Asp 1170 1175 1180 Trp Ser Glu Ala Lys Ile Gln Asp Gly Thr Leu Val Ile Ser Trp Asn 1185 1190 1195 1200 Pro Thr Gly Tyr Arg Leu Asp Pro Gln Lys Ala Gly Ala Leu Val Phe 1205 1210 1215 Asn Ala Leu Trp Glu Glu Gly Ala Val Leu Ser Ala Leu Lys Asn Ala 1220 1225 1230 Arg Phe Ala His Asn Leu Thr Ala Gln Arg Met Glu Phe Asp Tyr Ser 1235 1240 1245 Thr Asn Val Trp Gly Phe Ala Phe Gly Gly Phe Arg Thr Leu Ser Ala 1250 1255 1260 Glu Asn Leu Val Ala Ile Asp Gly Tyr Lys Gly Ala Tyr Gly Gly Ala 1265 1270 1275 1280 Ser Ala Gly Val Asp Ile Gln Leu Met Glu Asp Phe Val Leu Gly Val 1285 1290 1295 Ser Gly Ala Ala Phe Leu Gly Lys Met Asp Ser Gln Lys Phe Asp Ala 1300 1305 1310 Glu Val Ser Arg Lys Gly Val Val Gly Ser Val Tyr Thr Gly Phe Leu 1315 1320 1325 Ala Gly Ser Trp Phe Phe Lys Gly Gln Tyr Ser Leu Gly Glu Thr Gln 1330 1335 1340 Asn Asp Met Lys Thr Arg Tyr Gly Val Leu Gly Glu Ser Ser Ala Ser 1345 1350 1355 1360 Trp Thr Ser Arg Gly Val Leu Ala Asp Ala Leu Val Glu Tyr Arg Ser 1365 1370 1375 Leu Val Gly Pro Val Arg Pro Thr Phe Tyr Ala Leu His Phe Asn Pro 1380 1385 1390 Tyr Val Glu Val Ser Tyr Ala Ser Met Lys Phe Pro Gly Phe Thr Glu 1395 1400 1405 Gln Gly Arg Glu Ala Arg Ser Phe Glu Asp Ala Ser Leu Thr Asn Ile 1410 1415 1420 Thr Ile Pro Leu Gly Met Lys Phe Glu Leu Ala Phe Ile Lys Gly Gln 1425 1430 1435 1440 Phe Ser Glu Val Asn Ser Leu Gly Ile Ser Tyr Ala Trp Glu Ala Tyr 1445 1450 1455 Arg Lys Val Glu Gly Gly Ala Val Gln Leu Leu Glu Ala Gly Phe Asp 1460 1465 1470 Trp Glu Gly Ala Pro Met Asp Leu Pro Arg Gln Glu Leu Arg Val Ala 1475 1480 1485 Leu Glu Asn Asn Thr Glu Trp Ser Ser Tyr Phe Ser Thr Val Leu Gly 1490 1495 1500 Leu Thr Ala Phe Cys Gly Gly Phe Thr Ser Thr Asp Ser Lys Leu Gly 1505 1510 1515 1520 Tyr Glu Ala Asn Thr Gly Leu Arg Leu Ile Phe 1525 1530 99 474 PRT Chlamydia trachomatis serovar D 99 Met Lys Ile Ile His Thr Ala Ile Glu Phe Ala Pro Val Ile Lys Ala 5 10 15 Gly Gly Leu Gly Asp Ala Leu Tyr Gly Leu Ala Lys Ala Leu Ala Ala 20 25 30 Asn His Thr Thr Glu Val Val Ile Pro Leu Tyr Pro Lys Leu Phe Thr 35 40 45 Leu Pro Lys Glu Gln Asp Leu Cys Ser Ile Gln Lys Leu Ser Tyr Phe 50 55 60 Phe Ala Gly Glu Gln Glu Ala Thr Ala Phe Ser Tyr Phe Tyr Glu Gly 65 70 75 80 Ile Lys Val Thr Leu Phe Lys Leu Asp Thr Gln Pro Glu Leu Phe Glu 85 90 95 Asn Ala Glu Thr Ile Tyr Thr Ser Asp Asp Ala Phe Arg Phe Cys Ala 100 105 110 Phe Ser Ala Ala Ala Ala Ser Tyr Ile Gln Lys Glu Gly Ala Asn Ile 115 120 125 Val His Leu His Asp Trp His Thr Gly Leu Val Ala Gly Leu Leu Lys 130 135 140 Gln Gln Pro Cys Ser Gln Leu Gln Lys Ile Val Leu Thr Leu His Asn 145 150 155 160 Phe Gly Tyr Arg Gly Tyr Thr Thr Arg Glu Ile Leu Glu Ala Ser Ser 165 170 175 Leu Asn Glu Phe Tyr Ile Ser Gln Tyr Gln Leu Phe Arg Asp Pro Gln 180 185 190 Thr Cys Val Leu Leu Lys Gly Ala Leu Tyr Cys Ser Asp Phe Val Thr 195 200 205 Thr Val Ser Pro Thr Tyr Ala Lys Glu Ile Leu Glu Asp Tyr Ser Asp 210 215 220 Tyr Glu Ile His Asp Ala Ile Thr Ala Arg Gln His His Leu Arg Gly 225 230 235 240 Ile Leu Asn Gly Ile Asp Thr Thr Ile Trp Gly Pro Glu Thr Asp Pro 245 250 255 Asn Leu Ala Lys Asn Tyr Thr Lys Glu Leu Phe Glu Thr Pro Ser Ile 260 265 270 Phe Phe Glu Ala Lys Ala Glu Asn Lys Lys Ala Leu Tyr Glu Arg Leu 275 280 285 Gly Leu Ser Leu Glu His Ser Pro Cys Val Cys Ile Ile Ser Arg Ile 290 295 300 Ala Glu Gln Lys Gly Pro His Phe Met Lys Gln Ala Ile Leu His Ala 305 310 315 320 Leu Glu Asn Ala Tyr Thr Leu Ile Ile Ile Gly Thr Cys Tyr Gly Asn 325 330 335 Gln Leu His Glu Glu Phe Ala Asn Leu Gln Glu Ser Leu Ala Asn Ser 340 345 350 Pro Asp Val Arg Ile Leu Leu Thr Tyr Ser Asp Val Leu Ala Arg Gln 355 360 365 Ile Phe Ala Ala Ala Asp Met Ile Cys Ile Pro Ser Met Phe Glu Pro 370 375 380 Cys Gly Leu Thr Gln Met Ile Gly Met Arg Tyr Gly Thr Val Pro Leu 385 390 395 400 Val Arg Ala Thr Gly Gly Leu Ala Asp Thr Val Ala Asn Gly Ile Asn 405 410 415 Gly Phe Ser Phe Phe Asn Pro His Asp Phe Tyr Glu Phe Arg Asn Met 420 425 430 Leu Ser Glu Ala Val Thr Thr Tyr Arg Thr Asn His Asp Lys Trp Gln 435 440 445 His Ile Val Arg Ala Cys Leu Asp Phe Ser Ser Asp Leu Glu Thr Ala 450 455 460 Ala Asn Lys Tyr Leu Glu Ile Tyr Lys Gln 465 470 100 393 PRT Chlamydia trachomatis serovar D 100 Met Lys Lys Leu Leu Lys Ser Val Leu Val Phe Ala Ala Leu Ser Ser 5 10 15 Ala Ser Ser Leu Gln Ala Leu Pro Val Gly Asn Pro Ala Glu Pro Ser 20 25 30 Leu Met Ile Asp Gly Ile Leu Trp Glu Gly Phe Gly Gly Asp Pro Cys 35 40 45 Asp Pro Cys Ala Thr Trp Cys Asp Ala Ile Ser Met Arg Val Gly Tyr 50 55 60 Tyr Gly Asp Phe Val Phe Asp Arg Val Leu Lys Thr Asp Val Asn Lys 65 70 75 80 Glu Phe Gln Met Gly Ala Lys Pro Thr Thr Asp Thr Gly Asn Ser Ala 85 90 95 Ala Pro Ser Thr Leu Thr Ala Arg Glu Asn Pro Ala Tyr Gly Arg His 100 105 110 Met Gln Asp Ala Glu Met Phe Thr Asn Ala Ala Cys Met Ala Leu Asn 115 120 125 Ile Trp Asp Arg Phe Asp Val Phe Cys Thr Leu Gly Ala Thr Ser Gly 130 135 140 Tyr Leu Lys Gly Asn Ser Ala Ser Phe Asn Leu Val Gly Leu Phe Gly 145 150 155 160 Asp Asn Glu Asn Gln Lys Thr Val Lys Ala Glu Ser Val Pro Asn Met 165 170 175 Ser Phe Asp Gln Ser Val Val Glu Leu Tyr Thr Asp Thr Thr Phe Ala 180 185 190 Trp Ser Val Gly Ala Arg Ala Ala Leu Trp Glu Cys Gly Cys Ala Thr 195 200 205 Leu Gly Ala Ser Phe Gln Tyr Ala Gln Ser Lys Pro Lys Val Glu Glu 210 215 220 Leu Asn Val Leu Cys Asn Ala Ala Glu Phe Thr Ile Asn Lys Pro Lys 225 230 235 240 Gly Tyr Val Gly Lys Glu Phe Pro Leu Asp Leu Thr Ala Gly Thr Asp 245 250 255 Ala Ala Thr Gly Thr Lys Asp Ala Ser Ile Asp Tyr His Glu Trp Gln 260 265 270 Ala Ser Leu Ala Leu Ser Tyr Arg Leu Asn Met Phe Thr Pro Tyr Ile 275 280 285 Gly Val Lys Trp Ser Arg Ala Ser Phe Asp Ala Asp Thr Ile Arg Ile 290 295 300 Ala Gln Pro Lys Ser Ala Thr Ala Ile Phe Asp Thr Thr Thr Leu Asn 305 310 315 320 Pro Thr Ile Ala Gly Ala Gly Asp Val Lys Thr Gly Ala Glu Gly Gln 325 330 335 Leu Gly Asp Thr Met Gln Ile Val Ser Leu Gln Leu Asn Lys Met Lys 340 345 350 Ser Arg Lys Ser Cys Gly Ile Ala Val Gly Thr Thr Ile Val Asp Ala 355 360 365 Asp Lys Tyr Ala Val Thr Val Glu Thr Arg Leu Ile Asp Glu Arg Ala 370 375 380 Ala His Val Asn Ala Gln Phe Arg Phe 385 390 101 195 PRT Chlamydia trachomatis serovar D 101 Met Gly Ser Leu Val Gly Arg Gln Ala Pro Asp Phe Ser Gly Lys Ala 5 10 15 Val Val Cys Gly Glu Glu Lys Glu Ile Ser Leu Ala Asp Phe Arg Gly 20 25 30 Lys Tyr Val Val Leu Phe Phe Tyr Pro Lys Asp Phe Thr Tyr Val Cys 35 40 45 Pro Thr Glu Leu His Ala Phe Gln Asp Arg Leu Val Asp Phe Glu Glu 50 55 60 Arg Gly Ala Val Val Leu Gly Cys Ser Val Asp Asp Ile Glu Thr His 65 70 75 80 Ser Arg Trp Leu Ala Val Ala Arg Asn Ala Gly Gly Ile Glu Gly Thr 85 90 95 Glu Tyr Pro Leu Leu Ala Asp Pro Ser Phe Lys Ile Ser Glu Ala Phe 100 105 110 Gly Val Leu Asn Pro Glu Gly Ser Leu Ala Leu Arg Ala Thr Phe Leu 115 120 125 Ile Asp Lys Tyr Gly Val Val Arg His Ala Val Ile Asn Asp Leu Pro 130 135 140 Leu Gly Arg Ser Ile Asp Glu Glu Leu Arg Ile Leu Asp Ser Leu Ile 145 150 155 160 Phe Phe Glu Asn His Gly Met Val Cys Pro Ala Asn Trp Arg Ser Gly 165 170 175 Glu Arg Gly Met Val Pro Ser Glu Glu Gly Leu Lys Glu Tyr Phe Gln 180 185 190 Thr Met Asp 195 102 86 PRT Chlamydia trachomatis serovar D 102 Met Ser Gln Asn Lys Asn Ser Ala Phe Met Gln Pro Val Asn Val Ser 5 10 15 Ala Asp Leu Ala Ala Ile Val Gly Ala Gly Pro Met Pro Arg Thr Glu 20 25 30 Ile Ile Lys Lys Met Trp Asp Tyr Ile Lys Lys Asn Gly Leu Gln Asp 35 40 45 Pro Thr Asn Lys Arg Asn Ile Asn Pro Asp Asp Lys Leu Ala Lys Val 50 55 60 Phe Gly Thr Glu Lys Pro Ile Asp Met Phe Gln Met Thr Lys Met Val 65 70 75 80 Ser Gln His Ile Ile Lys 85 103 394 PRT Chlamydia trachomatis serovar D 103 Met Ser Lys Glu Thr Phe Gln Arg Asn Lys Pro His Ile Asn Ile Gly 5 10 15 Thr Ile Gly His Val Asp His Gly Lys Thr Thr Leu Thr Ala Ala Ile 20 25 30 Thr Arg Ala Leu Ser Gly Asp Gly Leu Ala Asp Phe Arg Asp Tyr Ser 35 40 45 Ser Ile Asp Asn Thr Pro Glu Glu Lys Ala Arg Gly Ile Thr Ile Asn 50 55 60 Ala Ser His Val Glu Tyr Glu Thr Ala Asn Arg His Tyr Ala His Val 65 70 75 80 Asp Cys Pro Gly His Ala Asp Tyr Val Lys Asn Met Ile Thr Gly Ala 85 90 95 Ala Gln Met Asp Gly Ala Ile Leu Val Val Ser Ala Thr Asp Gly Ala 100 105 110 Met Pro Gln Thr Lys Glu His Ile Leu Leu Ala Arg Gln Val Gly Val 115 120 125 Pro Tyr Ile Val Val Phe Leu Asn Lys Ile Asp Met Ile Ser Glu Glu 130 135 140 Asp Ala Glu Leu Val Asp Leu Val Glu Met Glu Leu Val Glu Leu Leu 145 150 155 160 Glu Glu Lys Gly Tyr Lys Gly Cys Pro Ile Ile Arg Gly Ser Ala Leu 165 170 175 Lys Ala Leu Glu Gly Asp Ala Ala Tyr Ile Glu Lys Val Arg Glu Leu 180 185 190 Met Gln Ala Val Asp Asp Asn Ile Pro Thr Pro Glu Arg Glu Ile Asp 195 200 205 Lys Pro Phe Leu Met Pro Ile Glu Asp Val Phe Ser Ile Ser Gly Arg 210 215 220 Gly Thr Val Val Thr Gly Arg Ile Glu Arg Gly Ile Val Lys Val Ser 225 230 235 240 Asp Lys Val Gln Leu Val Gly Leu Arg Asp Thr Lys Glu Thr Ile Val 245 250 255 Thr Gly Val Glu Met Phe Arg Lys Glu Leu Pro Glu Gly Arg Ala Gly 260 265 270 Glu Asn Val Gly Leu Leu Leu Arg Gly Ile Gly Lys Asn Asp Val Glu 275 280 285 Arg Gly Met Val Val Cys Leu Pro Asn Ser Val Lys Pro His Thr Gln 290 295 300 Phe Lys Cys Ala Val Tyr Val Leu Gln Lys Glu Glu Gly Gly Arg His 305 310 315 320 Lys Pro Phe Phe Thr Gly Tyr Arg Pro Gln Phe Phe Phe Arg Thr Thr 325 330 335 Asp Val Thr Gly Val Val Thr Leu Pro Glu Gly Ile Glu Met Val Met 340 345 350 Pro Gly Asp Asn Val Glu Phe Glu Val Gln Leu Ile Ser Pro Val Ala 355 360 365 Leu Glu Glu Gly Met Arg Phe Ala Ile Arg Glu Gly Gly Arg Thr Ile 370 375 380 Gly Ala Gly Thr Ile Ser Lys Ile Ile Ala 385 390 104 82 PRT Chlamydia trachomatis serovar D 104 Met Gly Gln Asp His Arg Arg Lys Phe Leu Lys Lys Val Ser Phe Val 5 10 15 Lys Lys Gln Ala Ala Phe Ala Gly Asn Phe Ile Glu Glu Ile Lys Lys 20 25 30 Ile Glu Trp Val Asn Lys Arg Asp Leu Lys Arg Tyr Val Lys Ile Val 35 40 45 Leu Met Asn Ile Phe Gly Phe Gly Phe Ser Ile Tyr Cys Val Asp Leu 50 55 60 Ala Leu Arg Lys Ser Leu Ser Leu Phe Gly Lys Val Thr Ser Phe Phe 65 70 75 80 Phe Gly 105 379 PRT Chlamydia trachomatis serovar D 105 Met Val Ile Pro Lys Val Asp Leu Gly Glu Ser Ala Val Met Met Gly 5 10 15 Tyr Lys Leu Thr Ser Gln Leu Ala Met Leu Ser Ile Leu Leu Thr Phe 20 25 30 Thr His Thr Met Gly His Ala Ser Gln Met Ser Gln Thr Leu Pro Thr 35 40 45 Ile