AU2013205807A1

AU2013205807A1 - Protective proteins of S. agalactiae combinations thereof and methods of using the same

Info

Publication number: AU2013205807A1
Application number: AU2013205807A
Authority: AU
Inventors: Manfred Berger; Katherine Cohen; Barbara Maierhofer; Andreas Meinke; Eszter Nagy; Christina Neubauer; Beatrice Senn; Ulrike Stierschneider; Alexander Von Gabain
Original assignee: Intercell Austria AG
Current assignee: Valneva Austria GmbH
Priority date: 2007-01-12
Filing date: 2013-05-10
Publication date: 2013-05-30

Abstract

The invention relates to a composition comprising at least two protective proteins against Streptococcus agalactiae (S. agalactiae) or ftnctionally active variant thereof; a protective peptide against S. agalactiae; one or more nucleic acid(s) encoding the at least two proteins and/or the protective peptide; a method of producing the composition; a pharmaceutical composition, especially a vaccine, comprising the composition and/or at least one protective peptide; methods for producing antibodies; a mixture of antibodies against the at least two proteins of the composition; the use of the composition and/or at least one protective peptide and/or one or more nucleic acid(s) for the manufacture of a medicament for the immunization or treatment of a subject; methods of diagnosing a S. agalactiae infection; a method for identifying a ligand capable of binding the composition and/or at least one protective peptide; and the use of the composition and/or at least one protective peptide for the isolation and/or purification and/or identification of an interaction partner of the composition and/or peptide.

Description

Protective proteins of S. agalactiae, combinations thereof and methods of using the same 5 The invention relates to a composition comprising at least two protective proteins against Streptococcus agalactiae (S. agalactiae) or functionally active variants thereof; a protective peptide against S. agalactiae; one or more nucleic acid(s) encoding the at least two proteins and/or the protective peptide; a method of producing the composition; a 10 pharmaceutical composition, especially a vaccine, comprising the composition and/or at least one protective peptide; methods for producing antibodies; a mixture of antibodies against the at least two proteins of the composition; the use of the composition and/or at least one protective peptide and/or one or more nucleic acid(s) for the manufacture of a medicament for the immunization or treatment of a subject; methods of diagnosing a S, 15 agalacidae infection; a method for identifying a ligand capable of binding the composition and/or at least one protective peptide; and the use of the composition and/or at least one protective peptide for the isolation and/or purification and/or identification of an interaction partner of the composition and/or peptide. 20 S. agalactiae is an encapsulated gram-positive bacterium, which belongs to the Group B Streptococci (GBS) based on its haemolysis pattern on blood agar. Capsules form the basis for classifying GBS into nine distinct serotypes. Most of them have been shown to cause serious diseases, and the two most common scrotypes - type il and V - are estimated to account for the majority (~80%) of invasive diseases worldwide. The ranking and serotype 25 prevalence differs by age group and geographic area. Strepzococcus agalactiae is a frequent cause of infections in neonates, pregnant women and in chronically ill and elderly patients. In newborns Group B Streptococcus even represents the predominant pathogen in the United States causing life threatening diseases, 30 such as sepsis, pneumonia and meningitis. GBS diseases are associated with a high mortality rate (~5%) and a large percentage (--20%) of children surviving GBS infections becomes permanently handicapped with hearing, learning and visual disabilities.

-2 Newboms usually acquire the pathogen during delivery from their GBS-colonized mothers. Twenty-five to 40% of pregnant women are colonized with GBS, but are asymptomatic. Due to vertical transmission during birth, 50-70% of neonates born to colonized women - that is approximately 10-25% of all newborns - become colonized by 5 GBS during delivery which is a prerequisite for infection and disease. In the United States, GBS infections affect 1-5 newborns/1,000 live births. Pre-term infants are at the highest risk for invasive disease due to their immature immune system. and the low leve! of maternal antibody transfer before the 346 pregnancy week. 10 GBS disease occurs throughout the world. The highest prevalence of invasive disease in newborns occurs in Western countries, due to the elimination and reduction of other infectious agents and also due to the increased survival of very immature newborns. Before prevention by intrapartum antibiotic treatment was introduced, about 17,000 cases of invasive GBS diseases (sepsis, pneumonia and/or meningitis) were reported in the US 15 annually. The rates of serious GBS infections are higher among newborns than among any other age group. Nonetheless, serious Group B streptococcal infections occur in other age groups in both men and women. Among non-pregnant adults, rates of serious disease range from 4.1 to 7.2 cases per 100,000 and increase with age. The average death rate for invasive infections is 8-10% for adults between ages 18-64 and 15-25% for adults > 65 20 years of age. Serious disease is most common among elderly, bedridden patients and people suffering from severe medical conditions including diabetes mellitus, liver disease, history of stroke, history of cancer or bedsores. Currently, disease management fully relies on antibiotics, mainly Penicillin G. In order to 25 prevent invasive disease in newborns, pregnant women are screened for carriage of GBS at 35 t' to 37t weeks of gestation. Colonized mothers are then treated with high dose antibiotics during delivery to prevent neonatal GBS disease. Current standard treatment of GBS infections is also based on antibiotics. Route, dosage, 30 schedule and duration of therapy depend on the severity of the illness. Ten days of treatment is recommended for bacteraemia, pneumonia and soft tissue infections, while 2-3 weeks is recommended for meningitis and 3-4 weeks for osteomyelitis.

-3 Invasive GBS diseases are associated with 5% mortality and 20% permanent damage in spite of effective antibiotic therapy, due to a very rapid and dramatic clinical course. Before prevention direct medical costs of neonatal disease were -$300 million annually in the US; and GBS still poses a considerable economic burden. 5 Although intrapartum prophylaxis has decreased the incidence of early-onset GBS disease., currently available strategies are not ideal as they can neither prevent late-onset infections nor disease in premature babies which are at highest risk for invasive disease. 10 Currently, no effective preventive vaccine is available. There are efforts focusing on using capsular polysaccharides (with or without protein-conjugation) as immunogens, but several arguments militate against that approach. Polysaccharides induce IgG2 antibodies, which cross the placenta less efficiently than IgGI or IgG3 antibodies. This especially poses a problem for the most susceptible early-born neonates, since placental antibody transfer is 15 low before the 34 pregnancy week and about 10% of deliveries occur before that time. An additional disadvantage of polysaccharide vaccines is the incomplete vaccine coverage among GBS serotypes. Given adequate ecological pressure, replacement disease by non vaccine serotypes remains a real threat, particularly in areas with high disease burden. 20 Taking these insufficiencies into account, new generation immune interventions against GBS disease are needed. Given the very recent acceptance of the use of a cervical cancer preventing vaccine in teenage girls, a new approach would be the use of combinations of proteins as a prophylactic GBS vaccine in order to provide protection against more than one S. agalactiae strain or serotype. 25 Accordingly, one problem underlying the present invention was to provide alternative means for the development of medicaments such as vaccines against S agalactiae infection. More particularly, one problem was to provide combinations of protective proteins, particularly more effective combinations, derived from £ agalataiae that can be 30 used for the manufacture of said medicaments. Surprisingly, this object has been solved by combinations of protective proteins/peptides comprising or consisting of the amino acid sequences as defined in SEQ ID NOS: I to 6 or functionally active variants thereof.

4 Accordingly, the present invention relates to a composition comprising at least two proteins, which are: i) a protective protein comprising or consisting of the protective peptide with the 5 amino acid sequence of SEQ ID NO: 5 (gbsl478p) or functionally active variant thereof; and one or both of ii) a protective protein comprising or consisting of the protective peptide with the amino acid sequence of SEQ ID NO: 4 (gbs1477p) or functionally active variant 10 thereof; iii) a protective protein comprising or consisting of the protective peptide with the amino acid sequence of SEQ ID NO: 6 (gbs2018p) or functionally active variant thereof; optionally further comprising one or more proteins selected from the group consisting 15 of: iv) a protective protein comprising or consisting of the protective peptide with the amino acid sequence of SEQ ID NO: 1 (gbs0233p) or functionally active variant thereof; v) a protective protein comprising or consisting of the protective peptide with the 20 amino acid sequence of SEQ ID NO: 2 (gbs1087p) or functionally active variant thereof; vi) a protective protein comprising or consisting of the protective peptide with the amino acid sequence of SEQ ID NO: 3 (gbs1309p) or functionally active variant thereof. 25 Surprisingly, it was found that combinations of the above protective proteins provide a better protection against S. agalactiae than a protective protein when used alone. A better protection in the context of the present invention may refer to a situation in which protection provided by the combination is improved quantitatively in comparison to the 30 single components of the composition. For example, the combination may provide protection against at least one serotype of S. agalactiae against which at least one of the protective proteins present in the composition does not provide protection. Accordingly, the number of serotypes against which the combination provides protection is increased. Additionally or alternatively, protection provided by the combination is improved 35 qualitatively in comparison to the single components of the composition. For example, the survival of mice challenged with GBS strains may be improved when a composition of 4a protective proteins is used in comparison to the single components of the composition. Both, quantitatively and qualitatively sufficient protection, are important for successful prevention and/or treatment, since it is the goal striven for to provide protection which is as high as possible and which protects against as many serotypes as possible. 5 Additionally, combinations of different protective proteins are in general advantageous in comparison to single protective proteins, since in the case of vaccines employing different -5 protective proteins/antibodies the probability of a serotype switch of the pathogen in question leading to reduced effectiveness of the vaccine is strongly diminished. This is due to the fact that more than one mutation in S. agalactiae proteins at defined sites would be required in order to render the respective S. agalactiae strain unsusceptible to the vaccine. 5 The protective protein consisting of the amino acid sequence of SEQ ID NO: 1 is derived from S. agalactiae strain 12403 and has been denoted by gbs0233p (partial gbs0233) in accordance with the genome of NEM316 (ATCC12403). The DNA sequence encoding the full length protein gbs0233 (consisting of 308 amino acids; SEQ ID NO: 229) from which 10 the protective protein consisting of the amino acid sequence of the SEQ ID NO: I is derived is disclosed at GcnBank( accession number AL732656 (complete genome of Streptococcus agalactiae NEM316) and the amino acid sequence of the full length protein is disclosed in W02004/099242 (see SEQ ID NO: 475). The amino acid sequence of SEQ ID NO: I is disclosed in the Examples as well as in the attached Sequence listing. The 15 protective protein comprising or consisting of the protective peptide of SEQ ID NO: 1 or a functionally active variant thereof are referred to as (protective) proteins of subgroup i). The protective protein consisting of the amino acid sequence of SEQ ID NO: 2 is derived from S. agalactiae strain 6313 and has been denoted by gbsiO87p (partial gbsi087) in 20 accordance with the genome of NEM316 (ATCC12403). The amino acid and encoding DNA sequences of the fill length protein gbs 1087 (also referred to as FbsA and consisting of 442 amino acids; SEQ ID NO: 230) from which the protective protein consisting of the amino acid sequence of the SEQ ID NO: 2 is derived is disclosed in WO2004/03561 8 (see Fig. I and SEQ ID NO: 11). The amino acid sequence of SEQ ID NO: 2 is disclosed in the 25 Examples as well as in the attached Sequence listing. The protective protein comprising or consisting of the protective peptide of SEQ ID NO: 2 or a functionally active variant thereof are referred to as (protective) proteins of subgroup ii). The protective protein consisting of the amino acid sequence of SEQ ID NO: 3 is derived 30 from S. agalactiae strain 12403 and has been denoted by gbsI309p (partial gbs1309) in accordance with the genome of NEM316 (ATCC 12403). The DNA sequence encoding the full length protein gbsl309 (consisting of 403 amino acids; SEQ ID NO: 231) from which the protective protein consisting of the amino acid sequence of the SEQ ID NO: 3 is derived is disclosed in GenBank" accession number AL732656 (complete genome of -6 Streptococcus agalactiae NEM316) and the amino acid sequence of the fall length protein is disclosed in W02004/099242 (see SEQ ID NO: 307). The amino acid sequence of SEQ ID NO: 3 is disclosed in the Examples as well as in the attached Sequence listing. The protective protein comprising or consisting of the protective peptide of SEQ ID NO: 3 or a 5 functionally active variant thereof are referred to as (protective) proteins of subgroup iii). The protective protein consisting of the amino acid sequence of SEQ ID NO: 4 is derived from S. agalactiae strain 6313 and has been denoted by gbsl477p (partial gbs1477) in accordance with the genome of NEM316 (ATCC12403). The amino acid and encoding to DNA sequences of the full length protein gbs1477 (also referred to as PabB and consisting of 674 amino acids; SEQ ID NO: 232) from which the protective protein consisting of the amino acid sequence of the SEQ ID NO: 4 is derived is disclosed in WO2004/035618 (see Fig. 16 and SEQ ID NO: 18). The amino acid sequence of SEQ ID NO: 4 is disclosed in the Examples as well as in the attached Sequence listing. The protective protein comprising 15 or consisting of the protective peptide of SEQ ID NO: 4 or a functionally active variant thereof are referred to as (protective) proteins of subgroup iv). The protective protein consisting of the amino acid sequence of SEQ ID NO: 5 is derived from S. agalactiae strain 6313 and has been denoted by gbsl478p (partial gbs1478) in 20 accordance with the genome of NEM316 (ATCC12403). The amino acid and encoding DNA sequences of the full length protein gbs1478 (also referred to as PabA and consisting of 901 amino acids; SEQ ID NO: 233) from which the protective protein consisting of the amino acid sequence of the SEQ ID NO: 5 is derived is disclosed in W02004/035618 (see Fig. 16 and SEQ ID NO: 17). The amino acid sequence of SEQ ID NO: 5 is disclosed in 25 the Examples as well as in the attached Sequence listing. The protective protein comprising or consisting of the protective peptide of SEQ ID NO: 5 or a functionally active variant thereof are referred to as (protective) proteins of subgroup v). The protective protein consisting of the amino acid sequence of SEQ ID NO: 6 is derived 30 from S. agalactiae strain 12403 and has been denoted by gbs2018p (partial gbs2018) in accordance with the genome of NEM316 (ATCCl2403). The DNA sequence encoding the full length protein gbs2018 (also referred to as BibA (Santi et aL, 2007, Mol. Microbiol. 63:754-767) and consisting of 643 amino acids; SEQ ID NO: 234) from which the protective protein consisting of the amino acid sequence of the SEQ ID NO: 6 is derived is -7 disclosed at GenBank accession number AL732656 (complete genome of Streptococcus agalactiae NEM316) and the amino acid sequence of the fill length protein is disclosed in WO2004/099242 (see SEQ ID NO: 364). The amino acid sequence of SEQ ID NO: 6 is disclosed in the Examples as well as in the attached Sequence listing. The protective 5 protein comprising or consisting of the protective peptide of SEQ ID NO: 6 or a functionally active variant thereof arc referred to as (protective) proteins of subgroup vi). The combinations of the protective proteins of the sequences of SEQ ID NO: I to 6 have been shown to induce a protective immune response against different serotypes and/or to 10 show increased protection against S agalactiae in an animal model (see Examples). Functionally active variants may be obtained by changing the sequence of at least one of the protective proteins of SEQ ID NO: I to 6 and are characterized by having a biological activity similar to that displayed by the respective protective protein of the sequence of SEQ ID NO: I to 6 from which the variant is derived, including the ability to induce 15 protective immune responses and/or to show protection against S. agalactiae e.g. in an animal model, wherein any variant may be tested in any of the tests described in the Examples. The functionally active variant of a protective protein may be obtained by sequence alterations in the protective protein, wherein the protein with the sequence alterations essentially retains a function of the unaltered protective protein, e.g. having a 20 biological activity similar to that displayed by the unaltered protective protein (see above) including the ability to induce protective immune responses and/or to show protection against S. agalactiae. Such sequence alterations can include, but are not limited to, (conservative) substitutions, deletions, mutations and insertions. 25 In a preferred embodiment of the invention the composition comprises at least three proteins selected from the group consisting of subgroup i) to vi). In an even more preferred embodiment of the invention the composition comprises at least four proteins selected from the group consisting of subgroup i) to vi). 30 In a preferred embodiment of the invention the at least two, three or four proteins of the composition of the invention are selected from different subgroups i) to vi). Alternatively or additionally, at least two of the proteins of the composition of the invention are selected from one of the subgroups i) to vi).

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Examples of combinations of the first alternative (selection of protective proteins from different groups) are compositions comprising: - one protein of subgroup i) and one protein of subgroup ii); one protein ofsubgroup i) and one protein of subgroup iii); 5 - one protein of subgroup i) and one protein of subgroup iv); - one protein of subgroup i) and one protein of subgroup v); - one protein of subgroup i) and one protein of subgroup vi); - one protein of subgroup ii) and one protein of subgroup iii); - one protein of subgroup ii) and one protein of subgroup iv); 10 - one protein of subgroup ii) and one protein of subgroup v); - one protein of subgroup ii) and one protein of subgroup vi); - one protein of subgroup iii) and one protein of subgroup iv); - one protein of subgroup iii) and one protein of subgroup v); - one protein of subgroup iii) and one protein of subgroup vi); 15 - one protein of subgroup iv) and one protein of subgroup v); - one protein of subgroup iv) and one protein of subgroup vi); - one protein of subgroup v) and one protein of subgroup vi); - one protein of subgroup i) and one protein of subgroup ii) and one protein selected from any of the subgroups iii) to vi); 20 - one protein of subgroup i) and one protein of subgroup iii) and one protein selected from any of the subgroups ii) or iv) to vi); - one protein of subgroup i) and one protein of subgroup iv) and one protein selected from any of the subgroups ii), iii), v) or vi); - one protein of subgroup i) and one protein of subgroup v) and one protein selected 25 from any of the subgroups ii) to iv) or vi); - one protein of subgroup i) and one protein of subgroup vi) and one protein selected from any of the subgroups ii) to v); - one protein of subgroup ii) and one protein of subgroup iii) and one protein selected from any of the subgroups i) or iv) to vi); 30 - one protein of subgroup ii) and one protein of subgroup iv) and one protein selected from any of the subgroups i), iii), v) or vi); - one protein of subgroup ii) and one protein of subgroup v) and one protein selected from any of the subgroups i), iii), iv) or vi); -9 - one protein of subgroup ii) and one protein of subgroup vi) and one protein selected from any of the subgroups i) or iii) to v); - one protein of subgroup iii) and one protein of subgroup iv) and one protein selected from any of the subgroups i), ii), v) or vi); 5- one protein of subgroup iii) and one protein of subgroup v) and one protein selected from any of the subgroups i), ii), iv) or vi); - one protein of subgroup iii) and one protein of subgroup vi) and one protein selected from any of the subgroups i), ii), iv) or v); - one protein of subgroup iv) and one protein of subgroup v) and one protein selected 10 from any of the subgroups i) to iii) or vi); - one protein of subgroup iv) and one protein of subgroup vi) and one protein selected from any of the subgroups i) to iii) or v); or - one protein of subgroup v) and one protein of subgroup vi) and one protein selected from any of the subgroups i) to iv). 15 Preferred examples are: - one protein of subgroup iv) and one protein of subgroup vi); - one protein of subgroup iv), one protein of subgroup vi) and one protein of subgroup ii); 20 one protein of subgroup iv), one protein of subgroup vi), one protein of subgroup ii) and one protein of subgroup v); - one protein of subgroup iv), one protein of subgroup vi), one protein of subgroup ii) one protein of subgroup v) and one protein of subgroup i); one protein of subgroup iv), one protein of subgroup vi), one protein of subgroup ii), 25 one protein of subgroup v) and one protein of subgroup iii); or one protein of subgroup iv), one protein of subgroup vi), one protein of subgroup i), one protein of subgroup v), one protein of subgroup i) and one protein of subgroup iii). 30 In an alternative preferred embodiment of the invention at least two of the proteins of the composition of the invention may be selected from one of the subgroups i) to vi). The at least two proteins may be selected in order to cover different strains or serotypes of S. agalactiae and, accordingly, to provide protection against e.g. different strains or serotypes of S. agalactiae. The complete genorne of Streptococcus agalactiae NEM316 (strain -10 12403) is available at GenBank accession number AL732656. Furthermore, the complete or incomplete genomic sequences of the following strains of Streptococcus agalactiae are available at GenBank* (NIH genetic sequence database; http://wwwncbinhm.nihgov/) or NCBI (National Center for Biotechnology Information, Bethesda, MD, USA; 5 http://ww.ncbi.nlm.nih.gov/) using the indicated accession numbers: Strain Serotype Source 515 Ia NCBI: NZ AAJP00000000 GenBank: AAJP00000000 A909 ia'c NCBI: NC_007432 GenBank*: CPOOO114 H36B lb NCBI: NZAAJSOOOOOOO0 GenBank*: AAJSOOOOOOOO ISRS21 II NCBI NZAAJO00000000 GenBank": AAJOOOOOOOOO COH 1 -I- NCBI: NZAAJROOOOOOO0 GenBank*: AAJROOOOOOOO ATCC12403 III NCBT: NC 004368 (NEM316) GenBank*: AL732656 2603V/R V NCBI: NC_004116 GenBank-: AE009948 CJBI I V NCBI: NZ AAJQOOOO0000 GenBank> AAJQ00000000 Using the sequences of SEQ ID NO: I to 6 as specified in the present description and knowing the sequences of other S. agalactiae strains (e.g. vide supra) the skilled person is 10 able to identify the corresponding sequences of S. agalactiae strains other than 12403 (for SEQ ID NO: 1, 3 and 6) or 6313 (for SEQ ID NO: 2, 4 and 5) without undue burden. The corresponding sequences may be identified using e,g, the tools and sequences provided by "The Comprehensive Microbial Resource (CMR)" (see http://cmr.tigr.org/). However, it should be understood that the above strains are listed as examples of different S. agalactiae 15 strains and that the present invention is not to be limited to those strains.

- 11 Additionally, examples of sequences of the proteins corresponding to SEQ ID NO: I to 6 and derived from other serotypes are published or disclosed in: Protein or NCRI Accession Number (strain serotypee]) or SEQ ID NO Analogue gIs0233 Any sequence of SEQ ID NO: 55 to 60 (see Table 7), 229 and 235 to 286. gbsIO87 CAD12883 (6313); CAD27183 (706 S2 []a]); CAD27181 (SS1169 [V]); CAD27186 (090R); CAD27182 (0176 H4A [II]) or any sequence of SEQ ID NO: 67 to 72 (see Table 8), 230 and 287 to 316. gbsl309 Any sequence of SEQ ID NO: 79 to 84 (see Table 9), 231 and 317 to 359. gbs1477 Any sequence of SEQ ID NO: 91 to 132 (see Table 10), 223 to 228 (see Fig. 5), 232 and 360 to 362. gbs 1478 1 Any sequence of SEQ ID NO: 185 to 203 (see Table 11) 233 and 363 to 378. gbs2018 CAJ66802 (CCH57); CA366794 (CCH180); CAJ66788 (NEM1002); CA3 66790 (NEM 1560) or any sequence of SEQ ID NO: 175 to 179 (see Table 12), 234 and 379 to 425. 5 However, it should be understood that the present invention is not limited to the variants and corresponding proteins described above. Other naturally occurring proteins corresponding to those of SEQ ID NO: 1 to 6 may be identified as described above and used in order to carry out the present invention. 10 Examples of combinations of the second alternative (selection of protective proteins from one group only) are compositions comprising: - at least two different proteins of subgroup i), preferably selected from the group consisting of proteins comprising or consisting of SEQ ID NO: I or a naturally occurring variant thereof; - 12 at least two different proteins of subgroup ii), preferably selected from the group consisting of proteins comprising or consisting of SEQ ID NO: 2 or a naturally occurring variant thereof; at least two different proteins of subgroup iii), preferably selected from the group 5: consisting of proteins comprising or consisting of SEQ ID NO: 3 or a naturally occurring variant thereof; at least two different proteins of subgroup iv), preferably selected from the group consisting of proteins comprising or consisting of SEQ ID NO: 4 or a naturally occurring variant thereof; t1 at least two different proteins of subgroup v), preferably selected from the group consisting of proteins comprising or consisting of SEQ ID NO: 5 or a naturally occurring variant thereof; at least two different proteins of subgroup vi), preferably selected from the group consisting of proteins comprising or consisting of SEQ ID NO: 6 or a naturally occurring variant thereof; preferably at least two protective proteins each comprising or consisting of a sequence selected from SEQ ID NO: 55 to 60 (see Table 7), 235 to 286, and optionally 229; preferably at least two protective proteins each comprising or consisting of a sequence selected from SEQ ID NO: 67 to 72 (see Table 8), 287 to 316, and optionally 230; preferably at least two protective proteins each comprising or consisting of a sequence selected from SEQ ID NO: 79 to 84 (see Table 9), 317 to 359, and optionally 231; preferably at least two protective proteins each comprising or consisting of a sequence selected from SEQ ID NO: 185 to 203 (see Table 11), 363 to 378, and optionally 233; preferably at least two protective proteins each comprising or consisting of a sequence selected from SEQ ID NO: 175 to 179 (see Table 12), 379 to 425 and 34 optionally 234; or more preferably at least two protective proteins each comprising or consisting of a sequence selected from SEQ ID NO: 91 to 132 (see Table 10), 360 to 362, or 223 to 228 (see Fig. 5) and optionally 232.

- 13 In a preferred embodiment the naturally occurring variants are those derived from S. agalacriae strains selected from the group consisting of IC97, 1C98, 1C105, IC108, IC216, IC244, IC245, IC246, IC247, IC250, IC251, 1C252, 1C253, IC254, IC255, IC287, 1C288, 1C289, IC290, IC291, IC304, IC305, IC306, IC361, IC363, IC364, IC365, IC366, 10367, 5 IC368. IC377, IC379, IC432, IC434, IC455, IC457, 1C458, IC459, IC460, IC461, IC462, IC463, IC469, IC470, 126H4A, 5095S2, 6313, 12351, 12403 (NEM316), 12401, COHI, BAA23, 0176H4A, A909, C388/90, BAA22, 2603V/R, 49447, BAA611, 515, 1136B, 18RS2 1, CJB 111, and those disclosed in Tables 7 to 13. 10 In another preferred embodiment of the present invention the composition of the invention comprises - at least one protein of subgroup iv); - at least one protein of subgroup vi); at least one protein of subgroup iv) and at least one protein of subgroup vi); 15 - at least one protein of subgroup iv), at least one protein of subgroup vi) and at least one protein of subgroup ii); or - at least one protein of subgroup iv), at least one protein of subgroup vi), at least one protein of subgroup ii) and at least one protein of subgroup v). 20 In a preferred embodiment of the invention one of the at least two proteins comprises or consists of the protective peptide of SEQ ID NO: 4 (gbsI477p) or a functionally active variant thereof, preferably protective peptide of SEQ ID NO: 4 (gbsl477p) or a naturally occurring functionally active variant thereof, more preferably a naturally occurring functionally active variant as listed in Tables 10, 13, and in the Sequence listing. 25 In another preferred embodiment of the invention one of the at least two proteins comprises or consists of the protective peptide of SEQ ID NO: 6 (gbs2018p) or a functionally active variant thereof, preferably protective peptide of SEQ ID NO: 6 (gbs2018p) or a naturally occurring functionally active variant thereof, more preferably a 30 naturally occurring functionally active variant as listed in Tables 12, 13, and in the Sequence listing. In another preferred embodiment of the invention one of the at least two proteins comprises or consists of the protective peptide of SEQ ID NO: 2 (gbsl087p) or a -14 functionally active variant thereof, preferably protective peptide of SEQ ID NO: 2 (gbsl087p) or a naturally occurring functionally active variant thereof, more preferably a naturally occurring functionally active variant as listed in Tables 8, 13, and in the Sequence listing. S In another preferred embodiment of the invention one of the at least two proteins comprises or consists of the protective peptide of SEQ ID NO: 5 (gbsi478p) or a functionally active variant thereof, preferably protective peptide of SEQ ID NO: 5 (gbsl478p) or a naturally occurring functionally active variant thereof, more preferably a 10 naturally occurring functionally active variant as listed in Tables 11, 13, and in the Sequence listing. In another preferred embodiment of the invention one of the at least two proteins comprises or consists of the protective peptide of SEQ ID NO: I (gbs0233p) or a 15 functionally active variant thereof, preferably protective peptide of SEQ ID NO: 1 (gbs0233p) or a naturally occurring functionally active variant thereof, more preferably a naturally occurring functionally active variant as listed in Tables 7, 13, and in the Sequence listing. 20 In another preferred embodiment of the invention one of the at least two proteins comprises or consists of the protective peptide of SEQ ID NO: 3 (gbs1309p) or a functionally active variant thereof, preferably protective peptide of SEQ ID NO: 3 (gbsl309p) or a naturally occurring functionally active variant thereof, more preferably a naturally occurring functionally active variant as listed in Tables 9, 13, and in the Sequence 25 listing, In a more referred embodiment of the invention the at least two proteins of the composition of the invention encompass: - the protective peptide of SEQ ID NO: 4 (gbs 147'p) and the protective peptide of SEQ 30 ID NO: 6 (ghs2018p); - the protective peptide of SEQ ID NO: 4 (gbsI477p) and the protective peptide of SEQ ID NO: 6 (gbs2018p) and the protective peptide of SEQ ID NO: 2 (gbs1O87p); or - 15 - the protective peptide of SEQ ID NO: 4 (gbsl477p) and the protective peptide of SEQ ID NO: 6 (gbs20i8p) and the protective peptide of SEQ ID NO: 2 (gbs1087p) and the protective peptide of SEQ ID NO: 5 (gbsi478p). 5 In a further preferred embodiment of the invention a naturally occurring functionally active variant of any of the protective peptides of SEQ ID NO: I to 6 of the above list of compositions may be used, Examples of the resulting combinations are: I. the protective peptide of SEQ ID NO: 4 (gbs1477p) and a naturally occurring 10 functionally active variant of SEQ ID NO: 6 (gbs2018p); IL a naturally occurring functionally active variant of SEQ ID NO: 4 (gbsI477p) and the protective peptide of SEQ ID NO: 6 (gbs20l8p); IIL, a naturally occurring functionally active variant of SEQ ID NO: 4 (gbsl477p) and a naturally occurring functionally active variant of SEQ ID NO: 6 (gbs20l 8p); 15 IV. the protective peptide of SEQ ID NO: 4 (gbsi477p) and the protective peptide of SEQ ID NO: 6 (gbs2018p) and a naturally occurring functionally active variant of SEQ I D NO: 2 (gbsI087p); V. the protective peptide of SEQ ID NO: 4 (gbs1477p) and a naturally occurring functionally active variant of SEQ ID NO: 6 (gbs2018p) and the protective peptide of 20 SEQ ID NO: 2 (gbsl087p); VL a naturally occurring functionally active variant of SEQ ID NO: 4 (gbs1477p) and the protective peptide of SEQ ID NO: 6 (gbs2018p) and the protective peptide of SEQ ID NO: 2 (gbs087p); VII. a naturally occurring functionally active variant of SEQ ID NO: 4 (gbs1477p) and a 25 naturally occurring functionally active variant of SEQ ID NO: 6 (gbs2018p) and the protective peptide of SEQ ID NO: 2 (gbs087p); VII the protective peptide of SEQ ID NO: 4 (gbsi477p) and a naturally occurring functionally active variant of SEQ ID NO: 6 (gbs2018p) and a naturally occurring functionally active variant of SEQ ID NO: 2 (gbsi087p); 30 IX, a naturally occurring functionally active variant of SEQ ID NO: 4 (gbsl477p) and the protective peptide of SEQ ID NO: 6 (gbs2018p) and a naturally occurring functionally active variant of SEQ ID NO: 2 (gbsi 08 7 p); -16 X. a naturally occurring functionally active variant of SEQ ID NO: 4 (gbs1477p) and a naturally occurring functionally active variant of SEQ ID NO: 6 (gbs20l8p) and a naturally occurring functionally active variant of SEQ ID NO: 2 (gbsI087p); XL. any of the compositions of I to X in combination with the protective peptide of SEQ 5 ID NO: 5 (gbsl478p); or XII. any of the compositions of I to X in combination with a naturally occurring functionally active variant of SEQ ID NO: 5 (gbsi478p). wherein the naturally occurring functionally active variant is selected form those listed in to Tables 7 to 13 and Fig. 5 and those of SEQ ID NO: 229 to 234 and 235 to 425. Preferred S, agalactiae strains from which the naturally occurring functionally active variant may be derived include IC97, IC98, IC105, IC108, IC216, IC244, IC245, IC246, IC247, IC250, IC251, IC252, IC253, IC254, IC255, IC287, 1C288, IC289, IC290, IC291, 15 IC304, IC305, IC306, 10361, IC363, IC364, IC365, IC366, 10367, 10368, 1C377, 1C379, 1C432, 1C434, IC455, 1C457, IC458, 1C459, 1C460, 1C461. 1C462, IC463, IC469, IC470, 126H4A, 5095S2, 6313, 12351, 12403 (NEM316), 12401, COHl, BAA23, 0176H4A, A909, C388/90, BAA22, 2603V/R, 49447, BAA6l. 515, H36B, 18RS21, CJBii, and those disclosed in Tables 7 to 13. 20 In one embodiment of the invention two or more proteins of the at least two proteins of the composition of the invention may be combined into at least one fusion protein. The resulting fusion protein may encompass two or more of the proteins of subgroups i), ii), iii), iv), v) and/or vi) as defined above. Any of the specific combinations mentioned above 25 may be combined into at least one fusion protein. The fusion protein may encompass e.g, the same protein components as described in the section "examples of combinations of the first alternative (selection of protective proteins from different groups)" for the components of the composition, wherein the proteins can be arranged in the fusion protein in any suitable manner. 30 The fusion protein may comprise or consist of two or more proteins as defined above. Additionally, the fusion protein may encompass a linker, such as a protein linker, to connect the two or more proteins or additional C- or N-terminal sequences, such as a tag in order to purify the fusion protein. Additional sequences may also result from genetic - 17 engineering and the use of suitable restriction sites when preparing the nucleic acid sequences underlying the fusion protein. The proteins of subgroup i), ii), iii), iv), v) and/or vi) combined in a fusion protein may be 5 directly joined to each other or may be combined over a linker. The linker may be e.g. a short amino acid sequence. The linker may result from the genetic engineering of a suitable fusion protein or may be introduced in order to allow the single proteins to operate effectively. 10 In a preferred embodiment the functionally active variant a) is a functionally active fragment of the protective peptide, the functionally active fragment comprising at least 50% of the sequence of the protective peptide, preferably at least 70%, more preferably at least 80%, still more preferably at least 90%, even more preferably at least 95% and most preferably at least 97%, 98% or 15 99%; b) is derived from the protective peptide by at least one amino acid substitution, addition and/or deletion, wherein the functionally active variant has a sequence identity to the protective peptide or to the functionally active fragment as defined in a) of at least 40%, preferably at least 60%, more preferably at least 75%, still more 20 preferably at least 90%, even more preferably at least 95% and most preferably at least 97%, 98% or 99%; and/or c) consists of the protective peptide or a functionally active variant thereof and additionally at least one amino acid heterologous to the protective peptide, preferably wherein the functionally active variant is derived from or identical to any of the 25 naturally occurring variants of any of the sequences of SEQ ID NO: 55 to 60, 67 to 72, 79 to 84, 91 to 132, 175 to 179, 185 to 203, 223 to 234, and 235 to 425. The combinations of protective peptides of SEQ ID NO: I to 6 have been shown to induce a protective immune response against different serotypes and/or to show protection against 30 S, agalactiae in a sepsis model (see Examples). Functionally active variants may be obtained by changing the sequence of the protective peptide as defined above and are characterized by having a biological activity similar to that displayed by the respective protective peptide of the sequence of SEQ ID NO: I to 6 from which the variant is derived, including the ability to induce protective immune responses and/or to show protection - 18 against S. agalactiae e.g. in a sepsis model, wherein any variant may be tested in any of the tests described in the Examples within a composition of at least two proteins as defined above. The functionally active variant of a protective peptide may be obtained by sequence alterations in the protective peptide, wherein the peptide with the sequence alterations 5 retains a function of the unaltered protective peptide, e.g. having a biological activity similar to that displayed by the unaltered protective peptide (see above), when used in combination of the invention. Such sequence alterations can include, but are not limited to, (conservative) substitutions, additions, deletions, mutations and insertions. 10 The variant of the protective peptide is ftnctionally active in the context of the present invention, if the activity of the composition of the invention including the variant (but not the original protein) amounts to at least 10%, preferably at least 25%, more preferably at least 50%, even more preferably at least 70%, still more preferably at least 80%, especially at least 90%, particularly at least 95 %, most preferably at least 99% of the activity of the 15 composition of the invention including the protective peptide without sequence alteration (i.e. the original protein). The activity of the composition including the variant may be determined or measured as described in the Examples and then compared to that obtained for the composition including the respective protective peptide of the amino acid sequence of SEQ ID NO: I to 6 instead of the variant. 20 The functionally active fragment of the protective peptide is characterized by being derived from the protective peptide of SEQ ID NO: I to 6 by one or more deletions resulting in a peptide comprising at least 50% of the sequence of the protective peptide, preferably at least 70%, more preferably at least 80%, still more preferably at least 90%, even more 25 preferably at least 95% and most preferably at least 97%, 98% or 99%. Sequence identity may be determined as described below. The deletion(s) may be C-terminally, N-terminally and/or internally. Preferably the fragment is obtained by 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, more preferably 1, 2, 3, 4 or 5, even more preferably 1, 2 or 3, still more preferably I or 2, most preferably I deletion(s). 30 Alternatively or additionally, the variant may be obtained from the protective peptide by at least one amino acid substitution, addition and/or deletion, wherein the functionally active variant has a sequence identity to the protective peptide or to the functionally active fragment as defined in a) of at least 40%, preferably at least 60%, more preferably at least - 19 75%, still more preferably at least 90%, even more preferably at least 95% and most preferably at least 97%, 98% or 99%. Sequence identity may be determined as described below. The substitution(s), addition(s) and/or deletion(s) may be C-terminally, N terminally and/or internally. Preferably, the functionally active variant is obtained from the 5 protective peptide or the fragment, preferably the protective peptide, by 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, more preferably 1, 2, 3, 4 or 5, even more preferably 1, 2 or 3, still more preferably 1 or 2, most preferably I amino acid substitution(s), addition(s) and/or deletion(s). 10 Furthermore, the variant may consist of the protective peptide or the functionally active variant thereof, preferably the variant of a) and/or b), and at least one amino acid residue heterologous to the protective peptide or variant thereof, such as a marker protein. The feature "heterologous amino acid" or "amino acid heterologous to the protective peptide or variant thereof' refers to any amino acid which is different from that amino acid located 15 adjacent to the protective protein in any naturally occurring protein of S. agalactiae, particularly from that of strain 12403 (for SEQ ID NO: 1, 3 and 6) or 6313 (for SEQ ID NO: 2, 4 and 5), especially the sequence made reference to above. The one or more additional amino acids may be C-terminally, N-terminally or C- and N-terminally to the protective peptide or variant thereof. 20 The substituted or additional sequence or amino acid residue(s) as defined above consists of (an) amino acid residue(s), which may be any amino acid, which may be either an L and/or a D-amino acid, naturally occurring and otherwise. Preferably the amino acid is any naturally occurring amino acid such as alanine, cysteine, aspartic acid, glutamic acid, 25 phenylalanine, glycine, histidine, isoleucine, lysine, leucine, methionine, asparagine, proline, glutamine, arginine, serine, threonine, valine, tryptophan or tyrosine. However, the amino acid may also be a modified or an unusual amino acid, Examples of those are 2-aminoadipic acid, 3-aminoadipic acid, beta-alanine, 2-arninobutyric acid, 4 30 aminobutyric acid, 6-aminocaproic acid, 2-aminoheptanoic acid, 2-aminoisobutyric acid, 3-aminoisobutyric acid, 2-aminopimelic acid, 2,4-diaminobutyric acid, desmosine, 2,2' diaminopimelic acid, 2,3-diaminopropionic acid, N-ethylglycine, N-ethylasparagine, hydroxylysine., allo-hydroxylysine, 3-hydroxyproline, 4-hydroxyproline, isodesmosine, allo-isoleucine, N-methylglycine, N-methylisoleucine, 6-N-methyllysine, N-methylvaline, -20 norvaline, norleucine or ornithine. Additionally, the amino acid may be subject to modifications such as posttranslational modifications. Examples of modifications include acetylation, amidation, blocking, formylation, gamma-carboxyglutamic acid hydroxylation, glycosylation, methylation, phosphorylation and sulfatation. If more than 5 one substituted or additional heterologous amino acid residue is present in the peptide, the amino acid residues may be the same or different from one another. In one preferred embodiment of the invention, the functionally active variant of the peptide of the invention is essentially identical to the protective peptide of subgroups i) to vi), but in differs from the peptide of the SEQ ID NO: I to 6, respectively, in that it is derived from a homologous sequence of a different strain or even serotype of S. agalactiae. As detailed above different strains and scrotypes of S. agalactiae have been identified so far. Accordingly, any of these serotypes may be the basis for the functionally active variant. These are referred to as naturally occurring variants (see also above). Preferably, these 15 naturally occurring variants are derived from S. agalactiace strains selected from the group consisting of IC97, IC98, IC105, IC108, IC216, IC244, IC245, IC246, IC247, IC250, 1C251, IC252, IC253, IC254, IC255, IC287, PC288, 1C289, IC290, IC291, IC304, IC305, 1C306, IC361, IC363, IC364, IC365, IC366, IC367, IC368, IC377, IC379, 1C432, 1C434, IC455, IC457, IC458, IC459. IC460, 1C461. IC462, IC463, IC469, IC470, 1261-4A, 20 5095S2, 6313, 12351, 12403 (NEM316), 12401, COHI, BAA23, 0176H4A, A909, C388/90, BAA22, 2603V/R, 49447, BAA611, 515, H36B, 18RS21, CJ111, and those disclosed in Tables 7 to 13. However, the term "functionally active variant" includes naturally occurring allelic 25 variants, as well as mutants or any other non-naturally occurring variants. As is known in the art, an allelic variant is an alternate form of a (poly)peptide that is characterized as having a substitution, deletion, or addition of one or more amino acids that does essentially not alter the biological function of the polypeptide. By "biological function" is meant a function of the peptide in the cell it naturally occurs in, even if the function is not 30 necessary for the growth or survival of the cells. For example, the biological function of a porin is to allow the entry into cells of compounds present in the extracellular medium. The biological function is distinct from the antigenic function. A polypeptide can have more than one biological function.