Ile Glu Ala Gln Ala Glu Glu Ala Leu Gln Ala Asp Arg Gly Val 50 55 60 Ala Gly Gln Ala Leu Lys Lys Leu Arg Lys Lys Arg Cys Ala Ser Arg 65 70 75 80 Lys Ser Ala Cys Lys Ala Ser Phe Lys Lys Lys Asp Phe Phe Ser Cys 85 90 95 Ile Thr Asn Gly Leu Phe Ser Gly Asn His Glu Gln Arg Leu Thr Ala 100 105 110 Lys Lys Glu Asn Lys Ala Arg Gly Lys Glu Pro Arg Val Val Val Gln 115 120 125 Thr Thr Lys Lys Arg Gln Ile Thr Gln Ser Glu Lys Glu Phe Phe Asp 130 135 140 Trp Leu Cys Asn Ser Lys Arg Glu Arg Lys Leu Leu Lys Lys Lys Pro 145 150 155 160 Val Asn Thr Ser Leu Ala Lys Ser Glu Glu Leu Ser Pro Lys Glu Ala 165 170 175 Ala Ile Ala Ala Ala Arg Ala Ser Leu Ser Pro Glu Glu Lys Arg Gln 180 185 190 Leu Ile Arg Glu Trp Leu Ala Glu Glu Lys Thr Ala Arg Lys Ser Gly 195 200 205 Arg Ala Ala Cys Ala Val Ser Glu Asn Leu Lys Arg Asp Gly Ser Ile 210 215 220 Thr Ser Thr Leu Arg Tyr Asp Ala Glu Lys Ala Leu Thr Thr Arg Val 225 230 235 240 Lys Arg Asn Glu Asn Ser Val Asn Ala Arg Ala Arg Gln Arg Ala Ala 245 250 255 Leu Gln Lys Ala Lys Lys Ala Lys Thr Glu Lys Pro Glu Ala Asp Glu 260 265 270 Lys Ala Ala Glu Ala Val Ala Ala Ala Pro Thr Lys Gln Ala His Lys 275 280 285 Glu Pro Glu Asn Tyr Phe Ala Ala Thr Ala Ser Thr Asn Asn Thr Asn 290 295 300 Val Met Ser Tyr Leu Asn Ala His Gln Tyr Arg Cys Asp Ser Ser Glu 305 310 315 320 Thr Asp Trp Pro Cys Ser Ser Cys Val Thr Lys Arg Arg Ala Asn Phe 325 330 335 Gly Ile Ser Val Cys Thr Met Val Val Thr Val Ile Ala Met Ile Val 340 345 350 Gly Ala Val Ile Ile Ser Asn Ala Thr Asp Ser Thr Val Ala Gly Ser 355 360 365 Ser Gly Thr Gly Gly Gly Gly Ser Thr Gln Pro 370 375 106 563 PRT Chlamydia trachomatis serovar D 106 Met Val Tyr Phe Arg Ala His Gln Pro Arg His Thr Pro Lys Thr Phe 5 10 15 Pro Leu Glu Val His His Ser Phe Ser Asp Lys His Pro Gln Ile Ala 20 25 30 Lys Ala Met Arg Ile Thr Gly Ile Ala Leu Ala Ala Leu Ser Leu Leu 35 40 45 Ala Val Val Ala Cys Val Ile Ala Val Ser Ala Gly Gly Ala Ala Ile 50 55 60 Pro Leu Ala Val Ile Ser Gly Ile Ala Val Met Ser Gly Leu Leu Ser 65 70 75 80 Ala Ala Thr Ile Ile Cys Ser Ala Lys Lys Ala Leu Ala Gln Arg Lys 85 90 95 Gln Lys Gln Leu Glu Glu Ser Leu Pro Leu Asp Asn Ala Thr Glu His 100 105 110 Val Ser Tyr Leu Thr Ser Asp Thr Ser Tyr Phe Asn Gln Trp Glu Ser 115 120 125 Leu Gly Ala Leu Asn Lys Gln Leu Ser Gln Ile Asp Leu Thr Ile Gln 130 135 140 Ala Pro Glu Lys Lys Leu Leu Lys Glu Val Leu Gly Ser Arg Tyr Asp 145 150 155 160 Ser Ile Asn His Ser Ile Glu Glu Ile Ser Asp Arg Phe Thr Lys Met 165 170 175 Leu Ser Leu Leu Arg Leu Arg Glu His Phe Tyr Arg Gly Glu Glu Arg 180 185 190 Tyr Ala Pro Tyr Leu Ser Pro Pro Leu Leu Asn Lys Asn Arg Leu Leu 195 200 205 Thr Gln Ile Thr Ser Asn Met Ile Arg Met Leu Pro Lys Ser Gly Gly 210 215 220 Val Phe Ser Leu Lys Ala Asn Thr Leu Ser His Ala Ser Arg Thr Leu 225 230 235 240 Tyr Thr Val Leu Lys Val Ala Leu Ser Leu Gly Val Leu Ala Gly Val 245 250 255 Ala Ala Leu Ile Ile Phe Leu Pro Pro Ser Leu Pro Phe Ile Ala Val 260 265 270 Ile Gly Val Ser Ser Leu Ala Leu Gly Met Ala Ser Phe Leu Met Ile 275 280 285 Arg Gly Ile Lys Tyr Leu Leu Glu His Ser Pro Leu Asn Arg Lys Gln 290 295 300 Leu Ala Lys Asp Ile Gln Lys Thr Ile Gly Pro Asp Val Leu Ala Ser 305 310 315 320 Met Val His Tyr Gln His Gln Leu Leu Ser His Leu His Glu Thr Leu 325 330 335 Leu Asp Glu Ala Ile Thr Ala Arg Trp Ser Glu Pro Phe Phe Ile Glu 340 345 350 His Ala Asn Leu Lys Ala Lys Ile Glu Asp Leu Thr Lys Gln Tyr Asp 355 360 365 Ile Leu Asn Ala Ala Phe Asn Lys Ser Leu Gln Gln Asp Glu Ala Leu 370 375 380 Arg Ser Gln Leu Glu Lys Arg Ala Tyr Leu Phe Pro Ile Pro Asn Asn 385 390 395 400 Asp Glu Asn Ala Lys Thr Lys Glu Ser Gln Leu Leu Asp Ser Glu Asn 405 410 415 Asp Ser Asn Ser Glu Phe Gln Glu Ile Ile Asn Lys Gly Leu Glu Ala 420 425 430 Ala Asn Lys Arg Arg Ala Asp Ala Lys Ser Lys Phe Tyr Thr Glu Asp 435 440 445 Glu Thr Ser Asp Lys Ile Phe Ser Ile Trp Lys Pro Thr Lys Asn Leu 450 455 460 Ala Leu Glu Asp Leu Trp Arg Val His Glu Ala Cys Asn Glu Glu Gln 465 470 475 480 Gln Ala Leu Leu Leu Glu Asp Tyr Met Ser Tyr Lys Thr Ser Glu Cys 485 490 495 Gln Ala Ala Leu Gln Lys Val Ser Gln Glu Leu Lys Ala Ala Gln Lys 500 505 510 Ser Phe Ala Val Leu Glu Lys His Ala Leu Asp Arg Ser Tyr Glu Ser 515 520 525 Ser Val Ala Thr Met Asp Leu Ala Arg Ala Asn Gln Glu Thr His Arg 530 535 540 Leu Leu Asn Ile Leu Ser Glu Leu Gln Gln Leu Ala Gln Tyr Leu Leu 545 550 555 560 Asp Asn His 107 358 PRT Chlamydia trachomatis serovar D 107 Met Arg Lys Thr Val Ile Val Ala Met Ser Gly Gly Val Asp Ser Ser 5 10 15 Val Val Ala Tyr Leu Leu Lys Lys Gln Gly Glu Tyr Asn Val Val Gly 20 25 30 Leu Phe Met Lys Asn Trp Gly Glu Gln Asp Glu Asn Gly Glu Cys Thr 35 40 45 Ala Thr Lys Asp Phe Arg Asp Val Glu Arg Ile Ala Glu Gln Leu Ser 50 55 60 Ile Pro Tyr Tyr Thr Val Ser Phe Ser Lys Glu Tyr Lys Glu Arg Val 65 70 75 80 Phe Ser Arg Phe Leu Arg Glu Tyr Ala Asn Gly Tyr Thr Pro Asn Pro 85 90 95 Asp Val Leu Cys Asn Arg Glu Ile Lys Phe Asp Leu Leu Gln Lys Lys 100 105 110 Val Arg Glu Leu Lys Gly Asp Phe Leu Ala Thr Gly His Tyr Cys Arg 115 120 125 Gly Gly Ala Asp Gly Thr Gly Leu Ser Arg Gly Ile Asp Pro Asn Lys 130 135 140 Asp Gln Ser Tyr Phe Leu Cys Gly Thr Pro Lys Asp Ala Leu Ser Asn 145 150 155 160 Val Leu Phe Pro Leu Gly Gly Met Tyr Lys Thr Glu Val Arg Arg Ile 165 170 175 Ala Gln Glu Ala Gly Leu Ala Thr Ala Thr Lys Lys Asp Ser Thr Gly 180 185 190 Ile Cys Phe Ile Gly Lys Arg Pro Phe Lys Ser Phe Leu Glu Gln Phe 195 200 205 Val Ala Asp Ser Pro Gly Asp Ile Ile Asp Phe Asp Thr Gln Gln Val 210 215 220 Val Gly Arg His Glu Gly Ala His Tyr Tyr Thr Ile Gly Gln Arg Arg 225 230 235 240 Gly Leu Asn Ile Gly Gly Met Glu Lys Pro Cys Tyr Val Leu Ser Lys 245 250 255 Asn Met Glu Lys Asn Ile Val Tyr Ile Val Arg Gly Glu Asp His Pro 260 265 270 Leu Leu Tyr Arg Gln Glu Leu Leu Ala Lys Glu Leu Asn Trp Phe Val 275 280 285 Pro Leu Gln Glu Pro Met Ile Cys Ser Ala Lys Val Arg Tyr Arg Ser 290 295 300 Pro Asp Glu Lys Cys Ser Val Tyr Pro Leu Glu Asp Gly Thr Val Lys 305 310 315 320 Val Ile Phe Asp Val Pro Val Lys Ala Val Thr Pro Gly Gln Thr Val 325 330 335 Ala Phe Tyr Gln Gly Asp Ile Cys Leu Gly Gly Gly Val Ile Glu Val 340 345 350 Pro Met Ile His Gln Leu 355 108 267 PRT Chlamydia trachomatis serovar D 108 Met Ser Arg Lys Pro Ala Ser Asn Ser Ser Arg Asn Thr Lys Arg Ser 5 10 15 Ser Asp Thr Ser Trp Glu Val Ile Ala Gln Asp Tyr Asn Lys Ala Val 20 25 30 Asp Arg Asp Gly His Phe Tyr His Lys Glu Val Ile Leu Pro Asn Leu 35 40 45 Leu Ser Lys Leu His Ile Ser Arg Ser Ser Ser Leu Val Asp Val Gly 50 55 60 Cys Gly Gln Gly Ile Leu Glu Lys His Leu Pro Lys His Leu Pro Tyr 65 70 75 80 Leu Gly Ile Asp Leu Ser Pro Ser Leu Leu Arg Phe Ala Lys Lys Ser 85 90 95 Ala Ser Ser Lys Ser Arg Arg Phe Leu His His Asp Met Thr Gln Pro 100 105 110 Val Pro Ala Asp His His Glu Gln Phe Ser His Ala Thr Ala Ile Leu 115 120 125 Ser Leu Gln Asn Met Glu Ser Pro Glu Gln Ala Ile Ala His Thr Ala 130 135 140 Asn Leu Leu Ala Pro Gln Gly Arg Leu Phe Ile Val Leu Asn His Pro 145 150 155 160 Cys Phe Arg Ile Pro Arg Leu Ser Ser Trp Leu Tyr Asp Glu Pro Lys 165 170 175 Lys Leu Leu Ser Arg Lys Ile Asp Arg Tyr Leu Ser Pro Val Ala Val 180 185 190 Pro Ile Val Val His Pro Gly Glu Lys His Ser Glu Thr Thr Tyr Ser 195 200 205 Phe His Phe Pro Leu Ser Tyr Trp Val Gln Ala Leu Ser Asn His Asn 210 215 220 Leu Leu Ile Asp Ser Met Glu Glu Trp Ile Ser Pro Lys Lys Ser Ser 225 230 235 240 Gly Lys Arg Ala Arg Ala Glu Asn Leu Cys Arg Lys Glu Phe Pro Leu 245 250 255 Phe Leu Phe Ile Ser Ala Leu Lys Ile Ser Lys 260 265 109 867 PRT Chlamydia trachomatis serovar D 109 Met Glu Lys Phe Ser Asp Ala Val Ser Glu Ala Leu Glu Lys Ala Phe 5 10 15 Glu Leu Ala Lys Asn Ser Lys His Ser Tyr Val Thr Glu Asn His Leu 20 25 30 Leu Lys Ser Leu Leu Gln Asn Pro Gly Ser Leu Phe Cys Leu Val Ile 35 40 45 Lys Asp Val His Gly Asn Leu Gly Leu Leu Thr Ser Ala Val Asp Asp 50 55 60 Ala Leu Arg Arg Glu Pro Thr Val Val Glu Gly Thr Ala Val Ala Ser 65 70 75 80 Pro Ser Pro Ser Leu Gln Gln Leu Leu Leu Asn Ala His Gln Glu Ala 85 90 95 Arg Ser Met Gly Asp Glu Tyr Leu Ser Gly Asp His Leu Leu Leu Ala 100 105 110 Phe Trp Arg Ser Thr Lys Glu Pro Phe Ala Ser Trp Arg Lys Thr Val 115 120 125 Lys Thr Thr Ser Glu Ala Leu Lys Glu Leu Ile Thr Lys Leu Arg Gln 130 135 140 Gly Ser Arg Met Asp Ser Pro Ser Ala Glu Glu Asn Leu Lys Gly Leu 145 150 155 160 Glu Lys Tyr Cys Lys Asn Leu Thr Val Leu Ala Arg Glu Gly Lys Leu 165 170 175 Asp Pro Val Ile Gly Arg Asp Glu Glu Ile Arg Arg Thr Ile Gln Val 180 185 190 Leu Ser Arg Arg Thr Lys Asn Asn Pro Met Leu Ile Gly Glu Pro Gly 195 200 205 Val Gly Lys Thr Ala Ile Ala Glu Gly Leu Ala Leu Arg Ile Val Gln 210 215 220 Gly Asp Val Pro Glu Ser Leu Lys Glu Lys His Leu Tyr Val Leu Asp 225 230 235 240 Met Gly Ala Leu Ile Ala Gly Ala Lys Tyr Arg Gly Glu Phe Glu Glu 245 250 255 Arg Leu Lys Ser Val Leu Lys Gly Val Glu Ala Ser Glu Gly Glu Cys 260 265 270 Ile Leu Phe Ile Asp Glu Val His Thr Leu Val Gly Ala Gly Ala Thr 275 280 285 Asp Gly Ala Met Asp Ala Ala Asn Leu Leu Lys Pro Ala Leu Ala Arg 290 295 300 Gly Thr Leu His Cys Ile Gly Ala Thr Thr Leu Asn Glu Tyr Gln Lys 305 310 315 320 Tyr Ile Glu Lys Asp Ala Ala Leu Glu Arg Arg Phe Gln Pro Ile Phe 325 330 335 Val Thr Glu Pro Ser Leu Glu Asp Ala Val Phe Ile Leu Arg Gly Leu 340 345 350 Arg Glu Lys Tyr Glu Ile Phe His Gly Val Arg Ile Thr Glu Gly Ala 355 360 365 Leu Asn Ala Ala Val Val Leu Ser Tyr Arg Tyr Ile Thr Asp Arg Phe 370 375 380 Leu Pro Asp Lys Ala Ile Asp Leu Ile Asp Glu Ala Ala Ser Leu Ile 385 390 395 400 Arg Met Gln Ile Gly Ser Leu Pro Leu Pro Ile Asp Glu Lys Glu Arg 405 410 415 Glu Leu Ser Ala Leu Ile Val Lys Gln Glu Ala Ile Lys Arg Glu Gln 420 425 430 Ala Pro Ala Tyr Gln Glu Glu Ala Glu Asp Met Gln Lys Ala Ile Asp 435 440 445 Arg Val Lys Glu Glu Leu Ala Ala Leu Arg Leu Arg Trp Asp Glu Glu 450 455 460 Lys Gly Leu Ile Thr Gly Leu Lys Glu Lys Lys Asn Ala Leu Glu Asn 465 470 475 480 Leu Lys Phe Ala Glu Glu Glu Ala Glu Arg Thr Ala Asp Tyr Asn Arg 485 490 495 Val Ala Glu Leu Arg Tyr Ser Leu Ile Pro Ser Leu Glu Glu Glu Ile 500 505 510 His Leu Ala Glu Glu Ala Leu Asn Gln Arg Asp Gly Arg Leu Leu Gln 515 520 525 Glu Glu Val Asp Glu Arg Leu Ile Ala Gln Val Val Ala Asn Trp Thr 