- 21 Accordingly, the present invention also relates to compositions comprising protective peptides including functionally active variants thereof of different S. agalactiae isolates. Such homologues may easily be identified and isolated based on the nucleic acid and amino acid sequences disclosed herein as discussed above. A homologous protective 5 peptide of a different strain or even serotype may be identified by e.g. sequence alignment. The homologous sequence may vary from any of the protective peplides of subgroups i) to vi), by one or more amino acid substitutions, deletions and/or additions. Percentage of sequence identity can be determined e.g. by sequence alignment. Methods of 11 alignment of sequences for comparison are well known in the art. Various programs and alignment algorithms have been described e.g. in Smith and Waterman, Adv. App. Math. 2: 482, 1981 or Pearson and Lipman, Proc. Natt Acad. Sci. U.S.A. 85: 2444-2448, 1988. The NCBI Basic Local Alignment Search Tool (NCBI BLAST) (Altschul et al., . Mo. 15 Biol. 215: 403-410, 1990) is available from several sources, including the National Center for Biotechnology Information (NCBI, Bethesda, MD) and on the Intemet, for use in connection with the sequence analysis programs blastp, blast, blastx, tblastn and tblastx. Variants, e.g. of any protective peptide of the sequences of SEQ ID NO: I to 6, are typically characterized using the NCBI Blast 2.0, gapped blastp set to default parameters. 20 For comparisons of amino acid sequences of e.g. at least 85 amino acids, the "Blast 2 sequences" function may be employed using the default BLOSUM62 matrix set to default parameters, (gap existence cost of 11, and a per residue gap cost of 1). In a preferred embodiment, the functionally active variant derived from the peptide as 25 defined above by amino acid exchanges, deletions or insertions may also conserve, or more preferably improve, the activity (as defined above). Furthermore, these peptides may also cover epitopes, which trigger the same or preferably an improved T cell response. These epitopes are referred to as "heteroclitic". They have a similar or preferably greater affinity to MHC/HLA molecules, and the ability to stimulate the T cell receptors (TCR) directed to 30 the original epitope in a similar or preferably stronger manner. Heteroclitic epitopes can be obtained by rational design i. e. taking into account the contribution of individual residues to binding to MHC/HLA as for instance described by (Rammensee, H. et al., 1999, Immunogenetics. 50: 213-219), combined with a systematic exchange of residues potentially interacting with the TCR and testing the resulting sequences with T cells - 22 directed against the original epitope. Such a design is possible for a skilled man in the art without much experimentation. Conservative substitutions are those that take place within a family of amino acids that are 5 related in their side chains and chemical properties. Examples of such families are amino acids with basic side chains, with acidic side chains, with non-polar aliphatic side chains, with non-polar aromatic side chains, with uncharged polar side chains, with small side chains, with large side chains etc.. In one embodiment, one conservative substitution is included in the peptide. In another embodiment, two conservative substitutions or less are 10 included in the peptide. In a further embodiment, three conservative substitutions or less are included in the peptide. Examples of conservative amino acid substitutions include, but are not limited to, those listed below: 15 Original Residue Conservative Substitutions Ala Ser Arg Lys Ast Gln; His 20 Asp Glu Cys Ser Gin Asn GIu Asp His Asn; Gin 25 lie Leu; Val Leu Ile; Val Lys Arg; Gin; Asn Met Leu; Ile Phe Met; Leu; Tyr 30 Ser Thr Thr Ser Trp T[yr Tyr Trp; Phe Val Ile; Leu - 23 In another embodiment of the invention the peptide as defined above may be modified by a variety of chemical techniques to produce derivatives having essentially the same activity (as defined above for fragments and variants) as the modified peptides, and optionally 5 having other desirable properties. For example, carboxylic acid groups of the protein, whether C-terminal or side chain, may be provided in the form of a salt of a pharmaceutically-acceptable cation or esterified to form an ester, or converted to an amide, Amino groups of the peptide, whether amino-terminal or side chain, may be in the form of a pharmaceutically-acceptable acid addition salt, such as the HC, HBr, acetic, benzoic, to toluene sulfonic, naleic, tartaric and other organic salts, or may be converted to an aide. Hydroxyl groups of the peptide side chains may be converted to alkoxy or to an ester using well recognized techniques. Phenyl and phenolic rings of the peptide side chains may be substituted with one or more halogen atoms, such as fluorine, chlorine, bromine or iodine, or with alkyl, alkoxy, carboxylic acids and esters thereof, or amides of such carboxylic 15 acids. Thiols can be protected with any one of a number of well recognized protecting groups, such as acetamide groups. Peptides of this invention may be in combination with outer surface proteins or other proteins or antigens of other proteins. In such combination, the peptide may be in the form 20 of a fusion protein. The peptides/proteins of the composition of the invention may be optionally fused to a selected peptide or protein derived from other microorganisms. For example, a peptide or protein may be fused at its N-terminus or C-terminus to a polypeptide from another pathogen or to more than one polypeptide in sequence. Peptides which may be useful for this purpose include polypeptides identified by the prior art. 25 In a preferred embodiment of the invention a protein/peptide of the composition of the invention is fused to an epitope tag which provides an epitope to which an anti-tag substance can selectively bind. The epitope tag is generally placed at the N- or C-terminus of the peptide but may be incorporated as an internal insertion or substitution as the 30 biological activity permits. The presence of such epitope-tagged forms of a peptide can be detected using a substance such as an antibody against the tagged peptide. Also, provision of the epitope tag enables the peptide to be readily purified by affinity purification using an anti-tag antibody or another type of affinity matrix that binds to the epitope tag. Various tag polypeptides and their respective antibodies are well known in the art. Examples -24 include a poly-histidine (poly-his) tag, e.g. a hexa-histidine tag as described in the Examples, a poly-histidine-glycine (poly-his-gly) tag, the HA tag polypeptide, the c-myc tag, the Strcp tag and the FLAG tag. 5 Fusions also may include the peptides/proteins of the composition of this invention fused or coupled to moietics other than amino acids, including lipids and carbohydrates. Further, peptides/proteins/compositions of this invention may be employed in combination with other vaccinal agents described by the prior art, as well as with other types of vaccinal agents derived from other microorganisms. Such peptides/proteins are useful in the 10 prevention, treatment and diagnosis of diseases caused by a wide spectrum of Streptococcus isolates. These fusion proteins are constructed for use in the methods and compositions of this invention. These fusion proteins or multimeric proteins may be produced recombinantly, or 15 may be synthesized chemically. The peptides and proteins described herein may be prepared by any of a number of conventional techniques. Desired peptides may be chemically synthesized. An alternative approach involves generating the fragments of known peptides by enzymatic digestion, 20 e.g., by treating the protein with an enzyme known to cleave proteins at sites defined by particular amino acid residues, or by digesting the DNA with suitable restriction enzymes, expressing the digested DNA and isolating the desired fragment. Yet another suitable technique involves isolating and amplifying a DNA fragment encoding a desired peptide fragment, by polymerase chain reaction (PCR). Oligonucleotides that define the desired 25 termini of the DNA fragment are employed as the 5' and 3' primers in the PCR. Techniques for making mutations, such as deletions, insertions and substitutions, at predetermined sites in DNA, and therefore in proteins having a known sequence are well known. One of skill in the art using conventional techniques, such as PCR, may readily use the peptides, proteins and compositions provided herein to identify and isolate other similar proteins. 30 Such methods are routine and not considered to require undue experimentation, given the information provided herein. For example, variations can be made using oligonucleotide mediated site-directed mutagenesis (Carter et al., Nucl. Acids Res., 13:4431 (1985); Zoller et al., Nucl. Acids Res. 10:6487 (1987)), cassette mutagenesis (Wells et al., Gene, 34:315 (1985)), restriction selection mutagenesis (Wells et al., Philos. Trans. R. Soc. London - 25 SerA, 317:415 (1986)), PCR mutagenesis, or other known techniques can be performed on the cloned DNA to produce the peptide or composition of the invention. Another subject of the invention relates to a protective peptide consisting of the amino acid 5 sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 55 to 57, 59, 60, 68, 69, 71, 72, 79 to 84, 91 to 132, 175 to 179, 185 to 203, 223 to 234, and 235 to 425 which have been shown to provide protection against S. agalactiae (see Examples). 10 Another subject of the invention relates to one or more nucleic acid(s) encoding the at least two proteins comprised in the composition according to the invention and/or any of the protective peptides according to the invention. Nucleic acid molecules of the present invention may be in the form of RNA, such as 15 nRNA or cRNA, or in the form of DNA, including, for instance, cDNA and genomic DNA e.g. obtained by cloning or produced by chemical synthetic techniques or by a combination thereof The DNA may be triple-stranded, double-stranded or single-stranded. Single-stranded DNA may be the coding strand, also known as the sense strand, or it may be the non-coding strand, also referred to as the anti-sense strand. Nucleic acid molecule as 20 used herein also refers to, among others, single- and double-stranded DNA, DNA that is a mixture of single- and double-stranded RNA, and RNA that is a mixture of single- and double-stranded regions, hybrid molecules comprising DNA and RNA that may be single stranded or, more typically, double-stranded, or triple-stranded, or a mixture of single- and double-stranded regions. In addition, nucleic acid molecule as used herein refers to triple 25 stranded regions comprising RNA or DNA or both RNA. and DNA. The nucleic acid may be a fragment of a nucleic acid occurring naturally in S. agalactiae. The nucleic acid also includes sequences that are a result of the degeneration of the genetic code. There are 20 natural amino acids, most of which are specified by more than one 30 codon. Therefore, all nucleotide sequences are included in the invention which result in the peptide as defined above. Preferred examples of the nucleic acid(s) encoding the at least two proteins comprised in the composition according to the invention and/or any of the protective peptides according - 26 to the invention are those comprising or consisting of at least one nucleic acid sequence selected from the group consisting of SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 61 to 66, SEQ ID NO: 73 to 78, SEQ ID NO: 85 to 90, SEQ ID NO: 133 to 174, SEQ ID NO: 180 to 184 and SEQ ID 5 NO: 204 to 222. The above sequences are indicated in the Examples, Tables 7 to 12 and the attached Sequence listing. Additionally, the nucleic acid may contain one or more modified bases. Such nucleic acids may also contain modifications e.g. in the ribose-phosphate backbone to increase stability to and half life of such molecules in physiological environments. Thus, DNAs or RNAs with backbones modified for stability or for other reasons are "nucleic acid molecules" as that feature is intended herein. Moreover, DNAs or RNAs comprising unusual bases, such as inosine, or modified bases, such as tritylated bases, to name just two examples, are nucleic acid molecules within the context of the present invention. It will be appreciated that a 15 great variety of modifications have been made to DNA and RNA that serve many useful purposes known to those of skill in the art. The term nucleic acid molecule as it is employed herein embraces such chemically, enzymatically or metabolically modified forms of nucleic acid molecule, as well as the chemical forms of DNA and RNA characteristic of viruses and cells, including simple and complex cells, inter alia, For 20 example, nucleotide substitutions can be made which do not affect the peptide or protein or composition of the invention encoded by the nucleic acid, and thus any nucleic acid molecule which encodes an antigenic peptide or functionally active variant thereof or a composition of the invention as defined above is encompassed by the present invention. 25 Furthermore, any of the nucleic acid molecules encoding a peptide or composition of the invention can be functionally linked, using standard techniques such as standard cloning techniques, to any desired regulatory sequences, whether a S. agalactiae regulatory sequence or a heterologous regulatory sequence, heterologous leader sequence, hetero logous marker sequence or a heterologous coding sequence to create a fusion protein. 30 The nucleic acid of the invention may be originally formed in vitro or in a cell in culture, in general, by the manipulation of nucleic acids by endonucleases and/or exonucleases and/or polymerases and/or ligases and/or recombinases or other methods known to the skilled practitioner to produce the nucleic acids.

- 27 In one embodiment of the invention, the nucleic acid(s) according to the invention is/are located in a vector or a cell other than S. agalacriae. 5 A vector may further include nucleic acid sequences that permit it to replicate in the host cell, such as an origin of replication, one or more therapeutic genes and/or selectable marker genes and other genetic elements known in the art such as regulatory elements directing transcription, translation and/or secretion of the encoded peptide or protein. The vector may be used to transduce, transform or infect a cell, thereby causing the cell to 10 express nucleic acids and/or proteins other than those native to the cell. The vector optionally includes materials to aid in achieving entry of the nucleic acid into the cell, such as a viral particle, liposome, protein coating or the like. Numerous types of appropriate expression vectors for protein expression are known in the art, which may be used in standard molecular biology techniques. Such vectors are selected from among 15 conventional vector types including insects, e.g., baculovirus expression, or yeast, fungal, bacterial or viral expression systems. Other appropriate expression vectors, of which numerous types are known in the art, can also be used for this purpose. Methods for obtaining such expression vectors are well-known (see, e.g. Sambrook et as., Molecular Cloning. A Laboratory Manual, 2nd edition, Cold Spring Harbor Laboratory, New York 20 (1989)). In one embodiment, the vector is a viral vector. Viral vectors include, but are not limited to, retroviral and adenoviral vectors. Suitable host cells or cell lines for transfection by this method include bacterial cells. For example, the various strains of E. coli are well-known as host cells in the field of 25 biotechnology. Various strains of B. subtilis, Pseudomonas, Streptomyces, and other bacilli and the like may also be employed in this method. Many strains of yeast cells known to those skilled in the art are also available as host cells for expression of the peptides of the present invention. Other fungal cells or insect cells such as Spodopteraftugipedera (Sf9) cells may also be employed as expression systems. Alternatively, mammalian cells, such as 30 human 293 cells, Chinese hamster ovary cells (CHO), the monkey COS-1 cell line or murine 3T3 cells derived from Swiss, BALB/c or NIH mice may be used. Still other suitable host cells, as well as methods for transfection, culture, amplification, screening, production, and purification are known in the art.

-28 A further subject of the invention relates to a method of producing the composition according to the invention or the protective peptide according to the invention, comprising (a) introducing the one or more nucleic acids into a host cell; (b) expressing the protein(s) and/or peptide(s) encoded by the nucleic acid by culturing 5 the host cell under conditions conducive to the expression of the protein(s) and/or peptide(s); and (c) collecting and/or isolating the expressed protein(s) and/or peptide(s) of step (b). A peptide or composition of the invention or component thereof may be produced by 10 expressing a nucleic acid of the invention in a suitable host cel. The nucleic acid encoding the peptide/protein can be introduced into a host cell by any conventional technique. The host cells can e.g. be tansfected, e.g. by conventional means such as electroporation with at least one expression vector containing a nucleic acid of the invention under the control of a transcriptional regulatory sequence. The transfected or transformed host cell is then 15 cultured under conditions that allow expression of the protein. The expressed protein is recovered, isolated, and optionally purified from the cell (or from the culture medium, if expressed extracellularly) by appropriate means known to one of skill in the art. For example, the proteins are isolated in soluble form following cell lysis, or extracted using known techniques, e.g. in guanidine chloride. If desired, the peptides or fragments of the 20 invention are produced as a fusion protein. Such fusion proteins are those described above. Alternatively, for example, it may be desirable to produce fusion proteins to enhance expression of the protein in a selected host cell or to improve purification. The molecules comprising the peptides and compositions of this invention may be further purified using any of a variety of conventional methods including, but not limited to: liquid 25 chromatography such as normal or reversed phase, using HPLC, FPLC and the like; affinity chromatography (such as with inorganic ligands or monoclonal antibodies); size exclusion chromatography; immobilized metal chelate chromatography; gel electrophoresis; and the like. One of skill in the art may select the most appropriate isolation and purification techniques without departing from the scope of this invention. 30 Such purification provides the peptide/protein/composition in a form substantially free from other proteinaceous and non-proteinaceous materials of the microorganism. Still another subject of the invention relates to a pharmaceutical composition, especially a vaccine, comprising - 29 (i) the composition according to the invention and/or at least one protective peptide according to the invention; and (ii) optionally a pharmaceutically acceptable carrier or excipient. 5 A peptide or composition of the invention may be used for methods for immunizing or treating humans andlor animals with the disease caused by infection with S. agalactiae. Therefore, the peptide or composition may be used within a pharmaceutical composition. The pharmaceutical composition of the present invention may further encompass pharmaceutically acceptable carriers and/or excipients. The pharmaceutically acceptable 1a carriers and/or excipients useful in this invention are conventional and may include buffers, stabilizers, diluents, preservatives, and solubilizers. Remington's Pharmaceutical Sciences, by E. W. Martin, Mack Publishing Co,, Easton, PA, 15th Edition (1975), describes compositions and formulations suitable for pharmaceutical delivery of the (poly)peptides/proteins herein disclosed. 15 If the pharmaceutical composition comprises at least two protective proteins as defined above, the proteins of subgroup i) to vi) may be formulated into one or more pharmaceutical composition(s). Additionally, the two or more pharmaceutical composi tions may be administered together, simultaneously or consecutively. 20 In general, the nature of the carrier or excipients will depend on the particular mode of administration being employed. For instance, parenteral formulations usually comprise injectable fluids that include pharmaceutically and physiologically acceptable fluids such as water, physiological saline, balanced salt solutions, aqueous dextrose, glycerol or the 25 like as a vehicle. For solid compositions (e. g. powder, pill, tablet, or capsule forms), conventional non-toxic solid carriers can include, for example, pharmaceutical grades of mannitol, lactose, starch, or magnesium stearate. In addition to biologically neutral carriers, pharmaceutical compositions to be administered can contain minor amounts of non-toxic auxiliary substances, such as wetting or emulsifying agents, preservatives, and 30 pH1 buffering agents and the like, for example sodium acetate or sorbitan monolaurate. In a preferred embodiment the pharmaceutical composition further comprises an immunostimulatory substance such as an adjuvant. The adjuvant can be selected based on the method of administration and may include mineral oil-based adjuvants such as Freund's -30 complete and incomplete adjuvant, Montanide incomplete Seppic adjuvant such as ISA or ISA206 (SEPPIC, Paris, France), oil in water emulsion adjuvants such as the Ribi adjuvant system, syntax adjuvant formulation containing muramyl dipeptide, 10 J5 (Intercell; a synthetic adjuvant comprising the peptide motif KLK [WO 02/32451] and an 5 oligonucleotide [WO 01/93905]), or aluminum salt adjuvants, preferably aluminum hydroxide or aluminum phosphate. In a more preferred embodiment the immunostimulatory substance is selected from the group comprising polycationic polymers, especially polycationic peptides such as 10 polyarginine, immunostimulatory deoxynucleotides (ODNs), especially O1igo(dldC)n, peptides containing at least two LysLeuLys motifs, especially KLKLLLLLKLK, neuroactive compounds, especially human growth hormone, alum, adjuvants and combinations thereof, Preferably the combination is either a polycationic polymer and immunostimulatory deoxynucleotides or of a peptide containing at least two LysLeuLys 15 motifs and immunostimulatory deoxynucleotides. In a still more preferred embodiment the polycationic polymer is a polycationic peptide. The term "Oligo(dIdC)j" as used in the present invention means a phosphodiester backboned single-stranded DNA molecule containing 13 deoxy (inosine-cytosine) motifs, 20 also defined by the term [oligo-d(iChf]. The exact sequence is 5' didCdldCdldCdldCdldCdldCdldCdldCdldCdIdCdldCdIdCdIdC-3'. Oligo(dIdC) 13 can also be defined by the terms (oligo-dlC2j); oligo-dC 2 &m.; oligo-deoxy IC, 26-mer; or oligo-dlC, 26-mer, as specified for example in WO 01/93903 and WO 01/93905. 25 In an even more preferred embodiment of the invention the immunostimulatory substance is at least one immunostimulatory nucleic acid. Immunostimulatory nucleic acids are e.g. natural or artificial CpG containing nucleic acids, short stretches of nucleic acids derived from non-vertebrates or in form of short oligonucleotides (ODNs) containing non methylated cytosine-guanine dinucleotides (CpG) in a defined base context (e.g. as 3o described in WO 96/02555). Alternatively, also nucleic acids based on inosine and cytidine as e.g. described in WO 01/93903, or deoxynucleic acids containing deoxy-inosine and/or deoxyuridine residues (described in WO 01/93905 and WO 02/095027) may preferably be used as imrnmunostimulatory nucleic acids in the present invention. Preferably, mixtures of different immunostimulatory nucleic acids are used in the present invention. Additionally, -31 the aforementioned polycationic compounds may be combined with any of the immunostimulatory nucleic acids as aforementioned. Preferably, such combinations are according to the ones described in WO 01/93905, WO 02/32451, WO 01/54720, WO 01/93903, WO 02/13857, WO 02/095027 and WO 03/047602. In addition or alternatively, such a vaccine composition may comprise a neuroactive compound. Preferably, the neuroactive compound is human growth factor, e.g. described in WO 01/24822. Also preferably, the neuroactive compound is combined with any of the polycationic compounds and/or immunostimulatory nucleic acids as defined above. I0 In a highly preferred embodiment of the invention, the adjuvants are those used in the Examples, e.g. Complete Freund's adjuvant, aluminum hydroxide or/and an adjuvant comprising the KLKLLLLLKLK peptide and [dIdC]i 3 phosphodiester ssDNA, such as IC31* (Intercell AG, Vienna, Austria; described above). '5 The composition may be used e.g. for immunization or treatment of a subject. The pharmaceutical composition encompasses at least one peptide or composition of the invention; however, it may also contain a cocktail (i.e., a simple mixture) containing different peptides and/or compositions of the invention, optionally mixed with different 20 antigenic peptides or proteins of other pathogens. Such mixtures of these peptides, polypeptides, proteins or fragments or variants thereof are useful e.g. in the generation of desired antibodies to a wide spectrum of S agalactiae isolates. The (poly)peptide(s)/com position(s) of the present invention may also be used in the form of a pharmaceutically acceptable salt. Suitable acids and bases which are capable of forming salts with the 25 peptides of the present invention are well known to those of skill in the art, and include inorganic and organic acids and bases. Still another subject of the invention relates to a pharmaceutical composition comprising (i) the one or more nucleic acid(s) according to the invention or one or more nucleic 30 acid(s) complementary thereto, and (ii) optionally a pharmaceutically acceptable carrier or excipient. The nucleic acid sequences, alone or in combination with other nucleic acid sequences encoding peptides/proteins/compositions or antibodies or directed to other pathogenic - 32 microorganisms, may further be used as components of a pharmaceutical composition. The composition may be used for immunizing or treating humans and/or animals with the disease caused by infection with S. agalactiae. 5 The pharmaceutically acceptable carrier or excipient may be as defined above. In another embodiment, the nucleic acid sequences of this invention, alone or in combination with nucleic acid sequences encoding other antigens or antibodies from other pathogenic microorganisms, may further be used in compositions directed to actively 10 induce a protective immune response in a subject to the pathogen. These components of the present invention are useful in methods for inducing a protective immune response in humans arid/or animals against infection with & agalactiae. For use in the preparation of the therapeutic or vaccine compositions, nucleic acid delivery 15 compositions and methods are useful, which are known to those of skill in the art. The nucleic acids of the present invention or one or more nucleic acid(s) complementary thereto may be employed in the methods of this invention or in the compositions described herein as DNA sequences, either administered as naked DNA, or associated with a pharmaceutically acceptable carrier and provide for in viva expression of the antigen, 20 peptide or polypeptide. So-called "naked DNA" may be used to express the peptide or composition of the invention in vivo in a patient. (See, e.g., J. Cohen, Science, 259:1691 1692, which describes similar uses of "naked DNA"). For example, "naked DNA" associated with regulatory sequences may be administered therapeutically or as part of the vaccine composition e.g., by injection. 25 Alternatively, a nucleic acid encoding a peptide or composition of the invention or a nucleic acid complementary thereto may be used within a pharmaceutical composition, e.g. in order to express the peptide or composition of the invention in vivo, e.g., to induce antibodies. 30 A preferred embodiment of the invention relates to a pharmaceutical composition, wherein the nucleic acid is comprised in a vector and/or a cell other than S. agalactiae. Vectors and cells suitable in the context of the present invention are described above. Vectors are particularly employed for a DNA vaccine. An appropriate vector for delivery may be -33 readily selected by one of skill in the art. Exemplary vectors for in vivo gene delivery are readily available from a variety of academic and commercial sources, and include, e.g., adeno-associated virus (International patent application No. PCT/US91/03440), adenovirus vectors (M. Kay et aL, Proc. Natt Acad, Sci. USA, 91:2353 (1994); S. Ishibashi et at., J. 5 Clin. Invest., 92:883 (1993)), or other viral vectors, e.g., various poxviruses, vaccinia, etc.. Recombinant viral vectors, such as retroviruses or adenoviruses, are preferred for integrating the exogenous DNA into the chromosome of the cell, Another subject of the invention relates to a method for producing antibodies, 10 characterized by the following steps: (a) administering an effective amount of the composition according to the invention and/or at least one protective peptide according to the invention to an animal; and (b) isolating the antibodies produced by the animal in response to the administration of step (a) from the animal. 15 A further subject of the invention relates to a method for producing antibodies, characterized by the following steps: (a) contacting a B cell with an effective amount of the composition according to the invention and/or at least one protective peptide according to the invention; 20 (b) fusing the B cell of step (a) with a myeloma cell to obtain a hybridoma cell; and (c) isolating the antibodies produced by the cultivated hybridoma cell. Also included in the scope of the invention is the production of antibodies against a peptide or composition according to the invention. This includes, for example, monoclonal and 25 polyclonal antibodies, chimeric, single chain, and humanized antibodies, as well as Fab fragments, or the product of a Fab expression library, which are able to specifically bind to the peptide or composition according to the invention. In a preferred embodiment the antibody is a monoclonal, polyclonal, chimeric or 30 humanized antibody or functionally active fragment thereof. In another preferred embodiment the functionally active fragment comprises a Fab fragment. Antibodies generated against the peptide or composition according to the invention can be obtained by direct injection of the peptide or composition according to the invention into -34 an animal or administering of the peptide or composition according to the invention to an animal, preferably a non-human. The antibody so obtained will then bind the peptide or composition according to the invention. Such antibodies can then be used to isolate reactive antigens, peptide or proteins from a tissue expressing those. For preparation of monoclonal antibodies, any technique known in the art, which provides antibodies produced by continuous cell line cultures, e.g. a hybridoma cell line, can be used, 10 Techniques described for the production of single chain antibodies (U. S. Patent No. 4,946,778) can be adapted to produce single chain antibodies to the antigenic peptides or compositions according to the invention. Also, transgenic mice or other organisms such as other mammals may be used to express humanized antibodies to the antigenic peptides or compositions according to the invention. 15 Antibodies may be also produced using a hybridoma cell line. Hybridoma cell lines expressing desirable monoclonal antibodies are generated by well-known conventional techniques. The hybridoma cell can be generated by fising a normal-activated, antibody producing B cell with a myeloma cell. In the context of the present invention the 20 hybridoma cell is able to produce an antibody specifically binding to the antigenic peptide or composition according to the invention. Similarly, desirable high titer antibodies are generated by applying known recombinant techniques to the monoclonal or polyclonal antibodies developed to these 25 peptides/proteins/compositions (see, e.g, PCT Patent Application No. PCT/GB85/00392; British Patent Application Publication No. GB2188638A; Amit ot al., Science, 233:747 753 (1986); Queen et al., Proc. Natl. Acad. Sci. USA, 86:10029-10033 (1989); PCT Patent Application No. W090/07861; Ricchmann et al., Nature, 332:323-327 (1988); Huse et al., Science, 246:1275-1281 (1988)). 30 Particularly, the antibody may be produced by initiating an immune response in a non human animal by administrating a peptide or composition of the invention to an animal, removing an antibody-containing body fluid from said animal, and producing the antibodies by subjecting said antibodies containing body fluid to further purification steps.