530 535 540 Gly Ile Pro Val Gln Lys Met Leu Glu Gly Glu Ser Glu Lys Leu Leu 545 550 555 560 Val Leu Glu Glu Ser Leu Glu Glu Arg Val Val Gly Gln Pro Phe Ala 565 570 575 Ile Ala Ala Val Ser Asp Ser Ile Arg Ala Ala Arg Val Gly Leu Ser 580 585 590 Asp Pro Gln Arg Pro Leu Gly Val Phe Leu Phe Leu Gly Pro Thr Gly 595 600 605 Val Gly Lys Thr Glu Leu Ala Lys Ala Leu Ala Glu Leu Leu Phe Asn 610 615 620 Lys Glu Glu Ala Met Ile Arg Phe Asp Met Thr Glu Tyr Met Glu Lys 625 630 635 640 His Ser Val Ser Lys Leu Ile Gly Ser Pro Pro Gly Tyr Val Gly Tyr 645 650 655 Glu Glu Gly Gly Ser Leu Ser Glu Ala Leu Arg Arg Arg Pro Tyr Ser 660 665 670 Val Val Leu Phe Asp Glu Ile Glu Lys Ala Asp Lys Glu Val Phe Asn 675 680 685 Ile Leu Leu Gln Ile Phe Asp Asp Gly Ile Leu Thr Asp Ser Lys Lys 690 695 700 Arg Lys Val Asn Cys Lys Asn Ala Leu Phe Ile Met Thr Ser Asn Ile 705 710 715 720 Gly Ser Gln Glu Leu Ala Asp Tyr Cys Thr Lys Lys Gly Thr Ile Val 725 730 735 Asp Lys Glu Ala Val Leu Ser Val Val Ala Pro Ala Leu Lys Asn Tyr 740 745 750 Phe Ser Pro Glu Phe Ile Asn Arg Ile Asp Asp Ile Leu Pro Phe Val 755 760 765 Pro Leu Thr Thr Glu Asp Ile Val Lys Ile Val Gly Ile Gln Met Asn 770 775 780 Arg Val Ala Leu Arg Leu Leu Glu Arg Lys Ile Ser Leu Thr Trp Asp 785 790 795 800 Asp Ser Leu Val Leu Phe Leu Ser Glu Gln Gly Tyr Asp Ser Ala Phe 805 810 815 Gly Ala Arg Pro Leu Lys Arg Leu Ile Gln Gln Lys Val Val Thr Met 820 825 830 Leu Ser Lys Ala Leu Leu Lys Gly Asp Ile Lys Pro Gly Met Ala Val 835 840 845 Glu Leu Thr Met Ala Lys Asp Val Val Val Phe Lys Ile Lys Thr Asn 850 855 860 Pro Ala Val 865 110 1170 DNA Chlamydia pneumoniae 110 atgaaaaaac tcttaaagtc ggcgttatta tccgccgcat ttgctggttc tgttggctcc 60 ttacaagcct tgcctgtagg gaacccttct gatccaagct tattaattga tggtacaata 120 tgggaaggtg ctgcaggaga tccttgcgat ccttgcgcta cttggtgcga cgctattagc 180 ttacgtgctg gattttacgg agactatgtt ttcgaccgta tcttaaaagt agatgcacct 240 aaaacatttt ctatgggagc caagcctact ggatccgctg ctgcaaacta tactactgcc 300 gtagatagac ctaacccggc ctacaataag catttacacg atgcagagtg gttcactaat 360 gcaggcttca ttgccttaaa catttgggat cgctttgatg ttttctgtac tttaggagct 420 tctaatggtt acattagagg aaactctaca gcgttcaatc tcgttggttt attcggagtt 480 aaaggtacta ctgtaaatgc aaatgaacta ccaaacgttt ctttaagtaa cggagttgtt 540 gaactttaca cagacacctc tttctcttgg agcgtaggcg ctcgtggagc cttatgggaa 600 tgcggttgtg caactttggg agctgaattc caatatgcac agtccaaacc taaagttgaa 660 gaacttaatg tgatctgtaa cgtatcgcaa ttctctgtaa acaaacccaa gggctataaa 720 ggcgttgctt tccccttgcc aacagacgct ggcgtagcaa cagctactgg aacaaagtct 780 gcgaccatca attatcatga atggcaagta ggagcctctc tatcttacag actaaactct 840 ttagtgccat acattggagt acaatggtct cgagcaactt ttgatgctga taacatccgc 900 attgctcagc caaaactacc tacagctgtt ttaaacttaa ctgcatggaa cccttcttta 960 ctaggaaatg ccacagcatt gtctactact gattcgttct cagacttcat gcaaattgtt 1020 tcctgtcaga tcaacaagtt taaatctaga aaagcttgtg gagttactgt aggagctact 1080 ttagttgatg ctgataaatg gtcacttact gcagaagctc gtttaattaa cgagagagct 1140 gctcacgtat ctggtcagtt cagattctaa 1170 111 2601 DNA Chlamydia pneumoniae 111 atggagaaat tttccgatgc tgtctctgaa gctttagaga aggctttcga acttgctaaa 60 tcttcgaaac atacctatgt cacagaaaat cacctattac tggctttatt agaaaataca 120 gagtctctct tttatttggt aattaaggac attcatggga accctggttt gctcaatacg 180 gcagttaaag atgcgctctc acgagagccg actgtagttg aaggagaggt ggatcctaaa 240 ccttctccgg gtttacaaac ccttcttagg gatgccaaac aagaggcaaa gacattagga 300 gatgaataca tttctggaga tcatctgctg cttgcttttt ggagttcaaa caaagagcct 360 tttaattctt ggaagcaaac aacaaaagtt agttttaaag atcttaagaa tctgattact 420 aaaatacgac gaggaaatcg tatggattcg ccaagcgctg aaagtaattt tcagggttta 480 gaaaagtatt gtaaaaattt aacagcatta gctcgtgaag gtaaactgga tcctgtgatc 540 ggtagagatg aagaaattcg tagaaccatc caagtgcttt cccgtagaac taaaaataac 600 cctatgctta ttggtgagcc gggtgtaggg aaaactgcta tagcagaagg attagctctt 660 aggcttatcc agggtgatgt tcctgaatct ctcaaaggta aacagcttta tgtcttagat 720 atgggagctt tgattgcagg agctaagtat cgaggtgagt ttgaagaaag actaaagagt 780 gttttaaaag atgtagaatc tggagatggc gagcacatta tctttattga tgaggtgcat 840 actcttgttg gagcaggagc tactgatgga gctatggatg ctgcgaatct tttaaagcct 900 gcattagcaa gagggacgct acactgtatt ggcgcgacga ctttgaatga gtatcagaag 960 tatattgaaa aagatgctgc tttggaacgt cgatttcagc ctatttttgt gacagagcct 1020 tctttggagg atgctgtctt tattcttcgt ggactaagag aaaaatatga aattttccat 1080 ggagtcagga ttacagaggg ggctttgaat gccgcagtcc tactttccta tcgttatatc 1140 ccagatcgct ttcttccaga taaggctatc gatttgatag atgaagcggc aagtttaatt 1200 cgcatgcaaa ttggtagtct tcctcttcct attgatgaaa aggagagaga gcttgctgct 1260 ttgatcgtta agcaagaggc tataaaacgc gagcaatctc cttcctatca agaagaggcg 1320 gatgctatgc agaagtctat agatgctttg agagaggaat tagcatctct acgtttgggt 1380 tgggatgaag agaagaagtt gatttcgggg ctcaaggaaa aaaagaattc cttggaaagt 1440 atgaaatttt ctgaagagga ggcggagcgt gttgcagact ataatcgtgt agctgagctt 1500 cggtatagtt taattcccca acttgaagaa gaaatcaaac aggatgaagc ctctttaaat 1560 caaagagata accgtctcct tcaagaagaa gttgacgagc gattgattgc gcaagtggta 1620 gctaattgga cagggattcc tgtgcaaaaa atgctagaag gggaagctga gaaactgtta 1680 attcttgaag aatccttaga agaacgtgtg gtaggacagc cttttgcagt ctctgcggtt 1740 agtgattcta ttcgtgctgc acgtgtaggt ttaaatgatc ctcaacgtcc cttaggagtc 1800 tttttatttt tagggccaac aggggtagga aaaaccgagc ttgcaaaagc tcttgcagat 1860 cttcttttca ataaagagga agctatggtc cgcttcgata tgtcagagta tatggaaaag 1920 cattccattt ccaagcttat aggatcttct ccagggtatg tgggttatga ggaaggtggg 1980 agtctttctg aggctcttcg acgacgtccc tattcagtag ttctctttga tgagatagag 2040 aaagcagata aggaagttct aaatatcctt ttacaggttt ttgatgatgg gattcttacg 2100 gatgggaaaa aacgcaaagt aaattgtaaa aatgccttgt ttatcatgac atcaaatata 2160 ggttctccag aacttgcaga ttattgttca aaaaaaggaa gtgagcttac gaaagaagcg 2220 attctttctg tagtctctcc agtattgaaa agatacttga gccctgaatt tatgaaccga 2280 attgatgaga tacttccttt tgttccatta acgaaagaag atatcgtgaa aatagttggc 2340 attcaaatgc gaaggattgc ccagagatta aaggcacggc ggatcaattt atcttgggat 2400 gattctgtaa tattatttct tagtgaacag ggttatgaca gtgctttcgg agcccgccct 2460 ttaaaacgtt tgatccaaca aaaagttgtg atcttgcttt ctaaggcttt gcttaaagga 2520 gatattaaac ctgatacatc gattgagttg acgatggcaa aagaggtgct cgtatttaaa 2580 aaagtggaaa ctccttctta g 2601 112 389 PRT Chlamydia pneumoniae 112 Met Lys Lys Leu Leu Lys Ser Ala Leu Leu Ser Ala Ala Phe Ala Gly 5 10 15 Ser Val Gly Ser Leu Gln Ala Leu Pro Val Gly Asn Pro Ser Asp Pro 20 25 30 Ser Leu Leu Ile Asp Gly Thr Ile Trp Glu Gly Ala Ala Gly Asp Pro 35 40 45 Cys Asp Pro Cys Ala Thr Trp Cys Asp Ala Ile Ser Leu Arg Ala Gly 50 55 60 Phe Tyr Gly Asp Tyr Val Phe Asp Arg Ile Leu Lys Val Asp Ala Pro 65 70 75 80 Lys Thr Phe Ser Met Gly Ala Lys Pro Thr Gly Ser Ala Ala Ala Asn 85 90 95 Tyr Thr Thr Ala Val Asp Arg Pro Asn Pro Ala Tyr Asn Lys His Leu 100 105 110 His Asp Ala Glu Trp Phe Thr Asn Ala Gly Phe Ile Ala Leu Asn Ile 115 120 125 Trp Asp Arg Phe Asp Val Phe Cys Thr Leu Gly Ala Ser Asn Gly Tyr 130 135 140 Ile Arg Gly Asn Ser Thr Ala Phe Asn Leu Val Gly Leu Phe Gly Val 145 150 155 160 Lys Gly Thr Thr Val Asn Ala Asn Glu Leu Pro Asn Val Ser Leu Ser 165 170 175 Asn Gly Val Val Glu Leu Tyr Thr Asp Thr Ser Phe Ser Trp Ser Val 180 185 190 Gly Ala Arg Gly Ala Leu Trp Glu Cys Gly Cys Ala Thr Leu Gly Ala 195 200 205 Glu Phe Gln Tyr Ala Gln Ser Lys Pro Lys Val Glu Glu Leu Asn Val 210 215 220 Ile Cys Asn Val Ser Gln Phe Ser Val Asn Lys Pro Lys Gly Tyr Lys 225 230 235 240 Gly Val Ala Phe Pro Leu Pro Thr Asp Ala Gly Val Ala Thr Ala Thr 245 250 255 Gly Thr Lys Ser Ala Thr Ile Asn Tyr His Glu Trp Gln Val Gly Ala 260 265 270 Ser Leu Ser Tyr Arg Leu Asn Ser Leu Val Pro Tyr Ile Gly Val Gln 275 280 285 Trp Ser Arg Ala Thr Phe Asp Ala Asp Asn Ile Arg Ile Ala Gln Pro 290 295 300 Lys Leu Pro Thr Ala Val Leu Asn Leu Thr Ala Trp Asn Pro Ser Leu 305 310 315 320 Leu Gly Asn Ala Thr Ala Leu Ser Thr Thr Asp Ser Phe Ser Asp Phe 325 330 335 Met Gln Ile Val Ser Cys Gln Ile Asn Lys Phe Lys Ser Arg Lys Ala 340 345 350 Cys Gly Val Thr Val Gly Ala Thr Leu Val Asp Ala Asp Lys Trp Ser 355 360 365 Leu Thr Ala Glu Ala Arg Leu Ile Asn Glu Arg Ala Ala His Val Ser 370 375 380 Gly Gln Phe Arg Phe 385 113 866 PRT Chlamydia pneumoniae 113 Met Glu Lys Phe Ser Asp Ala Val Ser Glu Ala Leu Glu Lys Ala Phe 5 10 15 Glu Leu Ala Lys Ser Ser Lys His Thr Tyr Val Thr Glu Asn His Leu 20 25 30 Leu Leu Ala Leu Leu Glu Asn Thr Glu Ser Leu Phe Tyr Leu Val Ile 35 40 45 Lys Asp Ile His Gly Asn Pro Gly Leu Leu Asn Thr Ala Val Lys Asp 50 55 60 Ala Leu Ser Arg Glu Pro Thr Val Val Glu Gly Glu Val Asp Pro Lys 65 70 75 80 Pro Ser Pro Gly Leu Gln Thr Leu Leu Arg Asp Ala Lys Gln Glu Ala 85 90 95 Lys Thr Leu Gly Asp Glu Tyr Ile Ser Gly Asp His Leu Leu Leu Ala 100 105 110 Phe Trp Ser Ser Asn Lys Glu Pro Phe Asn Ser Trp Lys Gln Thr Thr 115 120 125 Lys Val Ser Phe Lys Asp Leu Lys Asn Leu Ile Thr Lys Ile Arg Arg 130 135 140 Gly Asn Arg Met Asp Ser Pro Ser Ala Glu Ser Asn Phe Gln Gly Leu 145 150 155 160 Glu Lys Tyr Cys Lys Asn Leu Thr Ala Leu Ala Arg Glu Gly Lys Leu 165 170 175 Asp Pro Val Ile Gly Arg Asp Glu Glu Ile Arg Arg Thr Ile Gln Val 180 185 190 Leu Ser Arg Arg Thr Lys Asn Asn Pro Met Leu Ile Gly Glu Pro Gly 195 200 205 Val Gly Lys Thr Ala Ile Ala Glu Gly Leu Ala Leu Arg Leu Ile Gln 210 215 220 Gly Asp Val Pro Glu Ser Leu Lys Gly Lys Gln Leu Tyr Val Leu Asp 225 230 235 240 Met Gly Ala Leu Ile Ala Gly Ala Lys Tyr Arg Gly Glu Phe Glu Glu 245 250 255 Arg Leu Lys Ser Val Leu Lys Asp Val Glu Ser Gly Asp Gly Glu His 260 265 270 Ile Ile Phe Ile Asp Glu Val His Thr Leu Val Gly Ala Gly Ala Thr 275 280 285 Asp Gly Ala Met Asp Ala Ala Asn Leu Leu Lys Pro Ala Leu Ala Arg 290 295 300 Gly Thr Leu His Cys Ile Gly Ala Thr Thr Leu Asn Glu Tyr Gln Lys 305 310 315 320 Tyr Ile Glu Lys Asp Ala Ala Leu Glu Arg Arg Phe Gln Pro Ile Phe 325 330 335 Val Thr Glu Pro Ser Leu Glu Asp Ala Val Phe Ile Leu Arg Gly Leu 340 345 350 Arg Glu Lys Tyr Glu Ile Phe His Gly Val Arg Ile Thr Glu Gly Ala 355 360 365 Leu Asn Ala Ala Val Leu Leu Ser Tyr Arg Tyr Ile Pro Asp Arg Phe 370 375 380 Leu Pro Asp Lys Ala Ile Asp Leu Ile Asp Glu Ala Ala Ser Leu Ile 385 390 395 400 Arg Met Gln Ile Gly Ser Leu Pro Leu Pro Ile Asp Glu Lys Glu Arg 405 410 415 Glu Leu Ala Ala Leu Ile Val Lys Gln Glu Ala Ile Lys Arg Glu Gln 420 425 430 Ser Pro Ser Tyr Gln Glu Glu Ala Asp Ala Met Gln Lys Ser Ile Asp 435 440 445 Ala Leu Arg Glu Glu Leu Ala Ser Leu Arg Leu Gly Trp Asp Glu Glu 450 455 460 Lys Lys Leu Ile Ser Gly Leu Lys Glu Lys Lys Asn Ser Leu Glu Ser 465 470 475 480 Met Lys Phe Ser Glu Glu Glu Ala Glu Arg Val Ala Asp Tyr Asn Arg 485 490 495 Val Ala Glu Leu Arg Tyr Ser Leu Ile Pro Gln Leu Glu Glu Glu Ile 500 505 510 Lys Gln Asp Glu Ala Ser Leu Asn Gln Arg Asp Asn Arg Leu Leu Gln 515 520 525 Glu Glu Val Asp Glu Arg Leu Ile Ala Gln Val Val Ala Asn Trp Thr 530 535 540 Gly Ile Pro Val Gln Lys Met Leu Glu Gly Glu Ala Glu Lys Leu Leu 545 550 555 560 Ile Leu Glu Glu Ser Leu Glu Glu Arg Val Val Gly Gln Pro Phe Ala 565 570 575 Val Ser Ala Val Ser Asp Ser Ile Arg Ala Ala Arg Val Gly Leu Asn 580 585 590 Asp Pro Gln Arg Pro Leu Gly Val Phe Leu Phe Leu Gly Pro Thr Gly 595 600 605 Val Gly Lys Thr Glu Leu Ala Lys Ala Leu Ala Asp Leu Leu Phe Asn 610 615 620 Lys Glu Glu Ala Met Val Arg Phe Asp Met Ser Glu Tyr Met Glu Lys 625 630 635 640 His Ser Ile Ser Lys Leu Ile Gly Ser Ser Pro Gly Tyr Val Gly Tyr 645 650 655 Glu Glu Gly Gly Ser Leu Ser Glu Ala Leu Arg Arg Arg Pro Tyr Ser 660 665 670 Val Val Leu Phe Asp Glu Ile Glu Lys Ala Asp Lys Glu Val Leu Asn 675 680 685 Ile Leu Leu Gln Val Phe Asp Asp Gly Ile Leu Thr Asp Gly Lys Lys 690 695 700 Arg Lys Val Asn Cys Lys Asn Ala Leu Phe Ile Met Thr Ser Asn Ile 705 710 715 720 Gly Ser Pro Glu Leu Ala Asp Tyr Cys Ser Lys Lys Gly Ser Glu Leu 725 730 735 Thr Lys Glu Ala Ile Leu Ser Val Val Ser Pro Val Leu Lys Arg Tyr 740 745 750 Leu Ser Pro Glu Phe Met Asn Arg Ile Asp Glu Ile Leu Pro Phe Val 755 760 765 Pro Leu Thr Lys Glu Asp Ile Val Lys Ile Val Gly Ile Gln Met Arg 770 775 780 Arg Ile Ala Gln Arg Leu Lys Ala Arg Arg Ile Asn Leu Ser Trp Asp 785 790 795 800 Asp Ser Val Ile Leu Phe Leu Ser Glu Gln Gly Tyr Asp Ser Ala Phe 805 810 815 Gly Ala Arg Pro Leu Lys Arg Leu Ile Gln Gln Lys Val Val Ile Leu 820 825 830 Leu Ser Lys Ala Leu Leu Lys Gly Asp Ile Lys Pro Asp Thr Ser Ile 835 840 845 Glu Leu Thr Met Ala Lys Glu Val Leu Val Phe Lys Lys Val Glu Thr 850 855 860 Pro Ser 865 114 1179 DNA Homo sapiens 114 taactctccc ctctcttctt aaaaaagagg ggagcctttt ttccttacaa agatacgcta 60 gctttttcct gaagaatctc atcaagagat atttgcattt tcccacggat aaaggcatcc 120 caaggaagcc ctggaatcac ttcatattct cccgttgcta gcattcgaca agggaaacca 180 aagattaaat cttccggtaa tccataggga ttgtggtccg aacacactcc ggaagaaaac 240 cattctcctt cttttggctg atatattgat cgagcagcct ctgctaaagc tcgtgctgca 300 gaagctgccg aagacttccc tcgtgcttcg attactgcac taccacgact ctgtacagaa 360 ggcaccataa tattctctaa ccaatcacga tccgctatcg tctctgcgat aggacggtca 420 ttaatcagag cttgcgtaaa atcaggcact tgtttggcgg agtgatttcc ccaaaccaca 480 acttgtgata cagccgataa aggtacttct gctctatgcg ataacatgct atgcatacga 540 ttctggtcca atcgtagcat cgcatgaaag ttctttctca ataatctggg agcatgattc 600 attgctatcc agcaattggt attcacaggg ttcccaacaa caaaaatctt tgcatcccgc 660 ttggctgttg tgttcaaagc ttttccttgc gtagcaaaaa tctccccatt tttctttaga 720 agatcccttc tctccattcc tgggcctcta ggaactgacc ctataaggaa tgccgcatca 780 atgccatcaa aagcatcatg caatgatgtc gttacctgca cacgctgtaa taaagggaaa 840 gcaccatcat ctagctccat gcgcacacca gataaagccc tttctgttcc aggaatatcg 900 tagatacgca gatcgatgcc acaatcaagg ccaaaaacat ctccatgagc cagagaaaat 960 agaaagctat aggctatttg ccctgttcct cctgttactg ctacactcac tgtttgagaa 1020 accataagcc accctctctt tacttttaca aaacgcacat actctcaaca ctacgtttgc 1080 aactaactaa ttttggtccc aacatacgtt tggatgataa aagaatcaag tacctagatt 1140 ccttagtaaa agcttttggc aaaaaaaagc tcatctatt 1179 115 772 DNA Homo sapiens 115 gcaaaactgc tgacaaagct ggagacggaa ctacaacagc tactgttctt gctgaagcta 60 tctatacaga aggattacgc aatgtaacag ctggagcaaa tccaatggac ctcaaacgag 120 gtattgataa agctgttaag gttgttgttg atcaaatcag aaaaatcagc aaacctgttc 180 agcatcataa agaaattgct caagttgcaa caatttctgc taataatgat gcagaaatcg 240 ggaatctgat tgctgaagca atggagaaag ttggtaaaaa cggctctatc actgttgaag 300 aagcaaaagg atttgaaacc gttttggatg ttgttgaagg aatgaatttc aatagaggtt 360 acctctctag ctacttcgca acaaatccag aaactcaaga atgtgtatta gaagacgctt 420 tggttctaat ctacgataag aaaatttctg ggatcaaaga tttccttcct gttttacaac 480 aagttgctga atccggccgt cctcttctta ttatagcaga agacattgaa ggcgaagctt 540 tagctacttt ggtcgtgaac agaattcgtg gaggattccg ggtttgcgca gttaaagctc 600 caggctttgg agatagaaga aaagctatgt tggaagacat cgctatctta actggcggtc 660 aactcattag cgaagagttg ggcatgaaat tagaaaacgc taacttagct atgttaggta 720 aagctaaaaa agttatcgtt tctaaggaag acacgaccat cgtcgaagga at 772 116 487 DNA Homo sapiens 116 gcagctcctg caaagccaca agctcctgtc gcacaaacac ggcattttaa aaagagccat 60 cagattttct ctcctaattt tacgcagtct tcccaacagg tgaataaacc tgaggaaaga 120 agacgtcctt tggagtctcg atacttacaa ggcgcggcta agcaggcagc tgctgcaaag 180 gaaaaaaagg ctcttgaaca ggaagtatcc aaacaagaag aagaagcttc taaactctgg 240 gaagagaaac agagttatgc tcgtcgtgct gtgaatgcca tcaatttcag tgtaagaaag 300 caaatagaag agcaacagaa aaccatttcc aatccaggaa atgaccagac tcttcctggg 360 aagaaagatc cacatacatc cggagaacct gttatccaaa cggtacaaga ctgttctcag 420 gatcaagaag aagagaaaaa agttctagag cgattaaaca aacgttctct gacgtgtcag 480 gatctta 487 117 1014 DNA Homo sapiens 117 ctcgtgccga atcttctaac aagagaacaa gctcctttct ttcttttcta aacaaggttc 60 agcgctttct attaaaagaa accctattca gaccctatgc agcacatagt tttataaaaa 120 atttttctat taacagagga aaaataacct attgataaac agagcggtac aaggagatgc 180 aaataaagct gctttaggat ccttacctag attctagaaa atggttgcat gaatttgaac 240 aaacaaacta attaaaaatt aaaactgaaa aaaatagttt aaaacaacaa ctagaggata 300 ttttttcatg gcgctaaaag atacggcaaa aaaaatgact gacttgttgg aaagtatcca 360 acaaaatttg cttaaagcag aaaaaggaaa taaagccgca gcacaaagag ttcgtacaga 420 atctatcaaa ttagaaaaga tcgcgaaggt atatcgtaaa gagtccatta aagcagaaaa 480 aatgggctta atgaaaaaaa gcaaagccgc tgctaaaaaa gctaaagctg ctgctaagaa 540 gcctgttcgc gctacaaaaa cagtggctaa aaaagcttgt acaaaaagaa cttgtgctac 600 taaagcaaag gtcaaaccaa caaaaaaagc cgctcctaaa acaaaagtta aaacagcgaa 660 aaaaactcgc tcaacaaaaa aataatattt tagcgctttc tcttttttat agagggcact 720 tttatcaaca gggccctctt tcctcttctc attgatccct tctctttttt ttgttatcct 780 ttccgttctc gcaaaggcaa gtccttgcaa ataaaagtac aacctcacac ctcctttgga 840 ggaaaaacct ttcactttct ttaggattca agttgctctc ctgctatcgt aactgtaaac 900 attttggcgt ctgtggaggc tgttcatctc ctcaaatgga atatgcatcc tctttaaaaa 960 caaaagagct tgcgctccat aatttatttg cacctcttat cccatcccaa aata 1014 118 287 DNA Homo sapiens 118 atgcaaataa agctgcttta ggatccttac ctagattcta gaaaatggtt gcatgaattt 60 gaacaaacaa actaattaaa aattaaaact gaaaaaaata gtttaaaaca acaactagag 120 gatatttttt catggcgcta aaagatacgg caaaaaaaat gactgacttg ttggaaagta 180 tccaacaaaa tttgcttaaa gcagaaaaag gaaataaagc cgcagcacaa agagttcgta 240 cagaatctat caaattagaa aagatcgcga aggtatatcg taaagag 287 119 1002 DNA Homo sapiens 119 catatgcatc accatcacca tcacatgagt attcgaccta ctaatgggag tggaaatgga 60 tacccgtcta ttaatccttc taacgataat caatacggtc ttgtgcaatc gacctctggg 120 cctaattacg gaggccatac ggtatcttct cgaggaggat ttcaagggat atgcgtacga 180 atagccgatt tattccgtaa ctgtttctct cgtaatagag gcactactac tacgccatct 240 cgaactgtta tcactcaggc agatatttat catccgacta tttctggaca aggagctcaa 300 cctattgtct ctacaggaga taagaaatta gatagcgcaa ttattcaagc agatttgcgt 360 gcgcagaata aacagacttt ggctacacat attcaaagta agctaggttc tatggaggga 420 caatctcctc aagattataa agctggtgcg tatagtgcgc taagattgat gctgtttact 480 ccaggcgaaa ctactgtgag tagcgagcgg gaacgtcaag cgtgcgttac gggtcgggat 540 ctctgggaac aggctgcagg agatcttgct accaatggga atacagatgg gcttatgtta 600 atggctaacc tatctgtggg agggaagcat gtgcctgcgg ggcatttaag agaatacatg 660 gatactgtaa agggtacgtt tactgatgag aacgaggcta cagatcctac ggtagatgcc 720 attttagatt tagcagcaaa aatcgatgcg acggaattct ctagtcctgg ttcagggcaa 780 gtcattctta attatatagg aaattatgga caagtcgttt tagaaaacga ggagatgaac 840 cttcttgttt tagaagatca aaatgggcaa gatcctcaac gtgttcaaga taactcaaaa 900 gagttacaaa aactgttaga aaatgctcga aaaacagatc ctgagttata tttccaaaca 960 ctaactgtca taacttcttc tgttttctta gactaaggat cc 1002 120 1218 DNA Homo sapiens 120 atgcatcacc atcaccatca cgtgagtagc ataagcccta taggggggaa ttctgggcca 60 gagggatttt ctagtgcatc tcgaggcgat gagattgatg atgtaccaga tagtgaagag 120 ggagagctag aagagcgcgt ttcggatcat gcagagtcta tcattaccga gagctcggaa 180 acgctgtttc gtactacttc ttcatcaggg gtcagtgaag atcttcagca acacgttagc 240 ttggaggaat ctccacgaca acgaggtttc cttggacgga tccgtgatgc agtagcttct 300 atttggaagc gtcgtgttgc acgaaggaat gaaaactatg atgtgaaaaa agcagaagag 360 cagcaaggga ttgtgcaata tctgcaggat tcgaaaatgc ctgctttaac gcgtgcctat 420 cgccatctcc gtgctttcaa ttctgcatgc ttacgtacga ttcgtgagtt tttcgctacc 480 atttttcgtg ctttaaggga tgcgtattat cgacattgta cacgttctgg gatcaacttt 540 tgtggagctg ataaagactc tttagaagtt cttgttgcgg tgggtttgct tttgcgtatg 600 gctaccttac gctcttttga acatgtcggt gggaattacg aagatcgatt agtaaataat 660 gatgctccgg tgacaggtgc ggggagaact cttgttgatg atgctgtaga cgatattgaa 720 tcgattttaa atacgagaac caactggcct caacatgtca tgatagggtt ttctcgtggt 780 ctcgttcaat tatgtgcgac tccttataat gcgacttctc aagaatgttt caagtcgatt 840 gttcgtttag aaaaagaaga cccttcttca gattattctc aagctttatt attagcaggg 900 ataatagatc gcttggcgga gaaagcccct atggctgcaa agtatgtttt ggatgcattg 960 cgtgttcgaa cttcggagct cataggagaa ctcattattc tcgatttgct tcctcctgta 1020 tggaaggttg gccgcggagg cgtattccct cctgtgaatg agcagctcgt tgtgcaaatt 1080 gttaatgcaa acgtagaacg attgcattcc actttcgctc atgagccaca agcttatttg 1140 cgtatgatcg aaggtttggt aaccaatttc tttttcttac ctagcgagga agatccttct 1200 tcggttggga atatctaa 1218 121 726 DNA Homo sapiens 121 catatgcatc accatcacca tcacacaaag catggaaaac gcattcgtgg tatccaagag 60 acttacgatt tagctaagtc gtattctttg ggtgaagcga tagatatttt aaaacagtgt 120 cctactgtgc gtttcgatca aacggttgat gtgtctgtta aattagggat cgatccaaga 180 aagagtgatc agcaaattcg tggttcggtt tctttacctc acggtacagg taaagttttg 240 cgaattttag tttttgctgc tggagataag gctgcagagg ctattgaagc aggagcggac 300 tttgttggta gcgacgactt ggtagaaaaa atcaaaggtg gatgggttga cttcgatgtt 360 gcggttgcca ctcccgatat gatgagagag gtcggaaagc taggaaaagt tttaggtcca 420 agaaacctta tgcctacgcc taaagccgga actgtaacaa cagatgtggt taaaactatt 480 gcggaactgc gaaaaggtaa aattgaattt aaagctgatc gagctggtgt atgcaacgtc 