-35 Alternatively, the antibody may be produced by initiating an immune response in a non human animal by administrating a peptide or composition, as defined in the present invention, to said animal, removing the spleen or spleen cells from said animal and/or 5 producing hybridoma cells of said spleen or spleen cells, selecting and cloning hybridoma cells specific for the peptide or composition according to the invention and producing the antibody by cultivation of said cloned hybridoma cells. Alternatively, the antibody may be produced employing a phage display antibody library. 10 The method is based on the selective binding of one or more members of a phage display antibody library to a surface-bound antigen. The method may e.g. be carried out as follows: an antigen of choice is immobilized to a solid surface, such as nitrocellulose, magnetic beads, a column matrix or, the most widely used, plastic surfaces as polystyrole tubes or 96-well plates. The antibody phages are incubated with the surface-bound antigen, 15 followed by thorough washing to remove the excess nonbinders. The bound antibody phage can subsequently be eluted and e.g. amplified by infection of Escherichia co/i. This method allows the detection of a single antibody phage and as it can be selected by e.g. its resistance marker, it can give rise to a bacterial colony after elution. The isolation of antibodies using phage display antibody libraries has been described in more details by 20 Mancini et at., New Microbiol. 2004 Oci;27(4):315-328 and Pini et al., Curr Protein Pept Sci. 2004 Dec;5(6):487-496. In a preferred embodiment the antibodies produced according to a method of the invention are additionally purified. Methods of purification are known to the skilled artisan. 25 The antibody may be used in methods for treating an infection. Accordingly, still another subject of the invention relates to a pharmaceutical composition, especially a vaccine, comprising the antibody produced according to the invention, The pharmaceutical composition may encompass further components as detailed above. The composition may 30 further encompass substances increasing their capacity to stimulate T cells. These include T helper cell epitopes, lipids or liposomes or preferred modifications as described in WO01/78767. Another way to increase the T cell stimulating capacity of epitopes is their formulation with immune stimulating substances for instance cytokines or chemokines like - 36 interleukin-2, -7, -12, -18, class I and 11 interferons (TFN), especially 1FN-gamma, GM CSF, TNF-alpha, flt3-igand and others. Another subject of the invention relates to a mixture of antibodies against the at least two 5 proteins of the composition according to the invention and/or against the at least one protective peptide according to the invention. The mixture of antibodies may be further characterized and produced as described above. Methods of producing antibodies, mixtures of antibodies, as well as the use of antibodies 10 are also described in Examples 4 and 5, and Figures 4, 8, and 10 to 13. Another subject of the invention relates to the use of the composition according to the invention and/or at least one protective peptide according to the invention and/or one or more of the nucleic acid(s) according to the invention for the manufacture of a medicament 15 for the immunization or treatment of a subject, preferably against S. agalactiae, more preferably against pneumonia, septicemia, meningitis, fever, vomiting, poor feeding, irritability, urinary tract infection and/or vaginal infection caused by S. agalactiae. The peptides, proteins, compositions or the nucleic acids of the invention are generally 20 useful for inducing an immune response in a subject. The vaccine used for immunization may be administered to a subject susceptible to infection by S. agalactiae, preferably mammals, and still more preferably humans, in any conventional manner, including oral, topical, intranasal, intrarnuscular, intra-lymph node, intradermal, intraperitoneal, subcutaneous, and combinations thereof, but most preferably through intramuscular 25 injection. The volume of the dose for intramuscular administration is preferably up to about 5 ml, still more preferably between 0.5 ml and 3 ml, and most preferably about I to 2 ml. The volume of the dose when subcutaneous injection is the selected administration route is preferably up to about 5 ml, still more preferably between 0.5 ml and 3 ml, and most preferably about I to 2 ml. The amount of substance in each dose should be enough 30 to confer effective immunity against and decrease the risk of developing clinical signs resulting from S. agalactiae infection to a subject receiving a vaccination therewith. Preferably, the unit dose of protein should be up to about 5 pg protein/kg body weight, more preferably between about 0.2 to 3 pg, still more preferably between about 0.3 to 1.5 pg, more preferably between about 0.4 to 0.8 pg, and still more preferably about 0.6 jig.

-37 Alternative preferred unit doses of protein could be up to about 6 ptg protein/kg body weight, more preferably between about 0.05 to 5 pg, still more preferably between about 0.1 to 4 pg. The dose is preferably administered I to 3 times, e.g. with an interval of I to 4 weeks. Preferred amounts of protein per dose are from approximately I pg to 5 approximately I mg, more preferably from approximately 5 pg to approximately 500 pg, still more preferably from approximately 10 pg to approximately 250 pg and most preferably from approximately 25 pg to approximately 100 Pg. In still another aspect of the invention the mixture of antibodies or the antibody produced 1o according to the invention or functional fragment thereof is used for the manufacture of a medicament for the treatment of an infection, preferably a S. agalactiae infection. The treatment involves administering an effective amount of the antibody to a subject, preferably a mammal, more preferably a human. Thus, antibodies against the peptides or the composition of the present invention may be employed to inhibit and/or treat 15 infections, particularly bacterial infections and especially infections arising from S. agalactiae. An "effective amount" of peptides, proteins, compositions or the nucleic acids of the invention or an antibody produced according to the invention. may be calculated as that 20 amount capable of exhibiting an in vivo effect, e.g. preventing or ameliorating a sign or symptom of infection, particularly S, agalactiae infection. Such amounts may be determined by one of skill in the art. Such a substance may be administered in any conventional manner, including oral, topical, intranasal, intramuscular, intra-lymph node, intradermal, intraperitoneal, subcutaneous, and combinations thereof, but preferably 25 intramuscularly or subcutaneously. However, it may also be formulated to be administered by any other suitable route, including orally or topically. The selection of the route of delivery and dosage of such therapeutic compositions is within the skill of the art. Treatment in the context of the present invention refers to both therapeutic treatment and 3 prophylactic or preventive measures, wherein the object is to prevent or slow down (lessen) the targeted pathologic condition or disorder. Those in need of treatment include those already with the disorder as well as those prone to have the disorder or those in whom the disorder is to be prevented.

- 38 Another subject of the invention relates to a method of diagnosing a S. agalactiae infection comprising the steps of: (a) contacting a sample obtained from a subject with the composition according to the invention and/or at least one protective peptide according to the invention; and 5 (b) detecting the presence of an antibody against the protective peptide, the fictionally active variant and/or the composition in the sample, wherein the presence of the antibody is indicative for the S agalactiae infection. Another subject of the invention relates to a method of diagnosing a S agalactiae infection 10 comprising the steps of: (a) contacting a sample obtained from a subject with the mixture of antibodies according to the invention; and (b) detecting the presence of the at least two proteins of the composition according to the invention and/or of the at least one protective peptide according to the invention in 15 the sample, wherein the presence of the at least two proteins and/or of the at least one protective peptide is indicative for the S. agalactiae infection. The protective peptides or compositions of the invention or alternatively a mixture of 20 antibodies may be used for the detection of S. agalactiae. Preferably such detection is for diagnosis, more preferably for the diagnosis of a disease, most preferably for the diagnosis of a & agalactiae infection. The protective peptides or compositions may be used to detect the presence of a & agalactiae-specific antibody or fragment thereof e.g. in a sample obtained from a subject. Alternatively, the mixture of antibodies may be used to detect the 25 presence of S. agalactiae proteins, e.g. in a sample obtained from a subject. The sample may be e.g. a blood sample. The present invention also relates to diagnostic assays such as quantitative and diagnostic assays for detecting levels of the proteins, compositions and/or mixtures of antibodies of 30 the present invention in cells and tissues or body fluids, including determination of normal and abnormal levels. Assay techniques that can be used to determine levels of a peptide, a composition or an antibody, in a sample derived from a host are well known to those of skill in the art. Such assay methods include radioimmunoassays, competitive-binding assays, Western Blot analysis and ELISAs. Among these, ELISAs frequently are preferred.

-39 An ELISA. initially comprises preparing an antibody or antibodies specific to the peptide or composition, preferably a monoclonal antibody. In addition, a reporter antibody generally is prepared which binds to the monoclonal antibody. The reporter antibody is attached to a detectable reagent such as radioactive, fluorescent or enzymatic reagent, such as 5 horseradish peroxidase enzyme. The peptides or compositions of the present invention may also be used for the purpose of or in connection with an array, More particularly, at least one of the peptides or compositions of the present invention may be immobilized on a support. Said support Io typically comprises a variety of peptides/proteins whereby the variety may be created by using one or several of the peptides or compositions of the present invention. The characterizing feature of such array as well as of any array in general is the fact that at a distinct or predefined region or position on said support or a surface thereof, a distinct polypeptide is immobilized. Because of this any activity at a distinct position or region of 15 an array can be correlated with a specific polypeptide. The number of different peptides or antibodies of the present invention immobilized on a support may range from as little as 10 to several 1000 different peptides or compositions of the present invention. Alternatively, antibodies produced according to the present invention may be used to detect peptides or compositions of the invention. 20 The manufacture of such arrays is known to the one skilled in the art and, for example, described in US patent 5,744,309. The array preferably comprises a planar, porous or non porous solid support having at least a first surface. Preferred support materials are, among others, glass or cellulose. It is also within the present invention that the array is used for 25 any of the diagnostic applications described herein. Apart from the peptides or antibodies of the present invention also the nucleic acid molecules according to the present invention may be used for the generation of an array as described above. Another subject of the invention relates to a method for diagnosing an infection with S. 30 agalactiae comprising the steps of: (a) contacting a sample obtained from a subject with a primer and/or a probe specific for the one or more nucleic acid(s) according to the invention; and (b) detecting the presence of one or more nucleic acid(s) according to the invention in the sample, - 40 wherein the presence of the one or more nucleic acid(s) is indicative for the S. agalactiae infection. A series of methods for detecting nucleic acids in samples by using specific primers and/or 5 probes is known in the art. In general, these methods are based on the specific binding of a primer or probe to the nucleic acid in question. The methods may involve amplification of the nucleic acid, e.g. RNA or DNA, before the actual detection step. Therefore, primers may be used to specifically induce transcription and/or amplification of RNA or DNA in order to generate a detectable amount of nucleic acid. Suitable well known techniques may Jo be PCR and RT-PCR. Suitable primers and probes for the method of the invention may be produced based on sequence information provided in the present application. Guidelines and computer-assisted programs (e.g Primer Express*, Applied Biosystems, Foster City, CA, USA) for designing primers and probes to a specific nucleic acid are known to the person skilled in the art. 15 After the amplification step the amplified nucleic acid, in general DNA, may be detected e.g. by its size (e.g. involving agarose gel electrophoresis) or using labeled probes which specifically bind to the amplified nucleic acid. The probes may be labeled with a dye, radioactive marker, a fluorescent marker, an enzyme-linked marker or any other marker, 20 For example, FRET (Fdrster resonance energy transfer) may be used for the detection of the nucleic acid of the invention. In FRET, a donor fluorophore molecule absorbs excitation energy and delivers this via dipole-dipole interaction to a nearby acceptor fluorophore molecule. This process only occurs when the donor and acceptor molecules are 25 sufficiently close to one another, Several different strategies for determining the optimal physical arrangement of the donor and acceptor moieties are known to the skilled practitioner. For this, a fluorescent donor is excited at its specific fluorescence excitation wavelength. By a long-range dipole-dipole coupling mechanism, this excited state is then nonradiatively transferred to a second molecule, the acceptor. The donor returns to the 30 electronic ground state, The described energy transfer mechanism is termed "Fdrster resonance energy transfer" (FRET). The process involves measuring fluorescence as FRET donor and acceptor moieties are brought together as a result of DNA hybridization. For examples two probes each labeled with a suitable marker hybridize to the nucleic acid of the invention within a distance which allows FRET to occur. Suitable markers include -41 Cyan 500, Cy5, Cy3, SYBR Green 1, fluorescein, HEX, Red 610 and Red 640, wherein the two marker involved have to be selected based on there excitation and emission spectrums as known by the skilled person. A suitable system for the detection of nucleic acids is the LightCycler" (Roche Diagnostics). 5 Another subject of the invention relates to a method for identifying a ligand capable of binding the composition according to the invention and/or at least one protective peptide according to the invention comprising: (a) providing a test system comprising the peptide and/or composition, 10 (b) contacting the test system with a test compound, and (c) detecting a signal generated in response to the binding of the test compound to the peptide and/or composition. More particularly, the method may be carried out by contacting an isolated or immobilized protective peptide or composition according to the invention with a candidate ligand under 15 conditions to permit binding of the candidate ligand to the peptide, wherein the test system comprises a component capable of providing a detectable signal in response to the binding of the candidate ligand to said peptide; and detecting the presence or absence of a signal generated in response to the binding of the ligand to the peptide. The ligand may be an agonist or an antagonist. 20 Test systems for detection binding of a ligand are known to the skilled artisan and include e.g. binding assays with labeled ligand such as radioligands, fluorescence-labeled ligands or enzyme-labeled ligands. 25 The test compound can be any test compound either naturally occurring or chemically synthesized. Naturally occurring test compounds include in particular antibodies, preferably those showing similarity to the antibodies of the invention, In one preferred embodiment of the invention the test compound is provided in the form of a chemical compound library. Chemical compound libraries include a plurality of chemical 30 compounds and have been assembled from any of multiple sources, including chemically synthesized molecules and natural products, or have been generated by combinatorial chemistry techniques. They are especially suitable for high throughput screening. They may be comprised of chemical compounds of a particular structure or compounds of a particular creature such as a plant.

- 42 A further subject of the invention relates to the use of the composition according to the invention and/or at least one protective peptide according to the invention for the isolation and/or purification and/or identification of an interaction partner of the composition and/or 5 peptide. The isolation and/or purification and/or identification of the ligand may be carried out as detailed above or as known to the person skilled in the art. In a preferred embodiment of the invention an affinity device may be used. The affinity device may comprise at least a support material and any antigenic peptide or composition according to the present invention, which is attached to the support material. Because of the specificity 10 of the protective peptides and/or compositions according to the present invention for their target cells or target molecules or their interaction partners, the peptides and/or compositions allow a selective removal of their interaction partner(s) from any kind of sample applied to the support material provided that the conditions for binding are met. The sample may be a biological or medical sample, including but not limited to, 15 fermentation broth, cell debris, cell preparation, tissue preparation, organ preparation, blood, urine, lymph liquid, liquor and the like. The peptide or composition may be attached to the matrix in a covalent or non-covalent manner. Suitable support material is known to the one skilled in the art and can be selected from the group comprising cellulose, silicon, glass, aluminium, paramagnetic beads, starch and dextrane. 20 The present invention is further illustrated by the following Figures, Examples and the Sequence listing, from which further features, embodiments and advantages may be taken. It is to be understood that the present examples are given by way of illustration only and 25 not by way of limitation of the disclosure. FIGURE LEGENDS 3o Figure 1 shows the protection achieved by passive immunization with selected hyper immune rabbit sera generated by immunization of rabbits with S. agalactiae antigens in a mouse lethality model. CD-1 mice (10 mice per group) were immunized intraperitoneally with 150 pl hyper-immune rabbit sera 1 - 3 hours before they were intraperitoneally challenged. (A) gbsi309p, gbs1478p, gbs2018p, Sip and PBS-induced hyperiumune sera, - 43 challenge with I x 107 efu C388190 serotypee Ia/c). (B) gbs1478p, gbs 2 0 I8p, Sip and PBS induced hyperimmune sera, challenge with 5 x 106 efu ATCCI2401 serotypee lb). (C) gbs0233p, gbsiO87p, gbsl477p, Sip and PBS-induced hyperimmune sera, challenge with I x 10 cfu ATCCI2403 serotypee 111). (D) gbs0233p, gbslO87p, gbs2018p, Sip and PBS 5 induced hyperimmune sera, challenge with I x 10 cfu ATCC49447 serotypee V). Survival was monitored for 14 days post-challenge. Numbers of surviving mice are plotted as percentage of total mice. Figure 2 shows the protection achieved with a combination of & a,(galactiae antigen 10 specific hyperimmune rabbit sera in a mouse lethality model. CD-i mice (10 mice per group) were immunized intraperitoneally with different combinations of hyperimmune rabbit sera (150 pl per hyper-immunc rabbit scra) I - 3 hours before an intraperitoncal challenge. Sip- and PBS-induced sera were used as positive and negative controls, respectively, Mice were immunized with combinations of sera induced by gbs1O87p, 15 gbsl477p, gbsi478p and gbs2018p; challenge with (A) 5 x 106 cfu ATCCI2401 serotypee Ib); (B) I x 10a efu ATCC12403 serotypee TI!) and (C) I x 108 efu ATCC49447 serotypee V). Survival was monitored for 11 days post-challenge. Numbers of surviving mice are plotted as percentage of total mice. 20 Figure 3 shows the surface staining of the serotype III GBS strain ATCCl2403. The results for the hyperimmune rabbit sera (black) are shown in comparison to those for the respective preimmune sera (white). Figure 4 shows an opsonophagocytic killing assay with hyperimmune rabbit sera and 25 different GBS strains. (A) Serotype 11 GBS strain AC3912, not suitable for animal testing, (B) Serotype V GBS strain BAA23, used for animal testing. PI, preimmune sera; HI, hyperimmune sera. GBS cells in the exponential phase were opsonised with 200-fold diluted sera in the presence of 5% guinea pig complement for 60 minutes. Phagocytic cells (RAW264.7) were added to opsonised bacteria and incubated for an additional 60 minutes 30 at 37*C. Surviving bacteria were counted on agar plates after overnight incubation at 37 0 C. Percentage of killing was calculated based on CPU obtained after incubation with the different hyperimmune sera relative to CFU obtained with preimmune sera at 0 min and after 60 min of incubation as described under experimental procedure.

- 44 Figure 5 A-D show the sequence alignment of protein sequences homologous to gbs1477 from genomic and sequenced strains. Alignment of sequences was performed using the software from Vector NTl (Suite 7.1; Invitrogen, Austria). The name on the left of the sequence indicates the strain name, Amino acids in bold, residue identical in at least 50% S of sequences. *, indicates position of STOP codon, Figure 6 shows active protection of adult mice by immunizing with a combination of GBS antigens. CD-1 mice (10 mice per group) were immunized with different combinations of the recombinant proteins (gbslO87p, gbsI477p, gbs1478p and gbs2018p; 25 pg each). As 10 positive control 25 pLg Sip protein (open circle) was used. For the negative control, PBS (open square) was used with ALUM 1%. One week after the last booster immunization, mice were challenged with (A) 3.5 x 106 cfu 12401; (B) 8.8 x 107 efh 12403 or with (C) 1.1 x 1IV cfu 49447. Numbers of surviving mice are plotted as a percentage of the total number of mice. 15 Figure 7 shows active protection of adult mice by immunizing with single GBS antigens. CD-1 mice (10 mice per group) were immunized with different recombinant proteins (gbs0233p, gbsi107p, gbsl309p, gbsl477p, gbsl478p and gbs2018p; 50 gg each). As positive control 50 pg Sip protein (open circle) was used. For the negative control, PBS 20 (open square) was used with ALUM 1%. One week after the last booster immunization, mice were challenged with (A) 3.5 x 106 cfu 12401; (B) 8.8 x 10 7 efu 12403 or with (C) 1.1 x 10 cfu 49447. Numbers of surviving mice are plotted as a percentage of the total number of mice. 25 Figure 8 shows the protection of neonatal mice by immunization of mothers passively with rabbit sera generated with a combination of recombinant GBS antigens. Pregnant CD I mice were immunized at day 18 post gestation with 500 pA of combinations of gbs1087p, gbsi477p, gbsl478p and gbs2018p-induced sera or PBS-induced control sera. Neonates were challenged within 24 - 38 hours after birth with lethal challenge doses of (A) 1.2 x 30 107 cfu C388/90; (B) 1.3 x 106 cfu 12403; (C) 5.7 x 10 efu BAA23 or (D) 1.8 x 10" efu 2603VIR. Numbers of surviving neonates are plotted as a percentage of the total number of challenged neonates.

- 45 Figure 9 shows active protection of adult mice by immunizing with different clade gbs1477p proteins. CD-I mice (10 mice per group) were immunized with different clade proteins of gbsl477p (gbs1477p-2603V/R, gbs1477p-49447, gbsl477p-C388/90, gbs1477p-126H4A and gbs1477p-NEM316; 50 Ig each). As negative control, PBS (open 5 square) was used with ALUM 1%, One week after the last booster immunization, mice were challenged with (A) 1.4 x 107 efu C388/90; (B) 1 .2 x 108 cfu 12403 or with (C) 1.6 x 10 cfu BAA23. Numbers of surviving mice are plotted as a percentage of the total number of mice. 10 Figure 10 shows the protection of adult mice by immunization with mouse mAbs against different recombinant GBS antigens. CD-I mice were immunized intraperitoneally with 50 pg of the respective mouse mAb. I to 3 hours later, mice were challenged intraperitoncally with (A) 1.2 x 10 efu 12403; (B) 1.5 x 108 cfu 12403 or (C) 1.1 x 108 efu 49447. Numbers of surviving mice are plotted as a percentage of the total number of challenged mice. Figure 11 shows the protection of adult mice by immunization with a combination of five mouse mAbs against different recombinant GBS antigens. CD-1 mice were immunized intraperitoneally with 25 jig of each mouse mAb. I to 3 hours later, mice were challenged intraperitoneally with (A) 1.2 x 107 cfu C388/90; (B) 9.6 x 10 cfu 12403 or (C) 1.7 x 108 20 cfu BAA23. Numbers of surviving mice are plotted as a percentage of the total number of challenged mice. Figure 12 shows surface staining of the serotype III GBS strain ATCCI2403. The results for the monoclonal antibodies (black) are shown with the buffer control (white). 25 Figure 13 shows opsonophagocytic killing assay with hyperimmune rabbit sera and different GBS strains. Rabbit sera were tested in the opsonophagocytic killing assay at a scrum dilution of 1:1,000, % killing was calculated in relation to the respective pre immune sera. The mouse monoclonal antibodies were tested with two different amounts 30 added to the opsonophagocytic killing assay, 1.0 and 0.1 pig. The % killing for the monoclonal antibodies was calculated in relation to the complement control.