540 ggagttgcga agctttcttt cgatagtgcg caaatcaaag aaaatgttga agcgttgtgt 600 gcagccttag ttaaagctaa gcccgcaact gctaaaggac aatatttagt taatttcact 660 atttcctcga ccatggggcc aggggttacc gtggatacta gggagttgat tgcgttataa 720 gaattc 726 122 330 PRT Homo sapiens 122 Met His His His His His His Met Ser Ile Arg Pro Thr Asn Gly Ser 5 10 15 Gly Asn Gly Tyr Pro Ser Ile Asn Pro Ser Asn Asp Asn Gln Tyr Gly 20 25 30 Leu Val Gln Ser Thr Ser Gly Pro Asn Tyr Gly Gly His Thr Val Ser 35 40 45 Ser Arg Gly Gly Phe Gln Gly Ile Cys Val Arg Ile Ala Asp Leu Phe 50 55 60 Arg Asn Cys Phe Ser Arg Asn Arg Gly Thr Thr Thr Thr Pro Ser Arg 65 70 75 80 Thr Val Ile Thr Gln Ala Asp Ile Tyr His Pro Thr Ile Ser Gly Gln 85 90 95 Gly Ala Gln Pro Ile Val Ser Thr Gly Asp Lys Lys Leu Asp Ser Ala 100 105 110 Ile Ile Gln Ala Asp Leu Arg Ala Gln Asn Lys Gln Thr Leu Ala Thr 115 120 125 His Ile Gln Ser Lys Leu Gly Ser Met Glu Gly Gln Ser Pro Gln Asp 130 135 140 Tyr Lys Ala Gly Ala Tyr Ser Ala Leu Arg Leu Met Leu Phe Thr Pro 145 150 155 160 Gly Glu Thr Thr Val Ser Ser Glu Arg Glu Arg Gln Ala Cys Val Thr 165 170 175 Gly Arg Asp Leu Trp Glu Gln Ala Ala Gly Asp Leu Ala Thr Asn Gly 180 185 190 Asn Thr Asp Gly Leu Met Leu Met Ala Asn Leu Ser Val Gly Gly Lys 195 200 205 His Val Pro Ala Gly His Leu Arg Glu Tyr Met Asp Thr Val Lys Gly 210 215 220 Thr Phe Thr Asp Glu Asn Glu Ala Thr Asp Pro Thr Val Asp Ala Ile 225 230 235 240 Leu Asp Leu Ala Ala Lys Ile Asp Ala Thr Glu Phe Ser Ser Pro Gly 245 250 255 Ser Gly Gln Val Ile Leu Asn Tyr Ile Gly Asn Tyr Gly Gln Val Val 260 265 270 Leu Glu Asn Glu Glu Met Asn Leu Leu Val Leu Glu Asp Gln Asn Gly 275 280 285 Gln Asp Pro Gln Arg Val Gln Asp Asn Ser Lys Glu Leu Gln Lys Leu 290 295 300 Leu Glu Asn Ala Arg Lys Thr Asp Pro Glu Leu Tyr Phe Gln Thr Leu 305 310 315 320 Thr Val Ile Thr Ser Ser Val Phe Leu Asp 325 330 123 405 PRT Homo sapiens 123 Met His His His His His His Val Ser Ser Ile Ser Pro Ile Gly Gly 5 10 15 Asn Ser Gly Pro Glu Gly Phe Ser Ser Ala Ser Arg Gly Asp Glu Ile 20 25 30 Asp Asp Val Pro Asp Ser Glu Glu Gly Glu Leu Glu Glu Arg Val Ser 35 40 45 Asp His Ala Glu Ser Ile Ile Thr Glu Ser Ser Glu Thr Leu Phe Arg 50 55 60 Thr Thr Ser Ser Ser Gly Val Ser Glu Asp Leu Gln Gln His Val Ser 65 70 75 80 Leu Glu Glu Ser Pro Arg Gln Arg Gly Phe Leu Gly Arg Ile Arg Asp 85 90 95 Ala Val Ala Ser Ile Trp Lys Arg Arg Val Ala Arg Arg Asn Glu Asn 100 105 110 Tyr Asp Val Lys Lys Ala Glu Glu Gln Gln Gly Ile Val Gln Tyr Leu 115 120 125 Gln Asp Ser Lys Met Pro Ala Leu Thr Arg Ala Tyr Arg His Leu Arg 130 135 140 Ala Phe Asn Ser Ala Cys Leu Arg Thr Ile Arg Glu Phe Phe Ala Thr 145 150 155 160 Ile Phe Arg Ala Leu Arg Asp Ala Tyr Tyr Arg His Cys Thr Arg Ser 165 170 175 Gly Ile Asn Phe Cys Gly Ala Asp Lys Asp Ser Leu Glu Val Leu Val 180 185 190 Ala Val Gly Leu Leu Leu Arg Met Ala Thr Leu Arg Ser Phe Glu His 195 200 205 Val Gly Gly Asn Tyr Glu Asp Arg Leu Val Asn Asn Asp Ala Pro Val 210 215 220 Thr Gly Ala Gly Arg Thr Leu Val Asp Asp Ala Val Asp Asp Ile Glu 225 230 235 240 Ser Ile Leu Asn Thr Arg Thr Asn Trp Pro Gln His Val Met Ile Gly 245 250 255 Phe Ser Arg Gly Leu Val Gln Leu Cys Ala Thr Pro Tyr Asn Ala Thr 260 265 270 Ser Gln Glu Cys Phe Lys Ser Ile Val Arg Leu Glu Lys Glu Asp Pro 275 280 285 Ser Ser Asp Tyr Ser Gln Ala Leu Leu Leu Ala Gly Ile Ile Asp Arg 290 295 300 Leu Ala Glu Lys Ala Pro Met Ala Ala Lys Tyr Val Leu Asp Ala Leu 305 310 315 320 Arg Val Arg Thr Ser Glu Leu Ile Gly Glu Leu Ile Ile Leu Asp Leu 325 330 335 Leu Pro Pro Val Trp Lys Val Gly Arg Gly Gly Val Phe Pro Pro Val 340 345 350 Asn Glu Gln Leu Val Val Gln Ile Val Asn Ala Asn Val Glu Arg Leu 355 360 365 His Ser Thr Phe Ala His Glu Pro Gln Ala Tyr Leu Arg Met Ile Glu 370 375 380 Gly Leu Val Thr Asn Phe Phe Phe Leu Pro Ser Glu Glu Asp Pro Ser 385 390 395 400 Ser Val Gly Asn Ile 405 124 238 PRT Homo sapiens 124 Met His His His His His His Thr Lys His Gly Lys Arg Ile Arg Gly 5 10 15 Ile Gln Glu Thr Tyr Asp Leu Ala Lys Ser Tyr Ser Leu Gly Glu Ala 20 25 30 Ile Asp Ile Leu Lys Gln Cys Pro Thr Val Arg Phe Asp Gln Thr Val 35 40 45 Asp Val Ser Val Lys Leu Gly Ile Asp Pro Arg Lys Ser Asp Gln Gln 50 55 60 Ile Arg Gly Ser Val Ser Leu Pro His Gly Thr Gly Lys Val Leu Arg 65 70 75 80 Ile Leu Val Phe Ala Ala Gly Asp Lys Ala Ala Glu Ala Ile Glu Ala 85 90 95 Gly Ala Asp Phe Val Gly Ser Asp Asp Leu Val Glu Lys Ile Lys Gly 100 105 110 Gly Trp Val Asp Phe Asp Val Ala Val Ala Thr Pro Asp Met Met Arg 115 120 125 Glu Val Gly Lys Leu Gly Lys Val Leu Gly Pro Arg Asn Leu Met Pro 130 135 140 Thr Pro Lys Ala Gly Thr Val Thr Thr Asp Val Val Lys Thr Ile Ala 145 150 155 160 Glu Leu Arg Lys Gly Lys Ile Glu Phe Lys Ala Asp Arg Ala Gly Val 165 170 175 Cys Asn Val Gly Val Ala Lys Leu Ser Phe Asp Ser Ala Gln Ile Lys 180 185 190 Glu Asn Val Glu Ala Leu Cys Ala Ala Leu Val Lys Ala Lys Pro Ala 195 200 205 Thr Ala Lys Gly Gln Tyr Leu Val Asn Phe Thr Ile Ser Ser Thr Met 210 215 220 Gly Pro Gly Val Thr Val Asp Thr Arg Glu Leu Ile Ala Leu 225 230 235 125 713 DNA Chlamydia trachomatis 125 ataacaatcc ctcccaatca tcgttgaacg tacaaggagg agccatctat gccaaaacct 60 ctttgtctat tggatcttcc gatgctggaa cctcctatat tttctcgggg aacagtgtct 120 ccactgggaa atctcaaaca acagggcaaa tagcgggagg agcgatctac tcccctactg 180 ttacattgaa ttgtcctgcg acattctcta acaatacagc ctctatagct acaccgaaga 240 cttcttctga agatggatcc tcaggaaatt ctattaaaga taccattgga ggagccattg 300 cagggacagc cattacccta tctggagtct ctcgattttc agggaatacg gctgatttag 360 gagctgcaat aggaactcta gctaatgcaa atacacccag tgcaactagc ggatctcaaa 420 atagcattac agaaaaaatt actttagaaa acggttcttt tatttttgaa agaaaccaag 480 ctaataaacg tggagcgatt tactctccta gcgtttccat taaagggaat aatattacct 540 tcaatcaaaa tacatccact catgatggaa gcgctatcta ctttacaaaa gatgctacga 600 ttgagtcttt aggatctgtt ctttttacag gaaataacgt tacagctaca caagctagtt 660 ctgcaacatc tggacaaaat acaaatactg ccaactatgg ggcagccatc ttt 713 126 780 DNA Chlamydia trachomatis 126 ccttctcctt actcaggagt tttaaaagaa aacgcaccgt ttttacgttt cctcacacaa 60 ttaactaaca agcatactca ttctggattt cattgcctcc taaaattctt agtcaaatcc 120 gaaagaagcc gacactcgag cgctcttctc ctaaaaatct tgttttttct ctgcttccga 180 gttataacgc ggctgtctca taacccacac taacatgatg aaacctctac gtttcggtta 240 tttcttttgc acaatctatt ttactttgtt acaggcagcg tttgctaaag aaccgaattc 300 ttgtcccgac tgccagaata attggaaaga agtcacccac acggatcaac tccctgaaaa 360 catcattcat gctgatgatg cttgttatca ctctggttat gtacaggctc tcattgatat 420 gcatttctta gatagctgct gccaggtcat cgttgaaaac caaactgctt acttattttc 480 tcttcctaca gatgatgtta cgcgcaacgc cattatcaac ctaattaaag accttccatt 540 cattcactcc gtagaaatct gccaagcatc ctatcaaacc tgtcatcatc aaggccctca 600 tggaaagact tctcttccag aacaacgttc tttctgtaca aaggtctgtg gaaaagaagc 660 tatttggtta ccacagaata ccatcctatt ctcgcctctt gtagcagata ctatccaagc 720 aactaatagt gcaggtatcc gttttaacga cgaagtcgta ggaaaacgtg ttggctctgc 780 127 433 DNA Chlamydia trachomatis 127 ctttaaagat tcgtcgtcct tttggtacta cgagagaagt tcgtgtgaaa tggcgttatg 60 ttcctgaagg tgtaggagat ttggctacca tagctccttc tatcagggct ccacagttac 120 agaaatcgat gagaagcttt ttccctaaga aagatgatgc gtttcatcgg tctagttcgc 180 tattctactc tccaatggtt ccgcattttt gggcagagct tcgcaatcat tatgcaacga 240 gtggtttgaa aagcgggtac aatattggga gtaccgatgg gtttctccct gtcattgggc 300 ctgttatatg ggagtcggag ggtcttttcc gcgcttatat ttcttcggtg actgatgggg 360 atggtaagag ccataaagta ggatttctaa gaattcctac atatagttgg caggacatgg 420 aagattttga tcc 433 128 803 DNA Chlamydia trachomatis 128 atctattaat taatagcaag cttgaaacta aaaacctaat ttatttaaag ctcaaaataa 60 aaaagagttt taaaatggga aattctggtt tttatttgta taacactgaa aactgcgtct 120 ttgctgataa tatcaaagtt gggcaaatga cagagccgct caaggaccag caaataatcc 180 ttgggacaac atcaacacct gtcgcagcca aaatgacagc ttctgatgga atatctttaa 240 cagtctccaa taattcatca accaatgctt ctattacaat tggtttggat gcggaaaaag 300 cttaccagct tattctagaa aagttgggag atcaaattct tgatggaatt gctgatacta 360 ttgttgatag tacagtccaa gatattttag acaaaatcaa aacagaccct tctctaggtt 420 tgttgaaagc ttttaacaac tttccaatca ctaataaaat tcaatgcaac gggttattca 480 ctcccagtaa cattgaaact ttattaggag gaactgaaat aggaaaattc acagtcacac 540 ccaaaagctc tgggagcatg ttcttagtct cagcagatat tattgcatca agaatggaag 600 gcggcgttgt tctagctttg gtacgagaag gtgattctaa gccctgcgcg attagttatg 660 gatactcatc aggcattcct aatttatgta gtctaagaac cagtattact aatacaggat 720 tgactccgac aacgtattca ttacgtgtag gcggtttaga aagcggtgtg gtatgggtta 780 atgccctttc taatctcgtg ccg 803 129 842 DNA Chlamydia trachomatis 129 tgggaatgtc gaagaatacg attacgttct cgtatctata ggacgccgtt tgaatacaga 60 aaatattggc ttggataaag ctggtgttat ttgtgatgaa cgcggagtca tccctaccga 120 tgccacaatg cgcacaaacg tacctaacat ttatgctatt ggagatatca caggaaaatg 180 gcaacttgcc catgtagctt ctcatcaagg aatcattgca gcacggaata tagctggcca 240 taaagaggaa atcgattact ctgccgtccc ttctgtgatc tttaccttcc ctgaagtcgc 300 ttcagtaggc ctctccccaa cagcagctca acaacaaaaa atccccgtca aagtaacaaa 360 attcccattt cgagctattg gaaaagcggt cgcaatgggc gaggccgatg gatttgcagc 420 cattatcagc catgagacta ctcagcagat cctaggagct tatgtgattg gccctcatgc 480 ctcatcactg atttccgaaa ttaccctagc agttcgtaat gaactgactc ttccttgtat 540 ttacgaaact atccacgcac atccaacctt agcagaagtt tgggctgaaa gtgcgttgtt 600 agctgctgat accccattac atatgccccc tgctaaaaaa tgaccgattc agaatctcct 660 actcctaaaa aatctatacc cgccagattc cctaagtggc tacgccagaa actcccttta 720 gggcgggtat ttgctcaaac tgataatact atcaaaaata aagggcttcc tacagtctgt 780 gaggaagcct cttgtccgaa tcgcacccat tgttggtcta gacatacagc tacctatcta 840 gc 842 130 813 DNA Chlamydia trachomatis 130 aaaatacttt gagctgcaca agctcccccc tgttctagag aagaacatga tgcaaattcc 60 aatccaccct taatcttttc aaagataaga tcttctgtag aatataaagc cgctccagac 120 aaagaagctt tcacgtcagt taatgtgatt ccagccttac tactatcccc aacaaaagca 180 atacctaaaa aagattctcc gtcacgagga gaatcaaggt tgctgctcgt aaaactacaa 240 attaaccctt gggaagagac ttgatcctgt tggtccacac cttggaaaac tacgggattg 300 gttactgaga acaaagtact ttgctctacc ttaccgggaa gagtatccgc atctttctct 360 tggaaagaac ttggatctcc tacaattaac ctatactgtc cttcagcctg actatcttta 420 gacccaacga atagatctcg aatttggtct aacaataaaa ccgcttgagg gcctacatat 480 accagctcat ttacagactg tcctccagca tgaagatcta cgcaactagc taacccgcta 540 acagaggcaa ggatagctgc tactacagac aaagaaaact tagaacaggt gctttttata 600 tctttctcgg aactcatttc aaacctgcga aatagcactt ttttgacaaa ctagcgtacc 660 gaaacaatcg gtccaacaac gcgttctgcc tatgatttca caaagacaaa acgacccata 720 gacaagctcc agagacgaca ttagagcttt agaccgtgga atgtacaatg ctgactgctt 780 tttgagaaag attttttata aagaacaggc cct 813 131 1947 DNA Chlamydia trachomatis 131 tcttttgcct atagagcaat ctcttatcat tgggtctgat ccaccagact atttcttcta 60 gatagagatt ctactacccc atccatggca ttcaacctct catcagtaaa cactttatta 120 gagttgttta tctgcccatc atcgatgata tcttctgaag tctttaatac cttcttacat 180 aagatccatc tctccggaga acagtgtcct tctatggata aaattcctac gcagatattc 240 acgcatccca aaatagcagg aatacctaga tagatggcat ttacaaacga agctgccgaa 300 actaggaata tcaaagcagt aatcactaaa agtagtccta tcaccactaa tcccacctta 360 aatgcagtgg aagatagaag attcgatata cgctctttca gtgttaatgg tgcagaacta 420 gtggaaatat cctgtgccga attggaagat ccagctcctt gaacaacggg tacagtgctc 480 atattttaca ttcctttttt ggttgtgagc agggagtcta cacaaacact tatttttttc 540 aaaaacccgt ctagaatatg ctctgagacc gaaaatgaac tcttttattt tcatatagat 600 aacaaaaaaa agccgcccag gaatccctgg acggcaccta cacatcgata aaatcaaaga 660 ttaatagatg tgtgtattct ctgtatcaga aactggaaca gtcaatgtat cggaagaaag 720 aatcgcttcc ccacgagcat ctccagctga tactgctttc aatgttacag aaaactctac 780 agtttcttta gaacctaatc taggtaacga atcgaatact actgtattgc ctgtaatcgt 840 tcctttagtt ggtccagaga aggatacagg ttgcagttct ttagagaatt taagcattaa 900 agaaacattt gtatcttctg cagaacctct gttggtgaca caaatacggt aaacagtatt 960 ttctcctaca caaacagggt cacaagtatc tactacgcac atatgagtag cagcaactcc 1020 tttccagtaa gttgtcgctt ctgcgcaaga agtacaagta ccacagtcag agcagctctt 1080 cacaacaaca ttatttgtga attgtccagg agtttgtgct cttactagaa ctttatactg 1140 tagagactct ccaggattca gttctttcac agtccaaact actttattac aagaaatttg 1200 agctcctgca gcttcaagaa ctgtgactcc gggagaaaga gtgtcttcaa cgacgacatc 1260 tcgcaacaca agatctccag gattggaaac ggagatcaca tattctacag gcttacaaac 1320 ataagaccaa tctgctcctg caatacttac ttgtacgcaa ggctcattga tcacagttgt 1380 tacgcttgct gtatttttat gtcctccaca gtaagaaacc gttgctatat tggtagcacg 1440 accacgttta agcggacaaa actctacagt aattgttctg tgctctccag gttgcatatc 1500 tccaagagta aacgtcagta cacgctgtcc agaagagtga gcgtaaccat ctggaacagg 1560 attttcaaca acaacgttac gagctattgc tgttccttgg ttcactacat taattttgta 1620 aactactggg caacgcaaac aagcattctc tgggccttct tgtttaacac agatagcagg 1680 ttgtccacat tttgtaaccg aacggatctc tggacaagcg catactgttg cagctgtaaa 1740 gcagcaacct tctttaagag gttttaccca tacagtaatt ttactctttt cgccttgtcc 1800 taagcggtca attttccaaa ctagcttacc atcagcagta ggagttgtcg ctggatcact 1860 gcgtacgaac tctgcttcac atggtaattg ctgagtaatg ataacatcaa cacaatccct 1920 tttacctgta gcagtaattt caatagg 1947 132 1278 DNA Chlamydia trachomatis 132 gataacaaaa aaaagccgcc caggaatccc tggacggcac ctacacatcg ataaaatcaa 60 agattaatag atgtgtgtat tctctgtatc agaaactgga acagtcaatg tatcggaaga 120 aagaatcgct tccccacgag catctccagc tgatactgct ttcaatgtta cagaaaactc 180 tacagtttct ttagaaccta atctaggtaa cgaatcgaat actactgtat tgcctgtaat 240 cgttccttta gttggtccag agaaggatac aggttgcagt tctttagaga atttaagcat 300 taaagaaaca tttgtatctt ctgcagaacc tctgttggtg acacaaatac ggtaaacagt 360 attttctcct acacaaacag ggtcacaagt atctactacg cacatatgag tagcagcaac 420 tcctttccag taagttgtcg cttctgcgca agaagtacaa gtaccacagt cagagcagct 480 cttcacaaca acattatttg tgaattgtcc aggagtttgt gctcttacta gaactttata 540 ctgtagagac tctccaggat tcagttcttt cacagtccaa actactttat tacaagaaat 600 ttgagctcct gcagcttcaa gaactgtgac tccgggagaa agagtgtctt caacgacgac 660 atctcgcaac acaagatctc caggattgga aacggagatc acatattcta caggcttaca 720 aacataagac caatctgctc ctgcaatact tacttgtacg caaggctcat tgatcacagt 780 tgttacgctt gctgtatttt tatgtcctcc acagtaagaa accgttgcta tattggtagc 840 acgaccacgt ttaagcggac aaaactctac agtaattgtt ctgtgctctc caggttgcat 900 atctccaaga gtaaacgtca gtacacgctg tccagaagag tgagcgtaac catctggaac 960 aggattttca acaacaacgt tacgagctat tgctgttcct tggttcacta cattaatttt 1020 gtaaactact gggcaacgca aacaagcatt ctctgggcct tcttgtttaa cacagatagc 1080 aggttgtcca cattttgtaa ccgaacggat ctctggacaa gcgcatactg ttgcagctgt 1140 aaagcagcaa ccttctttaa gaggttttac ccatacagta attttactct tttcgccttg 1200 tcctaagcgg tcaattttcc aaactagctt accatcagca gtaggagttg tcgctggatc 1260 actgcgtacg aactctgc 1278 133 916 DNA Chlamydia trachomatis 133 atggcgacaa tttaacgatt accggacaaa accatacatt atcatttaca gattctcaag 60 ggccagttct tcaaaattat gccttcattt cagcaggaga gacacttact ctgaaagatt 120 tttcgagttt gatgttctcg aaaaatgttt cttgcggaga aaagggaatg atctcaggga 180 aaaccgtgag tatttccgga gcaggcgaag tgattttttg ggataactct gtggggtatt 240 ctcctttgtc tattgtgcca gcatcgactc caactcctcc agcaccagca ccagctcctg 300 ctgcttcaag ctctttatct ccaacagtta gtgatgctcg gaaagggtct attttttctg 360 tagagactag tttggagatc tcaggcgtca aaaaaggggt catgttcgat aataatgccg 420 ggaattttgg aacagttttt cgaggtaata gtaataataa tgctggtagt gggggtagtg 480 ggtctgctac aacaccaagt tttacagtta aaaactgtaa agggaaagtt tctttcacag 540 ataacgtagc ctcctgtgga ggcggagtag tctacaaagg aactgtgctt ttcaaagaca 600 atgaaggagg catattcttc cgagggaaca cagcatacga tgatttaggg attcttgctg 660 ctactagtcg ggatcagaat acggagacag gaggcggtgg aggagttatt tgctctccag 720 atgattctgt aaagtttgaa ggcaataaag gttctattgt ttttgattac aactttgcaa 780 aaggcagagg cggaagcatc ctaacgaaag aattctctct tgtagcagat gattcggttg 840 tctttagtaa caatacagca gaaaaaggcg gtggagctat ttatgctcct acgtatcgat 900 ataagcacga atggag 916 134 751 DNA Chlamydia trachomatis misc_feature (1)...(751) n = A,T,C or G 134 agcctctggc gaaggagagc cataaaaagt gcctaccagc ggagaaacaa taaaatctcc 60 ctgagcaggc acctcacttt ctttcttctc gatactctct ttaacaatag gattcccaag 120 gttttgatct gaggataagt tttgaaatcc agcaaacagt ctgttatcat aaaagactgg 180 ctcctgaata cttgggactg tatccctttc taactctaac tccaaacctt cacgcttgat 240 aacaatgcgc ttcacgtgcc gaattcggca cgaggctctt tcttacgagg atctcgagtc 300 aagaagcctt gagccttcaa ttcttgcttc atgtcttctt tctcttgcag aacagctcta 360 gctaaaccca atcgagtagc aataacctga ccttgaaccc ctcctccact tactcggata 420 atcaaatcga aactgttgac atcaccgagc attctgagcg gagctaagat ggttgctctt 480 tgaacttcaa gagggaaata ttgctctaaa gtctttccat ttacgtcaat ttttccattc 540 ccagaacgaa gacgaacgca cacctgcttt cttctgcctg ttgcaacaga ctcttgtatc 600 atattctttg tcacaaatta ccccaaatta cgcgtctaaa acaattggtt tgatagcttc 660 atactgtgcg taagaactac ctttcaaaac tcttaaagat ttcatttgac gtcttccaag 720 ttttgtttta ggcaacattc nttaacagca t 751 135 410 DNA Chlamydia trachomatis 135 ataatccaga ctcttcctca tctggagata gcgctggaga ctctgaagaa ctgactgaga 60 cagaagctgg ttctacaaca gaaactccta ctttaatagg aggaggtgct atctatggag 120 aaactgttaa gattgagaac ttctctggcc aaggaatatt ttctggaaac aaagctatcg 180 ataacaccac agaaggctcc tcttccaaat ctgacgtcct cggaggtgcg gtctatgcta 240 aaacattgtt taatctcgat agcgggagct ctagacgaac tgtcaccttc tccgggaata 300 ctgtctcttc tcaatctaca acaggtcagg ttgctggagg agctatctac tctcctactg 360 taaccattgc tactcctgta gtattttcta aaaactctgc aacaaacaat 410 136 2719 DNA Chlamydia trachomatis 136 ctcgtgccga aaagctttct gctctaccaa agagattcgt tttttaaatt cttcattctc 60 tctaagagat ttagtttctt tcgcagaaca attgatagat actccgtacg tttggggtgg 120 ccggtgcatt cataaacagc ttcctcgtaa tggtgtagat tgttcggggt atattcaact 180 actttaccaa gtcacaggaa gaaatatccc tcgcaatgct agagatcaat acagagactg 240 ttctccagta aaagatttct cgtctctacc tataggagga cttatcttcc tcaagaaagc 300 aagcacggga caaatcaacc atgttatgat gaaaatctcg gagcatgaat tcattcatgc 360 tgcggaaaaa atagggaaag tagaaaaagt aatcctagga aatagggctt tctttaaagg 420 gaatctattc tgctcattag gtgaaccgcc tatagaagct gtttttggcg ttcctaaaaa 480 tagaaaagcc ttcttttgaa agaaggcttt tctgaaacgc actccaatat atggacaagc 540 aatagcttat cgtttggaga attggaaact cttacgagct ttcttacgac cgtatttttt 600 acgctctttc ttacgaggat ctcgagtcaa gaagccttga gccttcaatt cttgcttcat 660 gtcttctttc tcttgcagaa cagctctagc taaacccaat cgagtagcaa taacctgacc 720 ttgaacccct cctccactta ctcggataat caaatcgaaa ctgttgacat caccgagcat 780 tctgagcgga gctaagatgg ttgctctttg aacttcaaga gggaaatatt gctctaaagt 840 ctttccattt acgtcaattt ttccattccc agaacgaaga cgaacgctag aaacagcctg 900 ctttcttctg cctgttgcaa cagactcttg tatcatattc tttgtcacaa attaccccaa 960 attacgcgtc taaaacaatt ggtttgatag cttcatactg tgcgtaagaa ctacctttca 1020 aaactcttaa agatttcatt tgacgtcttc caagttttgt tttaggcaac attcctttaa 1080 cagcatgctc gataacataa gcaggctttc gcgcaatcat gttttcaaaa ggaacttctc 1140 gcatcccaga aataaagcct gtgtaatagt gatacacttt ctgagttcct tttgcgccag 1200 tcaaacgcac tttctcagca ttgatcacaa tgacaccatc tcccatcgct acgtgaggag 1260 taaaagtcac cttatgctta cctctcagga tcttcgcaac ttctgaagat aatctcccta 1320 aggtcttccc ttcagcatta actacatacc aggctttgtt tcgatcgtcc gaagccttag 1380 ctagggtcgt tttcgtatct tttctttttt ccataactta aatcacctta tcagagggaa 1440 tgattataat tttgatgatt attttttcca aacaaaaagc agctgtattt gccttctaaa 1500 gaatttagaa aagaaaaaat ttcaaaaaga tctcttttct ttttgccttc aaaaacagcc 1560 ttacacttct atacttcttt cgaaaaaata ttttagggaa gttcttgaat catgatttac 1620 ataataaaaa aaatagttag ctgccatcag ctaaatttaa aaaggtgcta ccagacgcta 1680 aaagctggtc cacgtaatta atatcataat cagaaagaag aaacttcgga ttatccaaca 1740 tgaactgatg aaaaggaatt gtagaatgca ccccaccaat atggaactct tttaaagctc 1800 ttttcataat ggctatcgct tcctctcgat tctttccttt tgtgattacc ttagcaatca 1860 tggaatcata ataaggaggt atcgcataac cactgtagca agccccgtct actcgcacag 1920 caggacctgc aggagggaga taataatcta atctaccagg ggaaggagta aagttattaa 1980 ttggatcctc tgcattgatt cggcattgaa tcacgtgccc tttaaactct atattctttt 2040 gcttccaagg cagtttttct cccttagcga cactaatctg agcctttaac aaatcgatcc 2100 ctgtcacttc ttccgtaata gtatgttcca cttggatacg cgtattcatc tccatgaaat 2160 aaaaacgctt ctccttatct aacagaaatt ctactgttcc aacagagaaa tacccggcac 2220 tccgagctaa atccactgct acttttccaa ctttagctcg catttctgga gttaaaatag 2280 gacttggagt ctcttctatt aatttttgcc gacgcctttg tactgacaat ctcgttctcc 2340 aagatacacg taatttccgt gcttatctcc aattacttga acttctaaat gtcttggatt 2400 ttcaataaat ttttcaatat acacgtcagg attattaaat cccgcttctg cttcagcccg 2460 agcggcagta aaagccctat agaattcgtc tttttctcta acaatccgta ttcctcgtcc 2520 accgcctcca gcaacagctt tgatgacgat ggggaatccg atcttttctg caattctaat 2580 cccttccacc tcatccttca ctacaccttc agatccaggg attacagggc acttaatctt 2640 tttagccaac tgcttagctg cgactttatc tcccatagtc gctatcgact cagcactagg 2700 accgataaat ctcgtgccg 