EXAMPLES

-46 Example 1: Group B streptococcal antigens and combinations thereof inducing protective immune responses against lethal sepsis in an i.p. challenge model. 5 Experimental procedures Cloning and expression ofrecombinant Group B streptococcal proteins Cloning of genes: The gene of interest was amplified from genomic DNA of S. agalactiae 1o ATCCI2403 serotypee Ill) by PCR using gene specific primers. Apart from the gene specific part, the primers had restriction sites that aided in a directional cloning of the amplified PCR product. The gene annealing (specific) part of the primer ranged between 15-30 bases in length. The PCR products obtained were digested with the appropriate restriction enzymes and cloned into the pET28b (+) vector (Novagen) for His-tagged is proteins. Once the recombinant plasmid was confirmed to contain the gene of interest, Z coli BL21 star cells (Invitrogen) that served as expression host were transformed. Cloning of the gbsl087, gbs1477 and gbsi 478 genes has been performed using genomic DNA from strain S. agalactiae 6313 (serotype Il1) in the vector pET28a (+).The origin ofthe gene and position within the full length gene of the selected antigens are listed in Table 1. The 20 amino acid and nucleic acid sequences are as follows: Amino acid sequences: SEQ ID NO: 1 25 Construct 1: gbs0233p LCLALLTISGCQLTDTKKPGHTTI KVAAQS STERSSIMANIV \TELT i-IEELGYNTTLI SNLGS STVTHQALLRGDADIAATRYTGTDITGTLGLKAVKDTKEASKIVKTEFQKRYNQTWYPTYG FSDTYAFMVTKEFARQNKITKIS DLKKLSTTMKAGVDSSWMtNREGDCYTDFAKTYGFE PSH IYPMQIGLVYDAVESNKMQSVLGYSTDGRISSYDLEILRDDKKFFPPYEASMVVNNSIIKK 30 DPKLKKLLHRLDGKINLKTMQNLNYMVDDKLLEPSVVAKQFLEKNHYFRGD SEQ ID NO: 2 Construct 2: gbs1O87p MDSVGNQSQGNVLERRQR DAEN RSQGNV:LERRQRDVENKSQGNVLERRQR DAENKSQGNVL 35 ERRQRDAENRSQGNVLERRQRDAENRSQGNVLERRQRDAENRSQGNVLERRQRDAENR QG NVLERRQRDAENRSQGNVLERRQRDVENKSQGNVLERRQRDAENKSQGNVLERRQRDAENR SQGNVLERRQRDAENRSQGNVLERRQRDAENRSQGNVLERRQRDAENRSQGNVLERRQRDA ENRSQGNVLERRQRDAENRSQGNVLERRQRDAENRSQGNVLERRQRDAENRSQGNVLERRQ RDAENKSQVGQLIG 40 SEQ ID NO: 3 -47 Construct 3: gbslSO9p SVTY SQSERTV"VFSEETTFSRSPWTNCFETRT PVDEWLCLEKYKRYS TEFLYHV ,.AKLATM M-PYF{QVCKV IDS TLQTIITKDCVLKAVKE"JKVEKLLKEKERYREY LEE PPERKKVKKLYVECD CVPT)lKSTDSREERRYLDLTHFVT HTCSKKVSTKRYELQDKEE ILQTJNYDKAKYNLLDY IYN 5 NYEVDDDTT LITNSDMC'iKCYvTSRVFKELCKALKVKKUEHEWDTYH-VKEKLSSYLRKYPTEL T D FALDAVKKYN SDKELVFDT E SD TO DEILE QE F'QKE'KKK.VLNN ThY I KPAILEINLSNR CICTMESQHPKITYRKRMYWSKWCTSTMAIMT TLERANC .LRELEECSWEKVYSEYKEC SES;--ACRLFKKTDELDKFSKPLLKNCRKWS ITGIK 10 SEQ ID NO: 4 Construct 4: gbsl47lp DDVITDTIVT LEN I VM PQAAF D NFTE CGT KCKND'ISDYVCI KQ ?-I DTJKS YFCS T DANE I KCAFTv FKNETGTKI TENCKEVDTLEAKDAECCAVLSGLTKDTCF&AFNTAKLKCTYQIVELKEKSN YD NNO SI LADSKAVPVK ITL PLVNNQCVVKDAII fPKNTE TK PQVDKNELADKDLDY TDNRK 15 DKCVVSATVGDKKEY TVC TKTILC S DYKKLVWT DSNTKCLTFNWWVKVTLDGKDFPVLWYK LVT DDQCFRLAL NATTAAVlAAAKDKDVETI KITYSATVNOSTTVRVPETN DVKLDYCWNP TEE SE PQEC-T PANQE 1KV1K DNAVDCTITTDVNVAVKAT FTLQEKQT DOTWVNVAS HEATNE SRFENTETGLDNTKTYRV VERVSCYTPEYVS FKNG'VVT IKNNKNSNDPTPINPSEPKVVTY CJRKF'VKTN'iQAN T ERLACAT F'LVKKEC.'KYLARKAC.AATAE'AKA;AVKTAKL AL D]EAVKAYN4 DLt 20 TKEKQECQECK4TLATVD QKQK.AYN DAFVFKANY SYEWVADKKADWVVKLI SWACCQFE ITC LDKCTY SLEETQAPACYATLSCDVNEEVTAT SSSKCATT D AY DROSVKKDAQQVQNKKVT I PQTCCIT SEQ ID NO: 5 25 Construct 5: gbsl47Sp ES TVPENGA KGKLVVKKTDDQNKPL"S KAT E'VLKITAI FE 5K £KVTAI.'T CjEATE-'DNLI PG DYTLSEETA PECYKKTNQTWQVKVESNGKTTTQNSGDKNSTTCQNKEEL3DKQYPPTGIYED TKESYKLEHVKCSV PNCKSEAKAVNPYSSECEETRET PEGTLSKRTSEVCDLAHNKYKIEL T'VS SKI IVK FSKQKPL DVVFVLDWSN SIEWN DGPLFQRHNKAKK-APAALTAVKD I CAWS 30 DNRVALVTYGS DI FDCRSVDVVKGFKE-DD KYYCLQTKFT T.QTE'NYSHfKQ~zLTWNAEEI ITKRI11 PTEAPRAKWCSTTNCLTPEQQKQYYLSKVCETFTMKAENEADDTLSQVDRNSQKI IVETTD C-VPTRSYAT NNEKLCUASYESQEEQMKKNGYLN KSNELLTD. ''[KPEI.K.(3NCE'Q YE , i PI, DSYQ TQI ISCWLQKTA-YLDLLNYPKGTIYRNGPVREHGTTKLYINSLKQKNYDTFNECIDISA FRQVYNEDYKKWQDCT-FQKLKEEAFELSDC"E ITELMKS ESSKPEYYTPIVTSSDASNNETL 35 SKI QQQEEKVLTKENS TVNCT 4IEDPMC-DKT WLQLGWCQTLQPS DYTLQCWDCS TENDSI TAT, C-GPNWDCC I LKGVKLEY T"KNKLYVRCGLNLCEC,'QKVT E'TY DVKLD)DSFT SNKF'YDTNCGRTTL NPKSEDPWTLRDEPI PNIRDVREYPTTTINEKNLGETEFTKVDKDNNKLL7LKCATFELQE ENEDYKIYLP IKNWWSK'VVTGE NCKI SYKDLKDCKYQLTEAVS PKDY-QKTNKPT LTEEVV KCS TONI IAV NKQIS-EYPiEEGDiKHITW ,THI PPKGI I PNTCCIJK 40 SEQ ID NO: 6 Construct 6: qbs2Ol8p DTSSCTSASIP24KNQVNLCATL TKNLISNYRGNDKATATLLSRVNDFNRASQDTLPQLTWNS TEAEIRNILYQCQTCKQNKPSVTTHAKVSDQELCKQSRRSQDITKSLCEIJSSDQKDTLVNS 45 IS SSKDSQLI LKPVTQATQLW-NAESTKAKQIAQND)VALT'KWT -S !TVLEE-YNE:K IQRASTIKS QVDE EVAEAKKVVWSNKETLVNQANKQE I ANLEWLSWDEMLRYNTA IDNVVKQYWECKL N--IAMNtALNSTKQAAQEVAQKNLQKQYA' KKERISSKGLALSKAPKEIYEKHKSILPTPC YYATDS VCTYLNRERDKQT FGNRS VWTCUQS CLDEAKNMLDEVNNLLKELQDULTRCTKE DKKP DVKPEAKPE AK 2W :E:QVPKQPTEAAKPALS PEALTRLTTWYNQAKDLLKD-DQVKDKYVDI I 50 AVQKAV DQAY DI-VEECKT T TDQAN4QIANNIDKRDALQS IEKDKKVAT(PEA KPEAKPEAKPE AK PEAK PIAKPEAT4PEAKP DVKPEA KPDVKPEAKPEAK PEAKSEAKPEAz KI"EAKPEA KPAT KKSVNT SGNLA-AKKA I ENEKY SKKL PS T Nucleic acidscicc: 5 SEQ ID NO: 7 Construct It gbsO2S3p CTTTGCTTAGCCCTCTTAACC3ATTTC"TGCCTTGTC-AATTAACCGATAC"TAAAA'ACCTGGTC ATACCAO~AATTAACGTTCC-TCCCAAAGT TO TACAkCAGCTACTATCATCGCAAATATTCT CAC'CCAATT A TT CATCACGAAT TKGGATACAACAACT T TAATAAGCAAT CTTOCGT TCO 10 TOTACGGTTACTCACCAAG..CTTTGCTCCGTGGTGATGCTGACATTGC-TGCCACACGTTATA CAG'GAAC,,AGAO-ATOACA.GG'A-AC TO TT"GGC T TAAAAGC TGT TAAAGA'CO TAAAGAAGC TT.C TTTTCTGATA"TPTATG.CATTATGGTTACTAAAGAGTTTGCC"ACA CAGAATAAAA -TCACCA AGATOTCTGATCTC-PAAAAGT TATCAACAAG TATGAA-GGOA GGG3TTGATAGT TOATO-GAT 15 G-AATCGC( (GAGGGAG3ATGrGATACAG.TGA.TTC GC'TA.AAO(-ATACGGT3-TT TGA-ATTT TCACAT AT TTACOO CTAT GCA-AAT TGO TTAG T CTAT GAT GC AGT TGAAAG TAACAAo-AAT GOAATOCTCG TAT TAGGO TAC-TCC-ACTIGAOGGTCGTAT TTCGAGC TATGATTTAGAAATTTTAAZGGGATGA Tki AAiAT TOTTT,-C r'CCT~ATGAArCC TO T.ATGGTTGTOAAC.AATTC TATCATOAA7-AAA' GATCC TAACTAAAAAATTAO TCOATCGAC TCGATGGTAA-AATC-AAkT TTAAAAAO GATGC 20 AAAACCTTAATTATATGGTAGATGATAAA,'CTTTTAGAAOC-TTCASTTGTTGCOAAACAA'TT TTTAGAAAAAAOC.2-"TmATTTTAGAGGAGAT SEQ ID NO: 8 Construct 2: qbs1087p 25 AT-GGATAC-TGTT-GGAAATCAAAGTCAGGGC-AATGTTT G-AGCGTOGTCsAOCGTGATGO-JAG AAA-TACAGAA ,GCCAAGGOAATGTTOTAGAGOGTCGTCAACGCGATGT TGAGAATAAGAkGCCA AG GCAAT GT TT T AGAG.:CGTC G TAACG TGAT GC GGAAAACAAGAGCOCAAG GCAAT G T TT TAi G3AGOGTCGTCAACGTGATGCAGAAA, ACAGAAGCAAGGCAkATGTTC TAGAGOG2TCGTC A AO GT-GAT-GCAG-;1,AAA2CAGAAPGCCAAGGCAA TG-T TOTAGAGCGTCGTCAAC-GCG ATGCAGAA . 30 CAr-C4AAGCAAGGTAATG.TTCTAGAGCGTCGT CACGTGATGC-AGA-AAACAkGAAGCCAAGG-T ,AJ TT CiTA GAGCGTOCTG'CAACGE.IGATIGCAGAAACAGA&GCCAAGGP'AAC T TOTAG',AGO G TCGTC"AAC GC GATCG-T TGA"GAA TAAGAGCC.AAGGC AAT GT T T TAGAGC-G TCG TOAAG T GA TGO GGAAA ACAAGAGC CAAG GOAAT GTTT TAGAGOGT C GTCAAG.GT GAT GCAG AAAACAGA AGCOAAGGC-AATGTTTTAGAGCGTCGTCAA CGTGATGOUAGAAAZACAGAAGCAAkGGCAATG 35 TTCTAGAIGC-GTCGTCAAGTGATGC -AGAAAACf-AGAAGOCAAGGCAATG'iT TOT[AGAGCTG'i TCAAOGTGATGOAGAAAOAGAAGOCAAGGCAATGJTTCTAGAGCOGTCGTCA' ACGCGATGOA~i GAAPi..AACAGAAGCCA.'PAGGTAATGTTCTAGAGCGTCGTCAPACGTGATGCAGAAAAOAGAAGOC AAkGGCAATGTTTTAGAGCGTOGTCAAkCGTG-ATGCAGAAAZACGAAGCC-AA -GGCAiATGTTTT- AGAG-CGTCGTCAA;CGTGATGCAGAAA ACAGAAGCCAA4GGCAAkTGTTT TAGA GC-GTOGTOAA 40 C-GTGIATGCGGAAAACAAGAGCGAAG-TAGGTCAACT TATAGGG SEQ ID NO: 9 Construct 3: gbsl309p AGTG-TAACOTATTCAOAGTO TG -AAC-GTACGGTT GT TTTCTCTTTTG-GAGAAATPAACATTTA 45 GA" CCGGC-~AGGT-G ACAPTCAGAA ,ATGGTTA GTCT TGAAAkAATATAA-GAGATAT TCAATAGAA1TTCTTATATCATGT TGCAA T-AATTGGCTAOAiATG ATGC"-CT'TATOGTOAAG''TGO(AAAGTAATAGATAGCAOTTTGCA-AACAATCATAAOAA.AAG ACT G TGT TTT M-,AAGC AGTr';AAAAT T TGTAGAAAAATT GT TAAAA.GAAAAk'AAA'(CTATCG'( T TT T-1AT T T GGAAzGAG CCACC GAAOCG T AAAAAAG TG:,AJ~AAc TG-TATG T TGAGGG TCGAT 50) GGAGTC-'-ATGATTiAAAAGOACAGATTOTArPGAGAGG3AAG'AAGG.TA'TT,-AGATT TAACAOAT T TTGT TATTCATACAGGO TC2AA-AAAGT TTCTACTAAAAGATAGAAT TGC'AG'GAC-AAGO'7A -49 C'GAAATAT .TACA'ZGC T TAATTATPGATl.AA2AGCTAA-7,AATAATCT TTTr'~iAG3ATITATi.AT T TATAATi AACT ATOGAAO3T AGA TGACGATACT AT TTTA-ATCAC TAC-TCTG AT AT GGGTAAAGGC T ATA C 'TACTAGA4T TTT TAAGGAATTAGGAMP iGCACT TAAGGTAAAGM.%ACATGAGCATT TiTG GGAT AT-CTATCATGTTAAAGAAAAGTTAACTTCA.TACCTTAGkAAATATCCAATTGAATTA 5 ACCGATTTTGCTTTACATCCGGTA-AAAAAzTATAATTCTCATAAGCTTGAATTA.GTTTTTC ATACTGT TGAATTCAC-TGA'TTTGTGATGA,-AC TTGAy AGATCAPiAGAAT TTCAGAAl-GTT TAAGA.A AAAAGTAT TAA ATAATT TCA.AAT AT ATAA-AACCAGCT CA TC TAGAAATC TTTCAAATCGT Gc3TATTGGT'A.TCA.TGGAAT'CACAACACAGAAAGATAACGT'3iATAGAAT 'IGAAGCC(AC.GTGCC ,A T-1GTATT--GGTCAAA.GTGGGL3AATCTCCA CAA 'TGGCAA-,ATAITG-ATTATACT TGT-AA-GAGCTAAT 10 CGGT",-TTACGAGAATTATTITTTCOGTTCTTGGAGA AAGG3TATACAGTGAGTATAA AGAACGT' TCATTT7ACTGCAGG -CACTTTTTAAAA-AGACAGATGAA-TTAGATAAATTTTCTAAGCCC TTC-TP7AAATGGCAGAAA.TTGGA3TATAACAC3CAA lTCAAA SEQ IV NO: 10 15 Construct 4. gbs1477p GACCIACCTAACAACTG1(-ATA CTCTG(5ACCT T CACAACAT TGT CAT GCCACACCTGCATTTC3 ATPAAC-TTTAC TGA.AGGTA'CPAAAiGGTAAGA ATGAT AGCGAT TATCT TCOTAAkACAAP3T4"A -TCAAUAAATGA-AACTCCTACAAAAPTTCATTAC -TCA-AAATGOTAAt3GAAGTCGATAC-TTT-G 20 AAGCT'AAAGATG3CTG3AAGC TGOCTOCT TTTCT TCAGCTTAACAAAA-GACACTGGTTTT'C TTTTAAGAC TGC TAAGTTAAAAGGAACT TACC CAAATCGTT'GAAT TCTLAAAGAAAAATC-AAALC TACk'-GATAACAACGCTTCTATCTTGGCTGAT-TCA.A2ACAGTTCCACTTAAAACAC C C AT TGT AAACAACCAAGGT GT T GTTAA AGATCCT'," CAC AT T TAT CCArACAAT AC TGAAAC AAAC-CACAAGTAGATAAC--AACT TTCCACATAAXCATCTTGkT TAT.ACTC.%'AC'AACCO'3AAAA 25 CACAP AAGGTGT TGTC-TCACC-GACAGTTGCTGACAAAAAACAATACATAOTTCCAACAAMUA -TTTTAAAGGCTCAGACTATAAGAAA"CTCGTT:GACTGATACCATCACTAACCTTTCAC GTTCAACAACAACGTPTAAAGTIAACATTG-GATGGTAAACAT TTTCCTOT TTTAAACTACAAAk CTC GTAACACATGACCAAGCTTT, CCTCTTCGCCTTC-AATGCAACAGGTCTTGCAGCAOTAG CAC CTCCTGCAAtAAGACA-,AAA"TTTGAAATC(AAGATCAPC TTAC TCAGCTACGCTGAACCGG 30 OTO-CACTAC TGTTGAACT TCCAGAAACCAATGATGTTgAAATGCAC T'ATGGTAATIAA(CCCA ACGGAAUGAAACTGAACCACAAGAAGCTACTCCAGCTAACCAACAAA TTAAA-zGTCAT TAAAG ACTG CCCTACAT-GTACAAJTTACTGATGTTAPATC"TTCCACTTA.AACCTATCTTTACCTT GC-AAGAAA? AACAAAC,-GGATCGTAC ATGGC TGAAC GTTGCTTCACACCAACUCAAzCAATAACCA-l T CACCCTTTCAA,7CATACT TTCACACGTT TCU ATAATACTAAAAC TiACCGCGT T.GTCGAAC 35 GT(3"T-TACCGCCTACACTCC-ACAATATCTATC,-ATTTA~AAAATGCICTTCTC13ACTATCA-AGiAA CAACAAAAAC TCAAATGATCCAAC T.CCAATC,;zA"CC.ATiCAG'AA'zCCAAAAG TC-GTGAC.T TAT GC3ACGTAAAT TTC TG CAAACAAAo-TCA-AGC TAACAC TCAACCCT TGCCAGC-AGCTACCT T-C TiC 3TTAA 2GAA AGAC3GAAA&TAC TTGCCACGTAAACkCAGGTGCAGCAACTCCTGAACCAAAL CCC'AGCTGTA AA.AACOTCTA-AAC TACCATTCC-JATGAACGCTCTTAAAGCTTATAAGGAC TiC 40 AC TAY4AAGAAAAAGG CCALAG AACCGTAA AACAG CAT TGCCTA CT GT TCGA TCAAAAAC IsAAAAACCTTACAATC;ACGCTTTTGTTAA 4AGCT"-AACTACTCATAGAATGCGTTGCAGATFAA AAA.GOCTGATAATGTTCT TAA ATTC3ATC T'CTFAC-G(CGG IGG TC AATTT G AA:-AT TACTCGG T CAGCTGATGTAAAt'CTTTGAAGTAAPCTGCCACATC-ATATAGC-A-AAGGGGCTACAACTGACAT 45 C-;C AT A TGA TAAAG G AT C T GT AAAAAAAC AT G CC CAAC AAG T TC AAAC AAAAAG T AAC C ATC-CCACAAAC.AGGTG;GTA'TT'(3GTACA SEQ ID Not 11 Construct 5: gbsl47Sp 50 GAAGTACGTACC GGAAAATGGTGCTA-, AGGAAAkGT TAGTTGTTAAAA-AGACAGATGAC AGAACA&AAC CAC TT T CAAAAG C TACC T TTGT T T TAAAAAC TAC T GGCT C T C CAG A-AGTAA =5O OAT T--ATACTT' TATOAGAAG', AAACA5000000-CGAOGTTATAArSAGACTAACCAGAGT TGO AOTTAAGGT TGAkGAGTA-ATGGAAA2AACTACGATAOAAZAATAGTGGTGATAAAA'ATTCCAOc AATTGOAOA-TAATGTAOGAAOACTAATAAGCATAT-CCCCCAGGAATTTATGAAGAT 5 ACPAAOGAAkTGTATAZ AOT TOAGGCATGT TPAAOGTTGTTCCAAATGGOAAOTCAG3AGG CAAc~AAGCAGTTA"ACOGATAT TCAAkT GAAqGGTGAOCATATAAGAGAAAVTTCCAGAGGGAA.C ATTATCTAA-iACGTAT TTCA-GAAGTAk-GGATTTAOO TCATAATAAAkTATAM-AATTGAOTTA ACTOTC AGTOO3GlAAACCAT-AGTlAAACCA OTGGAOAAACAAAAGGOGT TAGATGOT G~~T TCGTACTGGATAATTG TAAGTGAATGA.ATAAGATGGCACPAATTT TCAAA1GGGATAATAAk 10 AOCCAkAGZ'AAAGOZ-TGCClGAAGOT-CT TGGGACCGCAGTAAA1-'AGATATT TT AOGAGC21AACAOGT GATAAkTAGGOT TGCATTAG TTACC TATGGTTCAGATATTTTTGATGGTAGOAGTOTAGATG TCOTAAAAGOATTTAAMAROAATGAkTAAATATTATGOCCTTCxAC~TAAGTTCAGAAlTTG-A GAkCAAGAA~TTATAGTGAiTAAACAAT TAACA-,AATAZATGC TGAAOAPGAT T ATAAAAAGGAT T' 15 AILAAGCAGTACTATCTT-AGTAA.AGTAGGGAAACATTTACTATGAAAGCCTTCATGAOG-C AGATGATATTTTGAGTCAAGTAGA, TCO'AAATAGTCrAAA-AATTAT TOGTTGATATAAC-7 TGAT 0010 TTGCAAGAAG,-ATCATATGCTATTAATA ATTTTAAATTGGOTGCATCATATG-AAAkGG'C AATTTGPCA.-A ATGIAAzAAAAkATGOATATOT!-AAAkTAAAAOATAATT TTCTAC TTAC ITOATAA CCCOAGGATATAAA-'AGO-AAAi. TGGGGAGT TACTTTTTGT TTGOCCCTTAGATAGT TATCA 20 ACACAGATAATC TCM TGAAAC T TACAAAAAC TT CAT TAT T TAGATTTAAATGCTTAAT TACO C TAAAOGTA.CAATT TAT"r,'iCGAAATGGAC-CAG' AAG(:AGAACATG.."GAA CACCPACCA.;ACTT 'TA TATAAATAOTTTAAA.AACAGPAAAATTATGACATCTTTAATTTTOGGTATAOATATATCTGCT TTTAOACAAGTT TATAATOAOOGATT ATAAOGPAAAATC"AAOGATOO GTAC T T TTC AAAAAT TOA AAGAOIGAkC TT TTOAA:CT TTCAGATGOG 'AATr--AAOAACTAZiATGAAO7kTCA"PTTC TOTTC 25 TArAACC EGGTATT' IATACCCCGATiA.GTIAAC TT. CAT]CC"GATC5C"ATCT("AACPATGAA;ATT 'P'TA TCTP-AAATTCAGCA.ACAA T TTGAAAAO-GTT TTAA'CAA,AOAAAAZ'CTC AATTG TA.ATOGAA F"TAAAACCAT' TGCAATCA 1TAAGC TGGCAA'GGA' AACATTGCA A-CAGTO3TATTATACTT TAC-AOGGAA14ATOATOGAAG TATA-ATOAAAGATAGG'-ATTOCAAC T G-GTG-GGCCTAATAATGATGGTO,'GAAT'ACTTAAkAOOOGTTAAATTAOAA TAC. TCAAA AATA, 3 0 AAC TCTACO TTAAGG GT T TACT TAOGGOAG GGACAAA2AAG TAAC AC TOAC ATAT GAT OT G'.AAAC.TAGATGAC.AGT PT TTATAAOTAACAAAT TC TAT GAC AC TAAT GOGTAOAACAACAT TOG AATC-CTAAATC-AGAOOATCC TAATACAC TTAGI-'GATT TTCCAA TCCCTAAAATc*TCGTiGATO!e T GAOGAGAAT AT CC T A CAA TAACG A TTAAAAAC GAG AAGAA GT TA GG TG7A:AT TOGAATT TlAGC AAAAGT TOATAAAOATAATAATAAO, 3TGCIT I'(CAAAOPGAGC TACGT'r']GA.AC TTCAAGAA2 35 TI TA-ATGAAkGAT-TATAAAC ICTTTATTT-APCA ATAA-AAkTAATAAT TCAA-AAGTAGTGAC GO OrAGAAA ACGGC-AAAA TTTCTTACA. .G%%AT TTGAAAGATGGCAAATATGAGT TAATAGAAC' A GIT TC-'-,G CCG AAG GA TTA T CAAAAAAT T AC T AT AAA CC AA T TT TAAC T TT TOGAAO-T IT TT AAAOGAI'CGATI.ACAAAA'IYAT'3ATAGCTiGT 'TAATrAAACk'-AGAT TT]"C .IGAATIAT'CAI AGGAAG" G T GACAA GC A TTT A AT T A CCAA C A CA TJAT T CCACCAIAG GAAiT T AT TC COGATuGACA G G 40 TGOAAA SEQ ID NO: 12 Construct 6: gbs2Ol8p 45 TT-AOTOTGAAGAzATTT-GATTTCT' AAA -TATCOTOOTAATGCCAAAGC"TATTCTATACTTIT AAOT IAOAGTAAAkTGAT T :'TATAGAOACATOAOAGGATAOAO -TTOOACAAT TAATTAATAGT AC TGAAGCAGAAAT TAO-AAAT AT TT TAT ATC.AAOOACt .AATT'IGO',tAAOCAAA,,,ATAAACCAA,,U GTGTAACTA-CACATCCTAAAGTTAOIGATCAAGAAOTAGCTAGCA GTCA-AGACGTTC.-TCA AGATATOCATTAAO GT CTTAGGT T TOOCT T TOAFT CAGAC CAA-AAAGAT.AT TT TAOTTAAATOI 50 AT'T GITCTTCNLGA ''GCACTT AT TOC T TAAA TTT G TAACITC AAOCA C GOAC 2TOGA ATAATGCTGAATCAA, AAOTAGCAAGGTAATGO4GGC AAAAA -51 TATAAGCCCCGAkGTCTTAGAAGAATATAAAGAAAAAAT TCAAAGAGC TAGACTAAGAGT CAAGTTGATGAGT TTGTAGCAGAAGC TAAAAAAGT TGT TAA T TCCAATAAAGAAACGT TGG TAAA TCAGGCCAA.TGGTAAAXACAAGAAA T TGCTAAGT TAGAAAAT T TA TC TAAC GATGA AATGTTGACATA T AAT ACTGCAAT TGATAATGT AGTCAAOACAGT ATAATGAAGGTAAGC TC 5 AATATTACTGCTGCAATGAATGCTTTAAATAGTATTAAGCAAGCAGCACAGGAAGTTGCCC AGAAAAAC TTACAAAAGCAGTATGCTAAAAAAATTGAAAGAATAAGTTCAAAAGGATTAGC GT TATCTAAAAAGGCTAAAGPAAT TTATGAAAACA T AAAAGTAT T TTGCCTACACCTGGA TATTATGCAGACTCTGTGGGAACTTATTTGAATAGGTTTAGAGA TAAACAAACTTTOCGGAA ATAGGAGTGTTTGGACTGGTCAAAGTGGACTTGATGAAGCAAAAAAAATGCTTGATGAAGT 10 CAAAAAGCTTTTAAAAGAACTTCAGACCTTACCAGAGGTACTAAAGAAGATAAAAAACCA GACGT TAAGsCOAGAAGCCAAACCAGGCCAAACCAAA TAT TCAAGTACCTAAAAAGCAC OTACAGAAGC TGCAAAACCAGCTTTGTCACCAGAAGCCTTGACAAGAT TGACTACATGGTA TAATCAAGC TAAAGATC TGCT TAAAGATGATCAAG TAAAGGACAAATACGTAGATATACT T CAG T TCAAAAAGC TGTTCCAAGCT TA TGAT CA GTGGAAGAGGGAAAA T T TAT TACCA ;5 OTGATCAAGCAAATCAATTAGCTAACAAGCTACGTGATGCTT TAOAAAGTTTAGAATTAAA AGATAAAAAAGT AGCCAAACCAGAAGCCAAAACCAGCCCCCAAOCAGAAGCTAAGCCAGAA GCT AAGCCAGAAGC TAAGCCAGAAGC T AAGCCAGAGGCCAAACCAGAAGCTAAGCCAGACG T TAAGCCAGGACTAAAAAAGAGCT TAAAOOCACCOTAAGCCAGAAGCTAACCAGAGGC T AAGTOCAGAAGCTAAACCAGAGGCT AAGC TAGA

A

GCTAAACCAGGCCAAACCAGCAACC 20 AAAAAATCGGT TAATACTAGCGGAAACTTGGCGGCTAAAAAAGCTAT TGAAAACAAAAAGT ATAGTAAAAAATTACCATCAACG Egpresion anpurjcation opLrns: E. coli BL21 star cells harboring the recombinant plasmid were grown into log phase in the required culture volume. Once an ODeoom of 0.6 was mached the culture was induced with 0.5 mM IPTG for 3 hours at 37*C. The cells were harvested by centrifugation, lysed by a combination of the freeze-thaw method followed by disruption of cells with 'Bug-buster*', (Novagon). The lysate was separated by centrifugation into soluble (supernatant) and insoluble (pellet) fractions. Depending on 30 the location of the protein different purification strategies were applied. A) If the His tagged protein was in the soluble fraction, protein purification was done by binding the supernatant to Ni-Sepharose beads (Ni-Sepharose tm 6 Fast Flow, GE Healthcare). Due to the presence of the hexa Histidine (6xHIS) at the C terminus of the expressed protein, it bound to the Ni-Sepharose while the other contaminating proteins were washed from the 35 column by wash buffer. The protein was eluted by 500 mM Imidazole in 20 mM NaH 2

PO

4 , 0.5 rmM NaCl buffer at pH 7.4. The eluate was concentrated, assayed by Bradford for protein concentration and checked by SDS-PAGE and Western blot. B) If the protein was present in the insoluble fraction, the pellet was solubilized in suitable buffer containing 8 M urea and applied onto the Ni-NTA column under denaturing conditions (in buffer 40 containing 8 M urea) using the same materials and procedure as mentioned above. Contaminating proteins were washed from the column by wash buffer without urea, - 52 Refolding of the iis-tagged protein was performed while the protein was immobilized on the Ni-NTA matrix. After renaturation, proteins were eluted by the addition of 500 mM Imidazole. The cluate was dialyzed to remove traces of urea and concentrated if the volume was large, checked by SDS-PAGE and measured by the Bradford method. 5 Animal protection studies Animals: CD-I female mice (6-8 weeks) were used for these studies. div' ianumizatia generation of hIner-imume mousesra: 50 pg of recombinant .0 protein was injected subcutaneously into CD-I mice, adjuvanted with Complete Freund's adjuvant (CFA). Animals were boosted twice with the same amount of protein and Incomplete Freund's adjuvant (IFA) at days 14 and 28. The published protective Sip (gbs0031) protein antigen (Brodeur et al, Infect Immun. 68(10):5610-5618 (2000)) was used as a positive control, while mice immunized with adjuvant only served as negative 15 controls. Antibody tires were measured at day 35 by ELISA using the respective recombinant proteins. In case of hyper-inimune sera generation mice were terminally bled at day 35. Gener aton or hperimmune ranit scrc;: Polyclonal rabbit sera were generated for 20 gos003 , gbs0233p, gbsI087p, gbsl309p, gbsi477p, gbs1478p and gbs2018p at Charles River Laboratories, Kislegg, Germany. 250 sg of recombinant protein was injected into New Zealand White rabbits, adjuvanted with Complete Freund's adjuvant (CFA). Animals were boosted three times with the same amount of protein, but with Incomplete Freund's adjuvant (IFA) at days 28, 42 and 56. Antibody titers were measured at day 38 and 52 by 25 ELISA using the respective recombinant proteins. Rabbits were terminally bled at day 70. Passive immunization: CD-1 mice were immunized intraperitoneally I to 3 hours before the bacterial challenge with 150 pl mouse or rabbit hyperimmune sera. 30 Bacterial challenge: Freshly grown S. agalactiae strains C388/90 (serotype la/c), A909 (serotype Ia/c), ATCCI2401 serotypee 1b), ATCCi2403 (serotype III), COHI serotypee III), BAA22 (serotype III), 2603V/R (serotype V), ATCC49447 serotypee V), BAA23 (serotype V) were used for animal challenge studies. In order to determine the viable cell numbers present in the bacterial inoculun, cfus were determined via plating on blood agar - 53 plates. 106 - 108 efus were applied intraperitoneally into mice. Protection by immunization was measured by a lethal sepsis model, where survival rates were followed for I to 2 weeks post-challenge and survival was expressed as percentage of the total number of animals (10 mice / group). 5 Results By using a genomic scale antigen identification method we selected Group B streptococcal antigens based on immunogenicity in humans (W02004/099242) and pre-selected vaccine 10 candidates based on in vitro assays. Here we show immune protection by six Group B streptococcal antigens in animal models. The first screening model was set up using adult mice and the mouse-adapted S. agalactiae ATCC12403 serotype Ill strain that was also used for the genomic library construction and cloning of some of the vaccine candidates. We set up the method with CD-I mice and defined the LD9 0 - LI 1 3wo dose. The model set 15 up was further optimized by using positive and negative control sera. Protection was estimated by reduced lethality of mice immunized with Sip or anti-Sip immune sera relative to animals immunized with adjuvant alone or treated with control sera. Based on these data, CD-I mice and a challenge dose between 5 x 107 to I x 108 cfu was used for further studies. Mice were immunized first with the recombinant antigens adjuvanted with 20 CFA/IFA and in subsequent experiments with hyper-immune mouse sera transferred to naive animals before challenge with S. agalactiae ATCC12403 serotypee 111). In the active, as well as in the passive model, several protective antigens were identified that showed variable protection levels, ranging from higher, equal or lower survival relative to Sip. Since several different Group B Streptococcus serotypes are able to cause severe disease in 25 humans, it is important to test cross-protection of vaccine candidates against all major serotypes in animal experiments. Moreover, it has been firmly demonstrated that protective antigens show strain-dependent variations not only in their primary sequences and expression, but also in their protective capacity. For that reason, we have set up the screening model with several different S agalactiae strains representing the major 30 serotypes, ]a, Ib, Ill and V. Strain-dependent protection within one serotype was also addressed by using 2-3 different strains of the most common serotypes la, III and V. In order to perform this large number of experiments with the minimal animal sacrifice and good comparability, we generated hyper-immune rabbit sera for all in vitro selected recombinant antigens. Three rabbits were immunized with each individual antigen - 54 adjuvanted with CFA/lFA using a standard protocol. Animals were pre-screened for pre existing GBS-specific antibodies by testing their sera with ELISA and only animals without a significant reaction were included in immunization studies. The individual hyper-immune sera were then analyzed for antigen-specific antibody levels and used in 5 pools for further analyses. Thus, the very same immune sera were used for passive protection studies with nine different GBS strains that we found useful for animal studies. As a result of these experiments we could identify six novel vaccine candidates gbs0233p, gbsI087p, gbs1309p, gbsl477p, gbsi478p and gbs2018p - that showed protection against at least one serotype when used as a sole antigen (Figure 1). 10 In order to examine benefits of combinations of different antigenic components, we performed passive protection studies by combining rabbit sera with different antigen specificities. With different combinations using these six protective vaccine candidates, we could demonstrate increased protection compared to the single proteins against all the 15 tested GBS serotypes. The combination of gbsl477p + gbs20l8p provided a significantly increased level of protection against many scrotypes. The best protection seen so far was achieved with a combination of gbsiO87p + gbsi477p + gbsl478p + gbs2018p that protected most of the mice against all nine tested GBS strains (Figure 2). 20 Example 2: Surface exposure and induction of functional antibodies by Group B streptococcal antigens. Experimental procedures 25 FA CS analysis: The S. agalactiae strain to be tested was inoculated from a glycerol stock into 5 ml THB medium and incubated over night at 37"C. The overnight culture was reinoculated by 30 adding 200 p l into 10 mi fresh THB medium and incubated until an ODooom of approximately I was reached (~5 x 10 cells/mli). The bacterial cells were pelleted by centrifugation at 4,000 rpm for 5 min and washed twice with 2 ml HBSS. The final pellet was resuspended in HBSS with 1% BSA to give a cell density of 5 x 106 celLs/ml. To 100 pi bacterial suspension 1 pl serum was added and incubated for 45 min on ice. Bacteria - 55 were pelleted by centrifugation at 1,000 g for 4 muin and washed once with 150 1 HBSS with 1% BSA and resuspended in 100 pl HBSS with 1% BSA. To the opsonised bacteria I pil of the secondary antibody (goat F(ab)2 fragment anti rabbit IgG coupled with PE) was added and incubated for 45 min on ice in the dark. The cells were washed twice with 150 5 pl HBSS as described above and dissolved in 250 pl HBSS, the cells were fixed by the addition of 250 pl 4% pare-formaldehyde. The fluorescent staining of the bacteria was measured by FACS analysis. Opsonophagocytic killing assay 10 Preparation of bacterial cells: The S. agalactiae strain to be tested was inoculated from a glycerol stock into 5 ml THB medium and incubated overnight at 37 0 C. The over night culture was reinoculated by adding 200 gi into 10 ml fresh THB medium and incubated until an OD 600 of approximately I was reached. The bacteria were pelleted by 15 centrifugation at 4,000 rpm for 5 min and washed twice with 2 ml HBSS. The final pellet was resuspended in HBSS with 0.125% BSA to give a final concentration of 5 x 104 cells/85 pi. Preaaration oftRA W264.7 cells: Cells were cultivated in T175 flasks with 25 ml DMEM 20 high glucose medium at 37 0 C with 5% CO 2 Cells were detached from the flasks by scraping and collected by low speed centrifugation at 1,000 rpm for 10 min and washed twice with 50 ml HBSS with 10 mM glucose and resuspended in HBSS with 10 mM glucose to give a cell concentration of I x 10 cells/miL 25 OpsonophageOVtic lliing assay: Bacteria (85 pl) were mixed with 10 p1 guinea pig complement and 5 pl prediluted serum and incubated for 60 min at 6"C with shaking (500 rpm). To the opsonised bacteria 100 pl (1 x 106 cells) RAW264.7 cells were added. Three aliquots of 10 pl were taken and each added to 1.5 ml water after 5 min incubation, 100 pl were plated on blood agar plates to determine the initial bacterial count, T. The 30 suspensions with opsonised bacteria and RAW264.7 cells were incubated for one hour at 37"C with shaking (500 rpm). After 60 min incubation three aliquots of 10 pl were removed and each diluted in 1.5 ml, after 5 min incubation, 100 pl were plated on blood agar plates to determine T 60 . After overnight cultivation cfus were determined with a colony counter.

-56 Evaluation: For each sample the relationship between the cfu at To and T 60 was determined. The percentage killing of each test scrum was related to the respective preimmune serum using the relationship between To and T 60 with the formula 100 5 10Ox(test scrun'preimmune scrum). Results The analyses of surface expression of gbs0233, gbslO87, gbsI309, gbs1477, gbsl47s and 10 gbs20l8 have been performed by FACS analysis using the very same pooled rabbit hyperimmune sera that were tested for protection in animal studies. These six protective antigens were detected on the surface of Group B streptococcal strains. Four of the antigens (gbslO87, gbsl477, gbsl478, gbs20l8) were most consistently detected (Figure 3), gbs0233 was not expressed in vitro by all strains and gbs1309 was mainly detected in 5 the bacterial supernatant. The in vitro expression experiments have been performed with nine different strains from the serotypes la, lb, II, I1, TV and V; the most comprehensive studies have been performed with the serotype Il strain ATCCI 2403. Based on the passive protection data, it is firmly established that protection by the selected 20 six vaccine candidates is mainly mediated by antibodies. The ability to measure functional antibodies in in vitro assays is essential for the development of both a prophylactic vaccine and an antibody-based therapy or prevention. Nine different S. agalactiae strains representing six serotypes (Ia, lb, i1, l,, IV and V) were used to evaluate gbs0233p, gbsiO87p, gbsi309p, gbsl477p, gbs1478p and gbs2018p for induction of functional 25 antibodies. Included in the opsonophagocytic killing assays were two GBS strains representing serotypes 11 and IV that were not suitable for animal testing. As an example of the in vitro assays, results with two strains are presented in Figure 4, the scrotype 11 strain AC3912 (Figure 4A) and the serotype V strain BAA23 (Figure 4B). Simultaneously with the opsonophagocytic killing assay cells were tested for in vitro expression of the tested 30 antigens by Western blot and FACS analysis. At a serum dilution of 1:200, only gbs1478p showed more than 50% killing of the serotype 11 strain AC3912 (Figure 4A), both gbsl477p and gbsl478p showed more than 50% killing of the serotype V strain BAA23 (Figure 4B). The remaining antigens showed less than 50% killing of the strains tested in - 57 Figure 4, which in most cases can be explained by poor in vitro expression of the antigens in these strains, 5 Example 3: Sequence conservation of protective Group B streptococcal antigens Experimental procedures Sequence analyses of'S agalactiae genes: In order to determine the sequence of an antigen :o from diverse S. agalacdiae strains, PCR was performed with primers specific for the gene of interest, S. agalactiae strains used for these analyses are shown in Tables 2 and 13. Oligonucleotide sequences as primers for PCR were designed for the selected antigens in order to be able to amplify the full gene. Sequencing was performed with dedicated primers using the PCR products as templates. The sequences of the oligonucleotides are 15 listed in Table 3. Genomic DNA of all S. agalactiae strains was prepared as described in W02004/099242. PCR was performed in a reaction volume of 25 pl using Taq polymerase (1 U), 200 nM dNTPs, 10 pMol of each oligonucleotide and the kit according to the manufacturer's instructions (Invitrogen., The Netherlands). As standard, 30 cycles (lx: 5 min. 95 0 C, 30x: 30 sec. 95 0 C, 30 sec. 56C, 30 sec. 72C, lx: 4 min. 724C) were 20 performed, unless conditions had to be adapted for individual primer pairs. PCR samples were sequenced with the oligonucleotides as listed in Table 3. Results 25 The genomic sequence of eight individual strains of S. agalactiae (Tables 2 and 4) has been published and was compared for the six antigens shown to be protective under Example 1. Thc comparison showed that the proteins gbs0233 and gbs1087 are highly conserved (more than 99 and 91% identity, respectively; Tables 2 and 4), although gbsi087 displayed various numbers of repeats in the different GBS strains (see also 30 W02004/035618). This high degree of protein sequence identity (gbs0233: >99%; gbsiO87: >86%) could also be observed for the strains that were subjected to DNA sequence analyses as listed in Tables 5, 7, 8, and Table 13 and in the Sequence listing. The gbs0233 protein from any of the analyzed strains showed at least 98.7% amino acid sequence identity to gbs0233 from S. agalactiae NEM316, with only 6 amino acid position - 58 showing a change. The sequences of the gbsl087 proteins from the analyzed strains were also highly conserved, yet the different strains harboured between a single and up to 29 repeats of a highly conserved 17 amino acid long sequence. The sequences of proteins gbsl309 and gbs2018 showed high sequence conservation in 7 genomic strains (more than 5 87 and 77% identity, respectively), while protein sequences diverged more significantly in strain COHI (69.9 and 47.7%, respectively; Table 4). The gbs1309 protein showed a similar high degree of amino acid sequence identity (89.6%) in the sequenced GBS strains (Table 5, 9, 13 and Sequence listing), while the gbs2018 protein can be classified in two clades, with 95% of strains belonging to one clade with at least 60.8% sequence identity 10 and 3 strains COHI(ll), BAA22(II) and 49447(V) belonging to the second clade. The protein gbs1478 is highly conserved in 6 genomic strains (more than 87% identity), yet the strains COHI and A909 show a lower amino acid sequence identity of approximately 43% (Table 4). Protein gbs1478 is conserved in most analyzed GBS strains as shown in Table 5, 11, 13 and the Sequence listing, but exists as 2 distinct clades with an amino acid sequence 15 identity of more than 80% in the dominant clade (approx. 80% of analyzed strains) and more than 99% in the second clade. The protein gbs1477 shows the highest degree of amino acid sequence variability, with six distinct clades that can be characterized. Strains COHI and A909 do not encode a homologous protein with significant amino acid sequence identity (Table 4). The sequence analyses of the gbs1477 gene from further 20 distinct GBS strains revealed that all selected strains encode a protein homologous to gbs1477 and that all six clades were covered by these sequences (Table 5, 6, 10, 13, Sequence listing and Figure 5). The prototype sequences for the 6 clades of gbs1477 are: strain 12401 (clade 1; SEQ ID NO: 93), strain 1C254 (clade 2; SEQ ID NO: 110), strain 126H4A (clade 3; SEQ ID NO: 94), strain 49447 (clade 4; SEQ ID NO: 95), strain 25 C388/90 (clade 5; SEQ ID NO: 100) and strain NEM316 (clade 6; SEQ ID NO: 223 and SEQ ID NO: 361); (for all sequences, see Sequence listing). Within any single clade the level of amino acid sequence identity reaches at least 98%. Example 4: Group B streptococcal antigens and combinations thereof as well as 30 mouse monoclonal antibodies, generated against these antigens, induce protective immune responses against lethal sepsis in an i.p. challenge model. Experimental procedures -59 Cloning and expression of recombinant Group B streptococcal proteins Cloning ofgenes: The gene of interest was amplified from genomic DNA of S. agalactiae ATCC12403 serotypee 111) by PCR using gene specific primers. Apart from the gene 5 specific part, the primers had restriction sites that aided in a directional cloning of the amplified PCR. product. The gene annealing (specific) part of the primer ranged between 15-30 bases in length. The PCR products obtained were digested with the appropriate restriction enzymes and cloned into the pET28b (+) vector (Novagen) for His-tagged proteins. Once the recombinant plasmid was confirmed to contain the gene of interest, E. :o coli BL21 star* cells (Invitrogen) that served as expression host were transformed. Cloning of the gbs1087, gbsl477 and gbsl478 genes has been performed using genomic DNA from strain S. agalactiae 6313 (scrotype 111) in the vector pET28a (-). The constructs of the selected antigens are listed in Table 1. t5 Ernression and purification ofproteins; E coli BL21 star* cells harboring the recombinant plasmid were grown into log phase in the required culture volume. Once an ODcooarm of 0.6 was reached the culture was induced with 0.5 mM IPTG for 3 hours at 374C. The cells were harvested by centrifugation, lysed by a combination of the freeze-thaw method followed by disruption of cells with 'Bug 20 buster*' (Novagen). The lysate was separated by centrifugation into soluble (supernatant) and insoluble (pellet) fractions. Depending on the location of the protein different purification strategies were applied. A) If the His-tagged protein was in the soluble fraction, protein purification was done by binding the supernatant to Ni-Sepharose beads (Ni-Sepharose' 6 Fast Flow, GE Healthcare). Due to the presence of the hexa Histidine 25 (6xHIS) at the C terminus of the expressed protein, it bound to the Ni-Sepharose while the other contaminating proteins were washed from the column by wash buffer. The protein was cluted by 500 mM Imidazole in 20 mM NaH 2

PO

4 , 0.5 mM NaCl buffer at pH 7.4, The cluate was concentrated, assayed by Bradford for protein concentration and checked by SDS-PAGE and Western blot. B) If the protein was present in the insoluble fraction, the 30 pellet was solubilized in suitable buffer containing 8 M Urea and applied onto the Ni-NTA column under denaturing conditions (in buffer containing 8 M Urea) using the same materials and procedure as mentioned above. Contaminating proteins were washed from the column by wash buffer without urea. Refolding of the His-tagged protein was performed while the protein was immobilized on the Ni-NTA matrix. After renaturation, - 60 proteins were eluted by the addition of 500 mM Imidazole. The eluate was dialyzed to remove traces of urea and concentrated if the volume was large, checked by SDS-PAGE and measured by the Bradford method. 5 Animal protection studies Animal CD-I female mice (6-8 weeks) were used for these studies. Active immunization: 25 pg of recombinant protein was injected subcutaneously into CD I mice, adjuvanted with ALUM 1%. Animals were boosted twice with the same amount of protein and ALUM 1% at days 14 and 28. The published protective Sip (gbsO031) protein 10 antigen was used as a positive control, while mice immunized with adjuvant only served as negative controls. Antibody titres were measured at day 35 by ELISA using the respective recombinant proteins. Generation of hvperimmune rhhitj era: Polyclonal rabbit sera were generated for 15 gbs0031, gbs0233p, gbslO87p, gbsl309p, gbsl477p, gbsl478p and gbs2018p at Charles River Laboratories, Kislegg, Germany. 250 pg of recombinant protein was injected into New Zealand White rabbits, adjuvanted with Complete Freund adjuvant (CFA). Animals were boosted three times with the same amount of protein, but with Incomplete Freund adjuvant (IFA) at days 28, 42 and 56. Antibody titers were measured at day 38 and 52 by 20 ELISA using the respective recombinant proteins. Rabbits were terminally bled at day 70. Generation of mouse monoclonal antibodies: Monoclonal mouse antibodies were generated against gbs0233p, gbsl087p, gbsl477p, gbs1478p and gbs2018p at Abgent, San Diego, USA. 100 p g of recombinant protein was injected into Balb/c mice, adjuvanted 25 with Complete Freund adjuvant (CFA). Animals were boosted with 50 pg protein and CFA at week 2; at week 3 animals were boosted with the same amount of protein, but with Incomplete Freund adjuvant (IFA) and at week 4 and 5 animals were boosted with 50 sLg protein in PBS (without adjuvant). Antibody titers were measured in week 5 by ELISA and Western blotting using the respective recombinant proteins. Spleen cells from mouse with 30 the best titer were fused with myeloma cell FO using PEG protocol. Subsequently growing fused hybridoma clones were screened against the respective antigen for test of their specificity and sensitivity. ELISA positive clones were tested also by Western blot. Selected clones from this test were subeloned at least two times and antibodies were purified by protein G affinity chromatography from culture medium.