2719 137 2354 DNA Chlamydia trachomatis 137 gtgcaagatg ggacgagttt gaagtttaat actagcacat aacttccctt ctggaggttt 60 aggagagagc ccttttatta gggctctctt tttttgtgtg tgaggaaagc tagcgtctaa 120 ctaaatgtct ctaagtaagg atgtttttag gggaaatagc gattttcagt gttgagaagc 180 ttagttacaa gacaataaac aaggctaaga aaaacctttc ttagccttgt ttctcaacga 240 atcgcctata gaagactaat cttccagcgt tgccctatgg ctcagcttca actggccttt 300 ttcgttaatg ctaaggagtt taacagcaag cttgtctcct tctttgacaa agccagagat 360 attgtctact ttttgtttag acaattcaga aatatgacag agcccttctt ttcctgggag 420 gacttctacg aatactccaa atgttgcgat agatgtaaca cggccattat aaactttacc 480 gacttcaact tctccagtta atccttcgat aagttcttta gctttgttaa tcgattcttg 540 ggtgcttgca gctatgttaa tgacgccgtc atcattgatg tcaacttgcg caccagaacg 600 ctcgataatt tgacggattt gttttcctcc gggaccaatg accgttgcga tttttgaggt 660 attgatctgc atagtttcaa tgcgcggagc atatttagaa acagttccct taggggaggc 720 cagaacctgt gtcataagat taaggatatg actacgccct tgtttagctt gcgctagagc 780 ttgctccata atcttatgag tgattccctc tatcttgata tccatttgga aagctgtaat 840 acctttagct gttccggcta ctttaaagtc catatctcct agatgatctt ctataccgga 900 aatatcagac aagatgatgg cttgatctcg atctaagatt aagcccatag caatacctgc 960 cacgggagct ttgataggaa ctccagcatc catgagtgca agacagcctc cacatacgga 1020 tgccatggag gaagatccat tagactcagt aatattagat tctaggcgaa tgatataagg 1080 gaatcgcgat gtctcaggaa gaacatgact taaagctttc tcagctaatt tcccatgtcc 1140 aatttcacgt cttcctgggg aaccaattct gccaacttct cctacggaga aaggagggaa 1200 gaaatactgt agatagaagc gagcggctcc atctccattc agatcttcga atcgctgtgc 1260 catattttcg cctccaagcg tacatacggc catgctttgc gtctctccgc gagtaaataa 1320 gcaacttccg tgtgttcttg gaagaaaagg agtctctatg gaaatggggc gaatctctgt 1380 ggtggttcgt ccatctacac gaataccaag atcttggata agagctcgca tttgattgga 1440 ttttgctgtc ttaaatgcag ccttaacgtt caacaaagaa aaatcactgt tttcttcttg 1500 aaccaagtta gcaataacgg attcctctaa ttctttcgag gcttgctcta gagcttcttt 1560 atctctaaaa gacaatgctt tttcgaattt ttctctaata aaatctgaaa ctacattttg 1620 tacgtcttct ggcatatcaa gaacggcaga gaaattcttt tgtttgccga tagctttctg 1680 ccatgcttca atagcatcgc atattttagc tatataggtt tgcccaaaaa caatagcttc 1740 tagaacttgc tcttctgtta aaaagtcgca atgtccttca atcattaaaa ctgcagaagc 1800 tgttcctgcc atgacgagat ccagcctgga ggcacttaac tcatctctgg ttgggttaat 1860 gacccacttt cctccgacga gcccaacgcg tacacccgca acgatacaat tttgaggaac 1920 ctctgagata gctaaagcgg cagaagctcc gcaaatagct agaggatcag gtaaagtttt 1980 cccgtcgtaa gaccaaacgt aggacaagac ttgaatatct tgcatgagtc tattaggaaa 2040 cgacggacgc aaagagcgat ccattagccg agaaacaaga atttctctct cggaaggccg 2100 tccttcacgt tttagaaatc ctccagaggt tcttcctgcg gaggaaaact tctcttgata 2160 gtctactctg aaaggcagaa aatcgacagc ctctgacaag gaggctgcac acgctgaaga 2220 aaaaacccaa gtctcgttca ttttgacgag aacagcccca ctggcctggc gagctatttt 2280 ccctgtctcg aaaattaatg ttttattttt gtctaacgca acagaaaaag tctcaaaagc 2340 atggagttg tcct 2354 138 898 DNA Chlamydia trachomatis 138 tcatcttgtc tgatatttcc ggtatagaag atcatctagg agatatggac tttaaagtag 60 ccggaacagc taaaggtatt acagctttcc aaatggatat caagatagag ggaatcactc 120 ataagattat ggagcaagct ctagcgcaag ctaaacaagg gcgtagtcat atccttaatc 180 ttatgacaca ggttctggcc tcccctaagg gaactgtttc taaatatgct ccgcgcattg 240 aaactatgca gatcaatacc tcaaaaatcg caacggtcat tggtcccgga ggaaaacaaa 300 tccgtcaaat tatcgagcgt tctggtgcgc aagttgacat caatgatgac ggcgtcatta 360 acatagctgc aagcacccaa gaatcgatta acaaagctaa agaacttatc gaaggattaa 420 ctggagaagt tgaagtcggt aaagtttata atggccgtgt tacatctatc gcaacatttg 480 gagtattcgt agaagtcctc ccaggaaaag aagggctctg tcatatttct gaattgtcta 540 aacaaaaagt agacaatatc tctggctttg tcaaagaagg agacaagctt gctgttaaac 600 tccttagcat taacgaaaaa ggccagttga agctgagcca tagggcaacg ctggaagatt 660 agtcttctat aggcgattcg ttgagaaaca aggctaagaa aggtttttct tagccttgtt 720 tattgtcttg taactaagct tctcaacact gaaaatcgct atttccccta aaaacatcct 780 tacttagaga catttagtta gacgctagct ttcctcacac acaaaaaaag agagccctaa 840 taaaagggct ctctcctaaa cctccagaag ggaagttatg tgctagtatt aaacttca 898 139 660 PRT Chlamydia trachomatis 139 Met His His His His His His Met Glu Ser Gly Pro Glu Ser Val Ser 5 10 15 Ser Asn Gln Ser Ser Met Asn Pro Ile Ile Asn Gly Gln Ile Ala Ser 20 25 30 Asn Ser Glu Thr Lys Glu Ser Thr Lys Ala Ser Glu Ala Ser Pro Ser 35 40 45 Ala Ser Ser Ser Val Ser Ser Trp Ser Phe Leu Ser Ser Ala Lys Asn 50 55 60 Ala Leu Ile Ser Leu Arg Asp Ala Ile Leu Asn Lys Asn Ser Ser Pro 65 70 75 80 Thr Asp Ser Leu Ser Gln Leu Glu Ala Ser Thr Ser Thr Ser Thr Val 85 90 95 Thr Arg Val Ala Ala Lys Asp Tyr Asp Glu Ala Lys Ser Asn Phe Asp 100 105 110 Thr Ala Lys Ser Gly Leu Glu Asn Ala Lys Thr Leu Ala Glu Tyr Glu 115 120 125 Thr Lys Met Ala Asp Leu Met Ala Ala Leu Gln Asp Met Glu Arg Leu 130 135 140 Ala Asn Ser Asp Pro Ser Asn Asn His Thr Glu Glu Val Asn Asn Ile 145 150 155 160 Lys Lys Ala Leu Glu Ala Gln Lys Asp Thr Ile Asp Lys Leu Asn Lys 165 170 175 Leu Val Thr Leu Gln Asn Gln Asn Lys Ser Leu Thr Glu Val Leu Lys 180 185 190 Thr Thr Asp Ser Ala Asp Gln Ile Pro Ala Ile Asn Ser Gln Leu Glu 195 200 205 Ile Asn Lys Asn Ser Ala Asp Gln Ile Ile Lys Asp Leu Glu Arg Gln 210 215 220 Asn Ile Ser Tyr Glu Ala Val Leu Thr Asn Ala Gly Glu Val Ile Lys 225 230 235 240 Ala Ser Ser Glu Ala Gly Ile Lys Leu Gly Gln Ala Leu Gln Ser Ile 245 250 255 Val Asp Ala Gly Asp Gln Ser Gln Ala Ala Val Leu Gln Ala Gln Gln 260 265 270 Asn Asn Ser Pro Asp Asn Ile Ala Ala Thr Lys Glu Leu Ile Asp Ala 275 280 285 Ala Glu Thr Lys Val Asn Glu Leu Lys Gln Glu His Thr Gly Leu Thr 290 295 300 Asp Ser Pro Leu Val Lys Lys Ala Glu Glu Gln Ile Ser Gln Ala Gln 305 310 315 320 Lys Asp Ile Gln Glu Ile Lys Pro Ser Gly Ser Asp Ile Pro Ile Val 325 330 335 Gly Pro Ser Gly Ser Ala Ala Ser Ala Gly Ser Ala Ala Gly Ala Leu 340 345 350 Lys Ser Ser Asn Asn Ser Gly Arg Ile Ser Leu Leu Leu Asp Asp Val 355 360 365 Asp Asn Glu Met Ala Ala Ile Ala Leu Gln Gly Phe Arg Ser Met Ile 370 375 380 Glu Gln Phe Asn Val Asn Asn Pro Ala Thr Ala Lys Glu Leu Gln Ala 385 390 395 400 Met Glu Ala Gln Leu Thr Ala Met Ser Asp Gln Leu Val Gly Ala Asp 405 410 415 Gly Glu Leu Pro Ala Glu Ile Gln Ala Ile Lys Asp Ala Leu Ala Gln 420 425 430 Ala Leu Lys Gln Pro Ser Ala Asp Gly Leu Ala Thr Ala Met Gly Gln 435 440 445 Val Ala Phe Ala Ala Ala Lys Val Gly Gly Gly Ser Ala Gly Thr Ala 450 455 460 Gly Thr Val Gln Met Asn Val Lys Gln Leu Tyr Lys Thr Ala Phe Ser 465 470 475 480 Ser Thr Ser Ser Ser Ser Tyr Ala Ala Ala Leu Ser Asp Gly Tyr Ser 485 490 495 Ala Tyr Lys Thr Leu Asn Ser Leu Tyr Ser Glu Ser Arg Ser Gly Val 500 505 510 Gln Ser Ala Ile Ser Gln Thr Ala Asn Pro Ala Leu Ser Arg Ser Val 515 520 525 Ser Arg Ser Gly Ile Glu Ser Gln Gly Arg Ser Ala Asp Ala Ser Gln 530 535 540 Arg Ala Ala Glu Thr Ile Val Arg Asp Ser Gln Thr Leu Gly Asp Val 545 550 555 560 Tyr Ser Arg Leu Gln Val Leu Asp Ser Leu Met Ser Thr Ile Val Ser 565 570 575 Asn Pro Gln Ala Asn Gln Glu Glu Ile Met Gln Lys Leu Thr Ala Ser 580 585 590 Ile Ser Lys Ala Pro Gln Phe Gly Tyr Pro Ala Val Gln Asn Ser Ala 595 600 605 Asp Ser Leu Gln Lys Phe Ala Ala Gln Leu Glu Arg Glu Phe Val Asp 610 615 620 Gly Glu Arg Ser Leu Ala Glu Ser Gln Glu Asn Ala Phe Arg Lys Gln 625 630 635 640 Pro Ala Phe Ile Gln Gln Val Leu Val Asn Ile Ala Ser Leu Phe Ser 645 650 655 Gly Tyr Leu Ser 660 140 598 PRT Chlamydia trachomatis 140 Met His His His His His His Met Ser Ile Arg Gly Val Gly Gly Asn 5 10 15 Gly Asn Ser Arg Ile Pro Ser His Asn Gly Asp Gly Ser Asn Arg Arg 20 25 30 Ser Gln Asn Thr Lys Gly Asn Asn Lys Val Glu Asp Arg Val Cys Ser 35 40 45 Leu Tyr Ser Ser Arg Ser Asn Glu Asn Arg Glu Ser Pro Tyr Ala Val 50 55 60 Val Asp Val Ser Ser Met Ile Glu Ser Thr Pro Thr Ser Gly Glu Thr 65 70 75 80 Thr Arg Ala Ser Arg Gly Val Leu Ser Arg Phe Gln Arg Gly Leu Val 85 90 95 Arg Ile Ala Asp Lys Val Arg Arg Ala Val Gln Cys Ala Trp Ser Ser 100 105 110 Val Ser Thr Ser Arg Ser Ser Ala Thr Arg Ala Ala Glu Ser Gly Ser 115 120 125 Ser Ser Arg Thr Ala Arg Gly Ala Ser Ser Gly Tyr Arg Glu Tyr Ser 130 135 140 Pro Ser Ala Ala Arg Gly Leu Arg Leu Met Phe Thr Asp Phe Trp Arg 145 150 155 160 Thr Arg Val Leu Arg Gln Thr Ser Pro Met Ala Gly Val Phe Gly Asn 165 170 175 Leu Asp Val Asn Glu Ala Arg Leu Met Ala Ala Tyr Thr Ser Glu Cys 180 185 190 Ala Asp His Leu Glu Ala Lys Glu Leu Ala Gly Pro Asp Gly Val Ala 195 200 205 Ala Ala Arg Glu Ile Ala Lys Arg Trp Glu Lys Arg Val Arg Asp Leu 210 215 220 Gln Asp Lys Gly Ala Ala Arg Lys Leu Leu Asn Asp Pro Leu Gly Arg 225 230 235 240 Arg Thr Pro Asn Tyr Gln Ser Lys Asn Pro Gly Glu Tyr Thr Val Gly 245 250 255 Asn Ser Met Phe Tyr Asp Gly Pro Gln Val Ala Asn Leu Gln Asn Val 260 265 270 Asp Thr Gly Phe Trp Leu Asp Met Ser Asn Leu Ser Asp Val Val Leu 275 280 285 Ser Arg Glu Ile Gln Thr Gly Leu Arg Ala Arg Ala Thr Leu Glu Glu 290 295 300 Ser Met Pro Met Leu Glu Asn Leu Glu Glu Arg Phe Arg Arg Leu Gln 305 310 315 320 Glu Thr Cys Asp Ala Ala Arg Thr Glu Ile Glu Glu Ser Gly Trp Thr 325 330 335 Arg Glu Ser Ala Ser Arg Met Glu Gly Asp Glu Ala Gln Gly Pro Ser 340 345 350 Arg Val Gln Gln Ala Phe Gln Ser Phe Val Asn Glu Cys Asn Ser Ile 355 360 365 Glu Phe Ser Phe Gly Ser Phe Gly Glu His Val Arg Val Leu Cys Ala 370 375 380 Arg Val Ser Arg Gly Leu Ala Ala Ala Gly Glu Ala Ile Arg Arg Cys 385 390 395 400 Phe Ser Cys Cys Lys Gly Ser Thr His Arg Tyr Ala Pro Arg Asp Asp 405 410 415 Leu Ser Pro Glu Gly Ala Ser Leu Ala Glu Thr Leu Ala Arg Phe Ala 420 425 430 Asp Asp Met Gly Ile Glu Arg Gly Ala Asp Gly Thr Tyr Asp Ile Pro 435 440 445 Leu Val Asp Asp Trp Arg Arg Gly Val Pro Ser Ile Glu Gly Glu Gly 450 455 460 Ser Asp Ser Ile Tyr Glu Ile Met Met Pro Ile Tyr Glu Val Met Asn 465 470 475 480 Met Asp Leu Glu Thr Arg Arg Ser Phe Ala Val Gln Gln Gly His Tyr 485 490 495 Gln Asp Pro Arg Ala Ser Asp Tyr Asp Leu Pro Arg Ala Ser Asp Tyr 500 505 510 Asp Leu Pro Arg Ser Pro Tyr Pro Thr Pro Pro Leu Pro Pro Arg Tyr 515 520 525 Gln Leu Gln Asn Met Asp Val Glu Ala Gly Phe Arg Glu Ala Val Tyr 530 535 540 Ala Ser Phe Val Ala Gly Met Tyr Asn Tyr Val Val Thr Gln Pro Gln 545 550 555 560 Glu Arg Ile Pro Asn Ser Gln Gln Val Glu Gly Ile Leu Arg Asp Met 565 570 575 Leu Thr Asn Gly Ser Gln Thr Phe Arg Asp Leu Met Lys Arg Trp Asn 580 585 590 Arg Glu Val Asp Arg Glu 595

Claims

What is claimed:

1. An isolated polynucleotide comprising a sequence selected from the group consisting of:

(a) sequences provided in SEQ ID NO: 1-48, 114-121, and 125-138;

(b) complements of the sequences provided in SEQ ID NO: 1-48, 114-121, and 125-138;

(c) sequences consisting of at least 20 contiguous residues of a sequence provided in SEQ ID NO: 1-48, 114-121, 125-138;

(d) sequences that hybridize to a sequence provided in SEQ ID NO: 1-48, 114-121, and 125-138, under highly stringent conditions;

(e) sequences having at least 95% identity to a sequence of SEQ ID NO: 1-48, 114-121, and 125-138;

(f) sequences having at least 99% identity to a sequence of SEQ ID NO: 1-48, 114-121, and 125-138; and

(g) degenerate variants of a sequence provided in SEQ ID NO: 1-48, 114-121, and 125-138.

2. An isolated polypeptide comprising an amino acid sequence selected from the group consisting of:

(a) sequences encoded by a polynucleotide of claim 1;

(b) sequences having at least 95% identity to a sequence encoded by a polynucleotide of claim 1; and

(c) sequences having at least 99% identity to a sequence encoded by a polynucleotide of claim 1.

3. An isolated polypeptide comprising at least an immunogenic fragment of a polypeptide sequence selected from the group consisting of:

(a) a polypeptide sequence set forth in SEQ ID NO: 122-124 and 139-140,

(b) a polypeptide sequence having at least 95% identity with a sequence set forth in SEQ ID NO: 122-124 and 139-140, and

(c) a polypeptide sequence having at least 99% identity with a sequence set forth in SEQ ID NO: 122-124 and 139-140.

4. An expression vector comprising a polynucleotide of claim 1 operably linked to an expression control sequence.

5. A host cell transformed or transfected with an expression vector according to claim 4.

6. An isolated antibody, or antigen-binding fragment thereof, that specifically binds to a polypeptide of claim 2 or claim 3.

7. A method for detecting the presence of Chlamydia in a patient, comprising the steps of:

(a) obtaining a biological sample from the patient;

(b) contacting the biological sample with a binding agent that binds to a polypeptide of claim 2 or claim 3;

(c) detecting in the sample an amount of polypeptide that binds to the binding agent; and

(d) comparing the amount of polypeptide to a predetermined cut-off value and therefrom determining the presence of Chlamydia in the patient.

8. A fusion protein comprising at least one polypeptide according to claim 2 or claim 3.

9. An oligonucleotide that hybridizes to a sequence recited in any one of SEQ ID NO: 1-48, 114-121, and 125-138 under highly stringent conditions.

10. A method for stimulating and/or expanding T cells specific for a Chlamydia protein, comprising contacting T cells with at least one component selected from the group consisting of:

(a) a polypeptide according to claim 2 or claim 3;

(b) a polynucleotide according to claim 1; and

(c) an antigen-presenting cell that expresses a polynucleotide according to claim 1,

under conditions and for a time sufficient to permit the stimulation and/or expansion of T cells.

11. An isolated T cell population, comprising T cells prepared according to the method of claim 10.

12. A composition comprising a first component selected from the group consisting of physiologically acceptable carriers and immunostimulants, and a second component selected from the group consisting of:

(a) a polypeptide according to claim 2 or claim 3;

(b) a polynucleotide according to claim 1;

(c) an antibody according to claim 6;

(d) a fusion protein according to claim 8;

(e) a T cell population according to claim 11; and

(f) an antigen presenting cell that expresses a polypeptide according to claim 2 or claim 3.

13. A method for stimulating an immune response in a patient, comprising administering to the patient a composition selected from the group consisting of:

(a) a composition of claim 12;

(b) a polynucleotide sequence of any one of SEQ ID NO: 80-94; and

(c) a polypeptide sequence of any one of SEQ ID NO: 95-109.

14. A method for the treatment of Chlamydia infection in a patient, comprising administering to the patient a composition selected from the group consisting of:

(a) a composition of claim 12;

(b) a polynucleotide sequence of any one of SEQ ID NO: 80-94; and

(d) a polypeptide sequence of any one of SEQ ID NO: 95-109.

15. A method for determining the presence of Chlamydia in a patient, comprising the steps of:

(a) obtaining a biological sample from the patient;

(b) contacting the biological sample with an oligonucleotide according to claim 9;

(c) detecting in the sample an amount of a polynucleotide that hybridizes to the oligonucleotide; and

(d) comparing the amount of polynucleotide that hybridizes to the oligonucleotide to a predetermined cut-off value, and therefore determining the presence of the cancer in the patient.

16. A diagnostic kit comprising at least one oligonucleotide according to claim 9.

17. A diagnostic kit comprising at least one antibody according to claim 6 and a detection reagent, wherein the detection reagent comprises a reporter group.

18. A method for the treatment of Chlamydia in a patient, comprising the steps of:

(a) incubating CD4+ and/or CD8+ T cells isolated from a patient with at least one component selected from the group consisting of:

(i) a polypeptide according to any one of claims 2 or 3;

(ii) a polypeptide sequence of any one of SEQ ID NO: 95-109;

(iii) a polynucleotide according to claim 1;

(iv) a polynucleotide sequence of any one of SEQ ID NO: 80-94;

(v) an antigen presenting cell that expresses a polypeptide sequence set forth in any one of claims 2 or 3;

(vi) an antigen presenting cell that expresses a polypeptide sequence of any one of SEQ ID NO: 95-109, such that the T cells proliferate; and

(b) administering to the patient an effective amount of the proliferated T cells.