-61 Passive immunization (neonates): Pregnant CD-I mice were given 0.5 ml undiluted rabbit hyper-immune sera by intraperitoncal injection 2 to 4 days before delivery. Within 48h after birth, pups were challenged intraperitoncally. Bacterial challenge: Freshly grown S. agalactiae strains C388/90 serotypee la/c), A909 (serotype Ia/c), ATCCI2401 (serotype Ib), ATCC12403 (serotype III), COHI serotypee Ill), ATCCBAA22 (serotype 1I), 2603V/R serotypee V), ATCC49447 serotypee V), ATCCBAA23 (serotype V) were used for animal challenge studies. In order to determine 10 the viable cell numbers present in the bacterial inoculum, efus were determined via plating on blood agar plates, 106 - 108 cfus were applied intraperitoneally into mice. Protection by immunization was measured by a lethal sepsis model, where survival rates were followed for I to 2 weeks post-challenge and survival was expressed as percentage of the total number of animals (10 mice / group for active immunization; for neonatal challenge 5 number of animals depends on the litter size). Results By using a genomic scale antigen identification method we selected Group B antigens 20 based on immunogenicity in humans (WO04/099242) and pre-selected vaccine candidates based on in vitro assays. We have shown previously immune protection by six Group B streptococcal antigens in animal models. Additionally, with different combinations using these six protective vaccine candidates, we demonstrated increased protection compared to the single proteins against all the tested GBS serotypes. The combination of gbsi477p + 25 gbs20J 8 p provided a significantly increased level of protection against many serotypes. The best protection seen so far was achieved with a combination of gbs1087p + gbs1477p + gbsI478p + gbs2Oip that protected most of the mice against all nine tested GBS strains (see Example I and Figure 2). So far these experiments were obtained in serum transfer experiments. We now further substantiated these results by active immunization of mice 30 with two, three or four recombinant proteins using ALUM as adjuvant (Figure 6). Immunization with single proteins verified the data already obtained with the hyper immune rabbit sera (Figure 7). Since GBS sepsis affects mainly newborns, we have also developed a model that can demonstrate protection in neonatal mice. We established a urine model with passive - 62 immunization of pregnant mice with hyperimmune rabbit sera (500 gl i.p.) 2-4 days before delivery and challenging their babies with S. agalactiae 24-48h after birth. We observed excellent protection of newborn mice born to mothers immunized with the combination of gbslO87p + gbsl477p + gbsi478p + gbs20I8p specific immune sera (4 x 125 pl) (Figure 5 8). Hyperimmune sera against the individuals antigens were also effective in this, but overall was lower than that obtained with the combination of four (data not shown). These findings are very significant, since the models with the different GBS strains were very stringent, resulting in death of infected pups within 24 hours. Since the protein gbs 1477 has the highest sequence variability and exists in different clades io (Table 5 & 6, Figure 5) the protection was analyzed using the adult sepsis/lethality model. Mice were immunized with fragments (corresponding to gbsl477p of strain 6313) of six different gbs1477 proteins, originated from distinct clades. Protection was measured against the homologous as well as against the heterologous clade (Figure 9). The best protection was always obtained when immunization and challenge is done with the 15 homologous clade. The more variable the sequences of the different clades are the lower the protection obtained in the sepsis model. This invention includes also protection data by mouse monoclonal antibodies. mAbs were generated against gbs0233p, gbs1O87p, gbsl477p, gbsl478p and gbs2018p. Selection of hybridoma supernatants were performed using antigen-specific ELISA and/or FACS 20 analysis. Per antigen two mAbs were selected and tested in the passive transfer model using 50 gg purified mAb. We demonstrate in this invention that we obtain protection with a single mAb against at least one serotype (Figure 10). In order to examine benefits of combinations of different mAb components, we performed passive protection studies by combining mAbs with different antigen specificities. We could demonstrate increased 25 protection compared to the single mAbs against all the tested GBS serotypes. The best protection seen so far was achieved with a combination of mAbs against gbsO233p + gbslO87p + gbsl477p + gbsl478p + gbs2018p that protected most of the mice against all nine tested GBS strains (Figure 11). 30 Example 5: Group B streptococcal antigens and mouse monoclonal antibodies, generated against these antigens, induce functional antibodies against group B streptococcus.

- 63 Experimental procedures FA CS analysis The Streptococcus agalactiae strain to be tested was inoculated from a glycerol stock into 5 5 ml THY medium and incubated over night at 370C. The overnight culture was re inoculated by adding 200 I into 10 mt fresh THY medium and incubated until an OD 6 oim of approximately I was reach (~5 x 100 cells/mi). The bacteria were pelleted by centrifugation at 4,000 rpm for 5 min and washed twice with 2 ml HBSS. The final pellet was resuspended in HBSS with 1% BSA to give a cell density of 5 x 106 cells/mt. To 100 A0 pl bacteria, I jd immune serun was added and incubated for 45 min on ice. Bacteria were pelleted by centrifugation at 1,000 g for 4 min and washed once with 150 pl HBSS with 1% BSA and resuspended in 100 pt HBSS with 1% BSA. To the opsonised bacteria, I p1 of the secondary antibody (goat F(ab)2 fragment anti rabbit IgG coupled with PE) was added and incubated for 45 min on ice in dark. The cells were washed twice with 150 P1 15 HBSS as described above and dissolved in 250 pl HBSS, the cells were fixed by addition of 250 p1 4% para-formaldehyde. The fluorescent staining of the bacteria was measured by flow cytometry. Opsonophagocytic killing assay 20 Preparation of bacterial cells: The Streptococcus agalactiae strain to be tested was inoculated from a glycerol stock into 5 ml THY medium and incubated overnight at 37C. The over night culture was re-inoculated by adding 200 pl into 10 ml fresh THY medium and incubated until an ODoo.m of approximately I was reached. The bacteria were pelleted by centrifugation at 4,000 rpm for 5 min and washed twice with 2 ml HBSS. The final 25 pellet was re-suspended in HBSS with 0.125% BSA to give a final concentration of 5 x 104 cells/85 A. Preparation of RAW264.7 cells: Cells were cultivated in T175 flasks with 25 ml DMEM high glucose medium at 37'C with 5% C2. Cells were detached from the plates by scraping and collected by low speed centrifugation at 1,000 rpm for 10 min and washed 30 twice with 50 ml HBSS with 10 mM glucose and re-suspended in HBSS with 10 mM glucose to give a cell concentration of I x 10' cells/mi ii Bacterial cells (85 st) were mixed with 10 s1 guinea pig complement and 5 p1 pre-diluted serum and incubated for 60 min at 64C with -64 shaking (500 rpm). To the opsonised bacteria, 100 pl (1 x 10' cells) of RAW264.7 cells were added. Three aliquots of 10 p1 were taken out and added to 1.5 ml water after 5 min incubation, 100 pl were plated out on blood agar plates. This CFU determination served as the initial bacterial count, To. The suspension of opsonised bacteria and RAW264.7 cells 5 was further incubated at 37 0 C with shaking (500 rpm) for 60 min and then the T60 was determined as described for the T(. Blood agar plates were incubated overnight and the CFUs determined on the next day using a colony counter. Evaluation: For each serum, the relationship between the CEUs at T and T60 was determined for the pre-immune and the immune serum, The percentage of killing of each 10 immune serum was determined by the following formula: 100-100x(immune serun/preimnune serum). A reaction without sera was included in each assay as negative (complement) control. Results 15 Based on the passive protection data, it is firmly established that protection by tie selected six vaccine candidates is mainly mediated by antibodies. The ability to measure functional antibodies in in vitro assays is essential for the development of both a prophylactic vaccine and an antibody-based therapy or prevention. The same opsonophagocytic killing assay 20 that was developed for the in vitro validation and used for selection of vaccine candidates was employed to analyze the hyperimmune rabbit sera for the presence of functional antibodies. Seven mouse monoclonal antibodies and four rabbit sera representing four antigens were tested in the opsonophagocytic killing assay for functional antibodies and staining in flow cytometry of the serotype 111 GBS strain ATCCI2403 (Figure 12 and 13). 25 All monoclonal antibodies bound to the serotype Ill GBS strain ATCCI2403 as measured by flow cytometry (Figure 12). The opsonophagocytic killing assay with the rabbit and mouse monoclonal antibodies are shown in Figure 13. At a 1:1,000 dilution of the rabbit sera only gbsl477#28 and gbs1478#4 showed a high killing activity and gbsIO87#12 showed low killing activity. The mouse monoclonal antibodies generated against gbs1477p 30 and gbsl478p showed high killing activity and those against gbslO87p and gbs2018p showed only a killing activity at the higher concentration.

- 65 Table 1: List of genes selected for expression. The nomenclature of the proteins is derived from the genome of NEM316 (ATCCI2403). The strain and position (start/stop) of the amplicon within the full length genc/protein ar' indicated. .5 PutKsfak oEQ 4j SEQt bs0233 308 12403 pET28b 37-921 7 13-307~b 07 42 61 . E2 0-02 8 j3-5 2 3 ~ b1309 j403 12403 pET28b 4-1203 9 (2-401 3 ~4 bs477J| 674 6313 pET28a 88-1944 10 |130-648 4 6 ___gbs2018 643 H2403f}pET28tbH16-836 J 12 I36-612 6 Table 2: List of S. agalactiae strains which were used for the first run of sequencing of the most of the genes of interest, and for which the genome has teen published. (A complete 10 list of strains used for the first and second run can be found in Table 13.) GBS strains used for sequencing S. agalactiae strain Serotype 1C458 Ta 01 76H-4A I ATCCl12401 Tb BAA23 V COHI ITTII___________________ ATCCI2403 III 6313 III ________ Published genome de CBS strains (Malone et al, 2005~ Science 309(5731: 148-50) S. agalacliae strain Serotype COHI ___ III CJB1II1 A909 Ia/c ____________________ 515 Ia _________________ 2603 V/RV NEM3I6 (ATCC12403) III 18RS521 11 _______________ - 66 Table 3: Oligonucleotides used for PCR and sequencing ,protein P& Squndng Primer' Name ID, gb03 CC5455 & GGGGGCACAATTCCTGTTAT ICC 5455 13 gs231CC5456 AAAAGTGTGGATAAAnTGTTOT - ICC55 CATTGTAAATCTTAATGTTAGTATGA ICC 5489 1 TGACTTFTGATTTCCAACACTATCC ICC5490 16 gblI7~CC5489 & OGTTTTAGAACTTGAAATCAGGA } CC 5491 17 gbs187 IC549 ICATTANECATACN 5T92 18 AGAGAAAATAATCACTCTAGTCAAGG ICC 5493 19

F

5 4 9 4 AAAAAGTCACCCFAACCAACCd ICC 5494 2 AATCATCGGTGAAGTGACGA ICC 5465 21 1CC5465 & CGGfTAATCAATTGGATATTTTCT { CC 5466 22 ICC5468 ACTCTGATATCCCTAAAGGCTAr ICC 5467 23 gbsl309 1CC5469 & CCAGTAGATGAGTGGTTAGGTCTTG iCC 5469 25 1CC5470 XA"hG'ACC"C""FFATAT" TT (' 540 2 TT.CAG.TGGAAT TATAT GG CC 5471 27 1CC5471& TTC rTTTACTTGrGGTfOTCA ICC 54772 ICC5479 TCTTGGCTGATTCAAAXGCA iCC 547 29 GGTTCTGATGGGTTGATTGG BiCC 5479 30 ICC5480 & AATGGCTCTTGCTITATGATCT ICC 5472 31 1CC5472 TGTTAGCGGCTACACTCCAC iCC 5480 32 gbs 1477 TTOCXGOYOOAAYI'TAAiYG ICC 5471 3 1CC5471 & CAACTTTGWTCAGTTGG ICC 5475 34 ICC5475 CCCNTTGTCAAACCATT TiCC 5473 35 GCTACidCTdAAATCGGTMA ICC 5474 36 1CC5476 & CAACTCTCTCAGAACGT ICC 5476 37 1CC5472 'jT'i'Gg' nAiG' AT'C'T'f- -- C547-3 gs48ICC5481 &ITCTAGGATATTCTGTATCTCATcITTAC ICC 5481 39 CC44CCATCAAAAATATCTGAACCA TICC 5482 40 tdaGGGAACATTATCT AA ACGTATTTCA ICC 5483 4j -67 TTCAATFTTTGAAAAGTACCATCTTG ICC 5484 42 GAACATGGAACACCAACCAA ICC 5485 43 ICC5485 & TCAATTTCACCTAACTTCTTCTCG ICC 5486 44 ICC5488 TTTCCAATCCCTAAAATTCG ICC 5487 45 TTTTCATTTCTATCTCCTTCTTATTC ICC 5488 46 AAAAGGCAAAGTTCTGATGAGG ICC 5457 47 ICC5457 & AAAAATGCTTGATGAAGTCAAAA ICC 5458 48 ICC5460 GTTTGGCTTCTGGCTTAACG ICC 5459 49 TGATCAAGAACTAGGTAAGCACT( A ICC 5460 50 gbs20 18 ICC5461 & CAAATTTAAGAATAAGTTGCGAATC ICC 5461 51 ICC5462 AGAGTAAATGATTTAATAGAGCATCA ICC 5462 52 ICC5463 & AAATATTTTCTAAI'TCTGCTTCAGT ICC 5463 53 ICC5464 AATTAAAATAAACGTGGTCCTATCC ICC 5464 54 --- -- -- - - - ------ (A C 00n V.O NV -~.... .. ....... C C C 0 -I tillN! 0 e it v- Efl rfl C ------- - --- CIC C)'2 000 Co) 4?0t - 69 Table 5: Sequence identity of proteins as determined by the first run of sequencing. % Id, amino acid sequence identity of the respective protein in percentage as determined by DNA sequencing. All comparisons are performed to the respective protein of GBS strain NEM316. 5 .... %.. Id %... ... B% M d gs023. 99.0 100 990 99.0 9.7 99.7 gbslO87 86.0 95 2 93.9 91t5 92,7 98.6 Wihsi ~ 00 ±00 09 100 99 99.5 gbs1477 48.9 49 48.8 98.4 Nt67.8 determined gbsl478 88. 2 88 1 87.7 99.1 Not Nt determm.ed deermmned gbs2O18 77.6 99 7 77,2 78,5 INot0. determined Table 6: Sequence identity of gbs1477 proteins as determined by the first run of sequencing. % Id, arnino acid sequence identity of the respective protein in per-centage as 10 determined by DNA sequencing. Pairwise comparisons are performed for the gbs1477 protein among the sequenced GBS strains. & agal Ite{ ag.Albalae agtlaed & gtdy&glr 1 C$... ...... _ _ . .. .... .. .. . . ..... Sagalactnae NEM3I6 48 9 49.3 48.8 98.4 67.8 St agalacdiac IC105 0 58.6 99.9 49 4 48.0 a aaacriac 1C458 100 58,6 4935 53.2 Sagalacdae 12401 10494 47 9 S. agaiacdae BAA23 100 68.5 __ a.......H4 1 .... S. ~~~~ ~7 agi en I16I4 0 Table 7: Amino acid and encoding DNA sequences of gbs0233 proteins derived from different strains of S, agatactiae Strain 0176H4A OP.? DNA sequence (SEQ !D NO: 61) 5 ATGCTTAAT AAACaCACTTTTTAC-AGATATT TACACTTTCTTAGCCCTCTTAACGATTTCTGGTTGTCAAi TTA'ACCSATACT'A.?iA. aACCTGGTCATACCACP kTTAGTTCTCACAAC-kTTCTACAGAGTCTAGTATC ATCGCAA., ATTGTCACOG.AATTAATTCAkTCACGAATTAGG(-ATACAAC-ACAACTT TAATAAGCAATCTTGG-T TCCTC-TACGGTTACTCACCAAGCTTTGCTCCGTGCTGATGCTGACnTTGCTGCCACACGTTATA-AOSAACA G;ACATCACAG3GAACWCTTGGCTTAAC~CTGTTA, AGAC-CTAAGAAGCTTCTAGATTGTAAA ACTC AA 10 TTCCAY@AA CGCTACAATC.AAA? CTTGGTATCCTACITATGGTTg TTCTGATACTTATGCnTTC-ATGGTTAC'T AAkAGAGTTTGCCAGYACAGA-tTAAAATCACCAACATCTCTGATC m CA-AA-AAATTATCAACAACTATGAAGGC A GCGGTTGATAGTTCATGGATGAAITrCGAGGCACATGCATACACTCAITTTCGCTA4AAACATAC-GG?TTTOAA TTTTC'-ACATATTTACCCTATGCAPAATTCGCTTA GTOTATGATOCGOTTA.ATACAAAPATOCA.ATCTOTA TTAGGCTACTCCACTGACGGTCGTATTTCGAkGC TATGATTTAGAAATTTTAAOCCATGATAPAATTCTTT is C'CTCC TTATCAAG CCTCTATGGTTGVTCAACAATTCTATCATCAAA.-AGATCCTA2A.CTAAAAAATTACTC CATCGACTCGATQGT7-ATCATTTAIXAAtCP TG CAAAACCTTA.ATTA'TATGGTAGATGATA;LACTTTTA CAzACCTTCACTTOTTCCCAA3.ACAA.TTTTTAOAMP AAACCATTATTTTAGAGGAGATIA. ATAAt OP.? amin~o acid sequence (SEQ 20110: 55): 20 SSTVTHQALLRCDADIAATRYTGTDI TGTLGLKAVKOW(FA.SKI VE.,TEFQ~KRYNQTW Y PTYO;FSDTYAFNVT KEFA RQNKITK1 SDLE±KLSTTNEAOVDVESSWMNt-REGDGYTDFAKTYGFEFS]I'YPMQIGLVYD,'AV/ESNKMIQSV I;GYSTDGRI SSYDLE I RDDKKFFPY.AS1VVTt7,IS IIKKDPELKKLLNRLDGKINLKTMQNLNYt4Vf DDKLL EPSVVJAKQFLEKNHYFRGDK 25 Strain 12401 O_?_DNA ..sequence (SEQ I NO:-- 62): ATO-CTTAPAAAA.;TCQCACTTTTTArAATAT1'T. ' CCTTGCTTAGL CC'C.TTACGATTTCTGG TTGT CAA TTAACCf-GATAC-TAAAAA'u.PGTCTGGTCATACCACAtAT-AAtGOTTGCTCCCCAAOTTCTACAATT,T-'ATT ATCGCA5VJ TAT 'TATCACO2A~' :ATlh'tTTCAiTCAC-GAATTAGAiTACAACACAACTT TAATAAGCAATCTTGGT 30 TCCTCTACCSTTAC TCACCA AGCTTTGCTCCCTGGTGnTCTGACATTCTCCACOCTTAACAGGAAOAA G ACATCACA' GG CCTCTTCGT TTAluAAGCTGTTAkAAGACCCTAA%',AGAAGCTTCTAAGATTGTA.i AACTC AA TTCCA.AAAkACGCTACA.ATOAA ACTTOGTATCCTkCTTATGGTTTTTCTOATACTTATOCATTCATOCTTAC-T A.A AGAGTTTGCCACACAgAATAAAUATCACTAGATC-TC'TGATC TAAATTATCAACAJXCTArTGAAGC.A GGSGTTSATAGT CCATGGATGA.ATCCCOGAGGOP ATAS' ACACTGATTTCCCTMA-%ACATAC-GGT TTGAA% 35 TTTTCACA!TATTTAzCCOTATGO-AAATTGC TTATCTATGATGCGGTT AAGTACAA,-ATGCAATCTGTA TTAGGCTA'CT CACTCACGGTO GTATTTCGAGrCTATGATTTAGAAATTTT-AAGCOATGATAAAAAATTCTTT 'CTCO-TTATOA-AGCCTCTATG& TGTCAA C-A-TTCTATCATCAAAA-AAGATCCTA'AACTAAAAAAATTAC-TC C-ATCGA CTCGATGGTAAA;%ATCAATTTAAAA%.ACOATGCAAAACCTTALATTATATGTAAT3ATAACTT TTA SAkACC TTCAGTTG TTOCCA, ACA TTTTTAGAl-AAAACC ATTATTTTAGGGAGATAAF ATAA 40 arc amino acid seque nce (SEQ ID NO: 56): MLF2KSIFLQITLCLALT I SOCQLTDTKKSCI{TflKVAAQSST ESS MtAN! I TELT HP.ELGYNTTL I SNLG SSTVTHQALLRPC--DAPFIATRYTGTD;I TCTIJGLI{AVKD)PKEASKI VKTEFQKYNYQTWY PTYGFSDTYAFMT KEARQN I TKl SDLKKLSTTNRAGVDSSWMNP.REODOTDAPKTYGFESHIYPNQIGLVYDVESNKMQSV LGYSTDGRI SSYDLE I LRDDEKFPPYEAISM' INNS IT KKDPKLKRLLHRL.DGKINLRTNQNLNY hVDDKLL 45 EPFSVTA KQLE'EF FN HY FRGD 0 ___________________________ Strain BAA23 O DNA se nence (SEQ ID NO: 63) A' TGCTT .AAAAAi"TCGCACTTTTTACAGATATTTACACTTTSC"TTAGC -CTCTTAACGnTTTCTGGTTGTCAA 510 TTAAICCATACTAAAA -zAGTCTCGGTC-ATACCACAATWAA, GGTTCYY'rCCAAAGTTCTAAGAG;TCTAGTATT ATCGCAAA TATTATCACCG.AATTAATTCATCACOAATTAGGATACAACACAkACTTTA'ATAAGCAATCTTGGT TCCTCTACGGTTACTCAOCeAACCTTTGCT-CCTGGTGATVCTYXCATTGCTGCC-ACA CGTTATA ICACOAACA GACATCACAGGGACCTTGGTTTh-AAOCTCTTAG.,ACCCTA.AGAACTTCTAAGA;;TTGTA-,AACTGAAI TTCCAAAAiACG-CTACAATC AAAC~lTTGGTATCCTACTTATOGTTTTTCTGnTACWTTCT CATTCAkTGO7TTACT 55 A.AArAGTTTGC-CAGACAGAA-TAAAATCACTAAGATCTCTTATCTTA-A.IAATTATCA-CAACTATGAAGGCA GCGGTTGATAG TTCA TGCA-TGAATO GCGCGGATGOATACACT(JATTTCGCT~vAAAACATACGGTTTTOAA, TTTTCACATATTTA';CCCTATGCAsAATTGGCTTAGTCTATGTGCGGTTGAAACTAZACAAAAPTGCAATCTGTA TTAG JCTACTrCCACTGACGGTCGTATTTC(GA'GCTATCATTTAGAA r6PATTTTAR1gGGATGATAAA,7IAATTCTTT

CCTCCTTATGA-ACCCTOTATGGTTGTCAACAA,,TTCTATCATCAPAAAAGATCCTAAAOTAIAAAATTACTC

OATCGAOCTCGATGGTAAAA'PT4A TTTAAAAACGATGCAAAAOCT TAAT TATATGGTAGATGATPAACT TTTA G3AAOCTTCA'GTTGTTGCCACAATTTTTPc,CAA AAACCATTAT4TTTA AGOAtGATzAAATAA OR? ami-no ac27id stluence ($50 ID NO; 57; MLKESIFLQIFTLCLALLTIS8GCQLTDTKKSGNTTIW'VAAQSSTESSIMANII1TEL-IHEELGYNTTLITSNL 5 SSTVTHQALLRGDADIAAtTRYTOTD1TQTLOLKAVRYDPREASKIVRTEQKRYNQT y PTYGFSDTYAFM- VT LKEFARQNKITKI SDLRKLST TMKAGVDSSWNNPEG, DGYTDAKTYGF.EFSHI YPMQ 1GLVYDAVESNQAQSV LGYSTDGR1 SSYDLETILRDDI(KFFFPYEASMVVNeNS' I KDPKELLHRLDGXINLXTNQNLNYl{V7DDELL E P SWAKQE LE FNHRY FRG DI ____________ 10 Strain COHI OR DA - -_erie SQ ID NO.,64): ATGOTTAAAAAiJ% ATCGGACTTTTTACAGPJATTTAOAt'CTTTGOTTAGCCCTCTTAACGATTTCTGGT-TGTCPAA TTAA'-'CCGATAOTAA.AAAA-CCTGOTCATACCACAgATTA.AGGTTGCITGCCCAAGTTCTA-CAGAGTCTAGTATC ATGGOAJA ATATTGTCACOGrAATTAATTCATCACG AATTAGGATACAACACAACTTTAA;TAAGiCAATC'TO-GT 15 TCOTCT.ACGGTTAOTOACCSAOO, ,GTTTGCTOOOTGGTGATGOTGACATTGOTGCCACAOGTTATACAGGAACA G ACATCACAGGAAOCTCTTGGCTTAAPAAGOTGTTAAAGA.Cz -CCTAA IAGAAG;CT-TCTAAGrATT-GTA-AAAA3CTGrAAI% TTCCAAA.ACGCTACAATCAtXACTTGGTATCC7AOTTATGGTTTTTCTGZ'TACTTAT'GCATTCATGGTTACT AAGh AGTTTSCO-ACACAGoAA -TATC JA',CAAG%-~ATCTCTATTCAAAAGiTTATCA7OAAOLT'TAAvGG CA^ GGGGTTOATAGTTCATGGVATGIATCGCGAGGGAGATGGATAOAOT GATTTCGCTA&AACATACGGTTTTGAA 20 TTTTCACATATTTACCCTATGCAAAT TGGCTTATCTATGATGOGTTGTAAGTAA CtcAAATGC'AATCTGTA TTA-GOTACTCOAC-TGACGGTOGTATTTOGAOOTATOATTTAG14AAkTTTAAGGOATGrATM) lAAATTCTTT CCTOQTTATG AGCCT -CTATGGTTGTC-AAIC AtTTC'TATCATCAAAA-ALATACCTAAOTAAAAA- 'AATTAO-TO OATOGACTCGATOCTAMk'iATOAA.TTTAi 'AAAACGATGGAAAAiCCTTAATTATATGGTAQATGATAAC"TTTTA GAACC T TCAG TTG T TGCCAAACAAT TT TTAGMA CAACAT TAT TT TAAGGAG ATAAATAA 25 0?? amino acid sequence (SEQ ID NO: 58); MLRRSHFLQIFTLO_'ALLTISGCQLTDTRKPGRTT1R&7AQSSTESSIAN1VTELNHBELG-YNTTLTSNLG SSTV,'THQALLRGDADIAATRYTGTDITGTLGLKAVI(DPEEASRIVKTEQKRYNQTWYPTYGSDTYFMIVT KEFARQNI4ITK I SDL1KKLS'-TTMRAGVDSSWMNtREGDGYTDFAKTYGFEFSIII Y PNQ1GLVYDAVESNEIiMQVV L-GYSTDORI. SYhLETILRDDKKFPPYEASMVVNINS II KDPKLI KLLHRLiD-GKINLKTM.QNLNYN VDDKLL OR? DNA sequence (SEQ ID NO; 65): AkTGcT'TAAAAAATCGCACT'TTTACASATAk-TT.2"AcATTTGc-T TAGccc~cfTMJ' CAtT'TTGGTTGTO17A 35 TTAACOA3%TACTXkA. AAAGTCT'GOTOATAfCCACN'TAT~TAAGGTTGCTGCOCA-AG3TTOTACAGAGTCTA21GTATT ATGOM7ATATTATCAC.CGAA- TTAAT 'TCATOrACCAATTAGGATT AA.C~AOJ CTTTAA ITA'AGCAA' TCTTQGT .CTCTTCGGTTACTOACC,'AGOTTTOrCTCCGTGGTGATGO-TGAOATTGCTGC-CACAOAGTTATAOAGSA.AOA GACATCACAO3GGAOTCTTGGTT~uAGCTGTT AOACCTAAGAAGCTTCTAGATTGTAAAACT-AA TTCC AAAAAO-GCTACAATOAAACTTGGTATCCTAOCTTATGGTTTTTCTGATAOTTATGCATTCATGGTTACT 40 AGATGCACAGA? .7A~ -AAT -CACTAAGCATCTCTG ATCTTAA.AAATTATCAACAAO,'TATGA AGGCA GGOGTTGATAGTTCATGGATGA.ATCGCGAGGGAGATSGATACACTGATTTCGC-TAAAACATACGGT4TTTG AA TT'-TOACATATTTACO-CTATGCAAAJ. ATGGCTTAGTCTATGATGCGGTTGAAAZGTAAOAAAAGOAATCTGTA TTAC-GTACTCCACTGACGGTC-GTATTTCOAGOT'ATGATTTAGAAATTTITAAGGGATOGATPDAAAAATTC 'TTT O CTOCTTATGzAAGCCTCTATGGTTGTCAACA;ATTCTATCATCAAAAikPAGXTICCTAA' CTP-tXAAAAATTAOTC 45 CATCGACTCGYATGGTAAAjATCAtTTT LAAAACGATGCW ACCTTAATTAT ATGGTAGATGATAAkACrTTTA GAUCOTTCAT TGTTGCCAA%_CA.ATTTT TGAAAAAAOCAT TAT TTTZG GGAGATAAA'TAA O-R? amino acid seqence (SE SNO 9) MMLRKS .?LQ I FLOLALT! SGCQLTDTRIKSRHT Th J -AAQS STE SS1IMANI I TEL IXHNELOYNT TL ISN 4 -G S STVTI1QALLRGDA DIAATRYTGTDI TGT-'LL AVI.D iKEASK 1VKTEQ RYNQ'TW,,YPTYGrFSDTYAFMV',T' 50 KEFARQW1< I TNTSDLKKLSTTNIKAGVDSSWI4NREODGYTDFAKTYGFEFSH IYPM'Q1 GLVrYDAVESN4MQSV LGYSTD'GRI SSYDLE ILRDDKEFPYEASMVVNNS II EKDPKLMKLHP.LDGINLTMQ NLNYMV-IDDKLL EPSVVAKQFLEKNHYFRGDK Strain 1C458 55 OR? DNA sequence (SEQ ID NO:10 66), ATGCTTAAZAAAATCGCAOCTTTTTACAGATAT-'IT(ACCTTTGCTTAGCCCTC-TTAACGAT TTCTGG(TTGTCA.A TTlACGATAOf-TA. -AAACCTGGTCATAOCACAATTIAOGTTGOTGOCC4VAACTT0TACAGAGTOTA TATC ATGGC.AAATATTOTCACCGA lATTAATTC'ATCACGAATTAgGATACAACACAACTTTAATrzAG3CAATCTTGGT TCCTGTACGGTTACTOCACCAAG CTTTGO^TCOGTGGTGA 'TGCTGACATTOCTCCCACACGTTAT AOAGGAkAC.A 6 0 GACATCACGGAACTCTTOGCTTAAAA' GCTGTTAA ,AGACACTA.AAGAAzGCTTCT;AGATTGT~aAAAACTGA - 72 TTCCPAAACGC-TACAAPTCAAA CTTGCTATCCTACTTATQCTTTTT""~' ATACTTA'I0CATTCATGOT TA CT AAAgAG1'TTGCCAkGACAGA-,AtA.7-ATCACCAGATC TCTGAtCTCAAAAg TTATCAACAACTAT GAAGCCA GGOGTTGAT .CTTC'ATGG ATGAA TCGCGALGGGAGATGGATACACTGAtTT CGCTAAtYAACATACOGTTTTGAA TT'TTCAtCsgrTTTACCCTATGCM-AlTTGGCTTAGlTCTATGATGCAG TGk.TAACAZIAATGCAATCTGTA 5 T'TAGGCTACTCCAICTCACGGTCGTATTT CGAGCTAT GATTTAAA ,'ATTTTAAGGGATGA, TAAAPiAATTCT1TT CCTCCTTATGAlACOTCTATGGTTGTCAACAATXTCTATCATCAl~'2iAAGATCCTAU LCTAA~AAAATTAOTC CGrACTCGATGGT, AAATCAA,,TTTAAAAA.CGATCCA3%AACCTTAATTATAT GOTAGATGATAA ACT TTTA GAnCCTTCAGTTGTTGzCCAAACA.ATTTTTrAAAAAACCATTATTTTAAGAC)ATAAA4TAA ORF amino aicid seq.uenceP (SEQ -D NO: 60): 10 MLRKSRPLQI-FTLCLALLTISGCQLTDTKKPGXTTIKVAA.QSSTESSIMAzNIVTELIHHEELGYNTTLISNLG S CTVT1AQALLP.GDA'DleXVTRYTG TDITGTLGLKAVKDiTKEASK IVi{TE FQKRYNQTWY PTYGFSDTYAFMVfT KEF~lkQNKITE- ISDLKKLSTTMAGVDSSWMNREG'DGYTDP-AKFTYGFEEFSNIY PMQIGL YDAVESKI4Q'SV LG YSTDGRI ESYDLETILEOD: KFFPPYEASMV 7hNS II KtDPELKKLLHIRLDGKINLKT ZQNLtTYMVDDK LL EjSVVAEQFLEKNHYFICDK ______________________ Table 8, Amino.- acid and encoding DNA sequences of gbslOS7 proteins derived from different strains of S. agalueduee Strain 0176H4A 20 ORF DNA 5squence (SEQ ID NO; 735; TTGTTCAATAAATAOGTTTTAGAACTTGOrAAATCAGG.AAAG 4CTTTGQCTTTATATGGQMGTSCTAGGATTCA ACTATTAITTTTAGGrATCAA GTCCTGTA'TCTG3C TATGGATAGTGTTGG;XAVTCAAA7,GTCAGGGCAATGTTTTA GAGCGTCGTCAACGCGATGCAGAA;AACAGAAGCCA.GGTAATGTTC-TAGAGC-GTCGTCAACGCGATGCAG AA A ACAGjAAGCCAAG CGTAATGTTCTAGAGCGTC"GTCAACGTGATGCGGAAAA.UCAAGGCAAGTAGGTCAAC-TT 25 ATAGGGAAAAAATCCACTTCTTTCAAA.GTVCATAATCTAGAAAATAATCA CTCTAGTCAAGGTGACTC-T AACAAA2sCAGTCATTCTC TAAAAAAGTATCTCAGGTTACTAA&TGTAGCTA ATAOACCGATOTTAASC TAATAAT T CTAGAAOAjT T T CA.GT GATA~~PATAAT TACC TAUAACAGG T GA TGATCXAAT G TCA T T TTTAAAC T TGT A GGTTTTGVGTTTAsATTTTGTTAACAAGT COCTGCGGTTTG-GACCAATGAAA12ATTAA (-RE, amino acid seouenca (SEFQ IL NO: 67): 0 LF*NKIGFRTYJRSGIWLYNG1(VLCST II LSS PVSNDIISVNtQSQGNVL 7 ERRQ.RAENESQGNVLE RRQ.DAU NPSQGNVP.LERRQRDAENKSQVOiQLI OENPLLSKST ISRENNHSSQGDSNEQS FSKICV'SQVTNTVANRPMLTNN SETI1SVINKLPKTGDDQNVI FKLV FGL7 LT RCGLERNTEN ST train 12401----- ------- -------------- ----- --------------- 35 0 1FDNNO74) E D O' TTGTTCAATAAAA, TAGGTTTAGAACTTGGAAATCAGGAAA~rGCTT GCCTTTATATGGGAGTGCTAGGATCA nCTATTATTTTAS3GATCAAGTC.CTGTATCTGCTATGATAGTGT-TGAA ATCAAAGTC-AAGGTAA%.TGTTCTA CAOCGTCGTCAAC GTGnTOCGGATAACA,.AGCCAAGOTnATGTATCTAOAACCTCGTCAACGCIGATGTCGAA % AAC?.-AAGTCAGGIGCAA; TGTTCTAGAAC-GTCGTC-AACCTGATGT4TGAOAT ,AGAGCCAAlGGCAATGTTCTA 40 G^AGCO^TCGCCPtACGTOATGCAG AAA-ACYLk-VAAOTCAO-;GCTAATGT TCTAGAGVCGTCGTCAACGCGATGCnO-AT AACAAGS4JGAAGTAATOGT T CTAG AACG TCG T CAACG CGA T G TGGAAAAAG TCAG G.GCAATCGT T CT GCACG TCG CCCAAC GTCAT GTTVGAGAAIC AAGA GC CCAAG TAGG T C AC TTAT AGQGGtAAT C CAC T TCT T TCA AAGTCA.ACTrATATCTA'.GAGMAATAA'%TCACTCTAGTCA.AGGTGAC-TCTAACAACAGTCAT-rTCTCTAA-AAA% G TATCTCAGGTTACTAAPTCTAGCTAATAGACCAATQTTA ACTAATAA-TTCTAG-AACAATTTCAGTGATA AA;T 45 AADATTACCTMAAACAOCGTGA.TGATCMAAATGTCATTTTTAkAACTTGTACGGTTTTCGTTTAATTTTGTTAACA. AGTCGCTGCGGTTTGAOACGCAAzTGAAPAATTAA ORF amino acid seenc (SE Q 2pN:6?) LFNIIGFRTWRSGXLN ,LYNGVLGSTT I LGSSPVSAM DSVGNQSQG.NVLERRQ.<RDADNKSQGN VLERP3 DV1E NKSQQNVLERRQRDVENKSQGNVLERRQRD;AENKSQGNVLERRQRDADNKSQThWVLERRQRDVENKSQGNVTL 50ERRQRDVSNKSQVCrQLIGKNPLLSKST ISRENNHS SQGDSN .QSWS ZKVCQVTVANRPNLTNNSFT ISINt NLPKTODDQNVwI FELVOFOLI LLTSRCGLRRNEA [Strain BAA23 OR QAIe ene4SQ IDNO ) 55 TTGTTGATAkATGDTTTTAGACTT3GV~zATCAGGAAAGCTCTGGCTTTA-TATGGGAGTGCTAGGXIvCA. ACTATTATTTTAGOATCAACTCCTOTATCTCCTATCCATAGTGTTGAAXTCAAAPGTCAOGCCAATCTTTTA I GCGTCGTCAACOTGATGCPAAA.ACAOAAGCCAAG rGTA.ATGTTCTACA.zGCGTCGTCAACGTGATGCA GAA -73 AACAGAACCONA-GCTAATTC~ AGA'GOGTCG TCAACGC GAT GCIt . V2C..G CAGGTATG TC TA C ,GGTCGTCAACGTGATGTTGAGAA6TAAGAGCCA-AIGGCAzATGTTTTAGAGGGTCGTCAA7,CGCGATGTTGAG2 AiATAA'GAG. CAA;GGTAATGTTCTAGAGCGTC-GTCAACGTGATGCGGAAAACA.,AGAGOCAAGGCAATGTTCTA GAGOGTCOTCACGTGATGCGGI%A~A.hAOAGAG3C AAGGC.AATGiTTCTAGACCGTCGTCAACGCGATGCAGM., 5 AACAGAAGCCA GTAATGTTTTAGAACGTO-GS'CAACGC-GATGTTGzAGAACAAPGAGCCAAGGTA.ACGTTCTA GAGCGTCGCCAACGTGACGTTG7AGAACA3.AGGCCAAGGT.AATGTTTTAG AGCGTCGCC.AACGCGATGCGGAT A -,"-AGTCAGG.GC'A TGTTTTAGAGGGTCGCCAA %CGT-GATGTTGAGAACAAZGA"GCCAAGGTAATGTTCTA GAG CGTCGCCA. TATGTCCTATTAGAGTCAAATATGTTCTAGACGCGCCAAC TATG-GGAT XACGAGCCAGGGT.;ACGTTCTAGAGCTCGTCACGCGATGTQAGAATIAGAGOOAkAGGTAATGTTTTA 10 GAGCGTP-GrC-Th kPATGATG TTGAGAATAAGjAGTCAkAGTAGGTCAACTTATAGGG:AAAAA- TCCACTTTTTT-CA A-GTCAACTGTATCTAGAGAAAVTATCACTCT'CCX,2GGTGACTCTAA CAAAOtAGTCATTCTCTA-AAAA,. GTATCTC AGGTTACTAATGTAGCTAAkTAOA4 .CCGATO,.TTAAOCTAA3TAATTCTAGAACA.ATTTCAG LTG.T.AA~AT AAATTACCTAAAAUCAGGTGATGATC AAAA,'TGTCATTTTTAAACTTGTAGGTT TTGGTTTAiATTTTATTAACA ROTC TCTGCGGTT TGAGACGCAIATGAAAkATTAA 15 ORE amino &ciSeync (SEQ ID NO: 69) LFPNKNTGFRT'WKaG KLWL.YMGVLGSTI ILOSSPVSANDSVGNQSQG4VI ERkQROAENRSQGNVLSRRQRDAE NRSQONVLEFRRQRDJAENRSQGN VLERRQRrfVENKSQCNV;L E RRQRDVFENKS9QGNV LERE.QRDJ7EF 4ESQGNVL ERRQRDAENESQO -LERQRDAENRSQGVLERRDENKSONVPLRRQRDENSQGVIlLERQ)RDA.D NKSQGNVLERRQRDV ENRSQGUVPLERRQNN-VL £ESQDVPLERRRDADNKSQGN4VLERRQEDVENKSQGNVL 20 ERRQHIDVENKSQVOQLIOGKNPLESKSTVSRENNHiS SQOD)SNKQSESKKV-SQVTNVANiRPNiLTNNTSRTI EVIN, ELPKTGDDQN,-,VI FKLVGFOL ILLTSLClGLRRNEN -Strain COHI ORE DNA sequlence (SEQ 1D0- NO: --- 76) 25 TTOTTC ATAAAATAGOTTTTAG ACTTOOAAATC AGAAA,*,GCTTTIGOCTTTAT ATGGGAGTOCTAO GRTCA ACTATTATTTTAGATCO.,,TCCTTATCTGCTATOATATTTOAAATCAAGTCiAAGGTeAZTTTTA OAGCOTCGCOAAOGTGA.TOCGGAAAACi ,-iAAAGLTCAOGTAAJTGTT'TAiGAGCOTC'COiCCTA TCCGAA AAfCAAOiAGC-CAAOOO~zATOTTTTAGAIGCGTCGTCAnCGCOA TOTTOAOA) ATh-.AGCC-AROGCAATGTT~ T A GAO, CGTCGTCtAAOGTGATO3CGOAAi~'AACAAAA GTCAGCCAATGTTCTAOAGCOCCOCCAACOTGATGCOGA~T 30 AACAAGAOCCRAGTAG-OTCAACT TATROOOAAAAATCIAC TT TTTT-1CAAAOCCAAC TGTATC-TAGAGOLnAAT AA',TCACTCTAGTCAAGGTGACTCTAACRAAVCAGTCATTCTCTi1AARRAPGTATCTCAGGTTAC TAATGTAC -T rATAGACOGATGTTAOTRAtTA ATTCTAGAAC(,AAT -TIAGTGiAT. AA-AAATTAC(CTAR'.t ,AAGTO5G Gn(T CPAATGTCATTITTAAACTTGTAGOTTTTGGTTTAATT £'TGTTAyACAOTCOCTOCGGTTTGAGA )COCAnT GAAAAT TAR .35 OREF amino acid a~eaece (SEQ ID NOW 70) LFNqKIGFRTWKSGKLWLYNMGVLOSTI- LGSVNDVQQNLEQRANSG'ERRQRPE NESQGMLERRQRDXZNSQNV' LERRQRPAEN I300NVILERRQROA-DNKSQVr'QLI GKNPLFSK"PTVSREN ,Strain 1C105 ORE DNA sequ ence OSEQ I1D NO:, 7,7): TTOTTCAPATMAz4ATAOWTTTTAOAACTTGGAAATCAGGAAAGO-TTT G-CTTT.ATATGGGAGkCTGCTAGG(ATCC 5 actattar tttaggatcaaq toetgtttctCTATGATAGTATGAATCA;ATCAGGGCAATGT'ITTA5 45 1GAGCOTOGTCAACGTOATGCGGAAAA %CARGAGCCAA.G(CAA, TGTTCTAGAkGCGTCG 'TC.AAOCOCAT5CAOvA.A APACAGPAGCCAAGGTAA;'TOATCTAGAGCGTCGCCAACOTGA.CGTTGAGAACAAACCAAOGTAAC.GTTCT A5 GROCGTCOGTCAACOTO7ATOCAG-ATAAC,,AOAGCCAGO-CAATGTTTTAOAOCCGTCGCCAAPCGTGATG-TTOAO AA-CAAGPrOC-CAA.GGTAAWOTTCTAGAOCGTCOzCCAAAATAATOGTCCTTATTAOAGTCAAGATAATO-ATCTA GAGCOOCGCCAACGTOATGCGGATAA CAAGCOCCAGOTAACOTTCTAGAOCGCTCOCCAACGTGA TGT ZAG 50 AAPCAAOAGCCAAGOTAATOTTC-TRGAGCOGCCGCCAACGTGATGCOO.AT.AACAAGAOCCAGGGTAACGoT C GAGTGTCCGCCAACGTGATGTTGA?ACAPAACCAAOOGTAATGTTCTPACTCTCACTATCGGZIU AAC,4AOAOCCAAGGCAA-TOTTCTAGAGCGTCGTOAACCGCATG cAGAA"3AACAG AAG(CAGOTAAT' r C -A GAOCOTOOCCRACGTOACOGTTOAGAACAAGACCCAA(GTAACGTfTCTAGAOLCO TCOITCAACOTG3ATG1CtGAT~ AACA.AGAGCCAOO-'GCA.ATGTTTTAGAGCOTCGCCA.ACOTOA. OTTGAGA CAAOACCAAGOTAAkTG T- CA 55 GACOGTCGCCAAATAATOTCCTTR TTRRGAGTCAAOATAATGTTCTAOAOCbGCCCCC.PGTOATr G 'n £ .,AA;CAAOAGCCAOGGOThA COTTCTAGAOCGTCGCCA-ACOTCA'4TGTTOAGAACRAOROCCR? OOCAATGT T A CAOOGTCGTCAA-XCGCGATOTTOA~j'TA~ATAGTCAA' GTAGGTCAlC2TTATAGGOR,-AAATCCACTTTT TO? zAOTCRRCTGTATCTAOhA2AATARTCAC'TCThGTCA-AGGTGACTCTAACAA%CROfTCATTCTCTARAR~k GTRTCTCAGGTTACTAATOTAGCTARTAGRCCGRTOT JA.AC AATAAl TTCTAGAA'CAATTTCAG OATAzAI = 74 AA\VT TACCTAAAAC A GGTG AT GACCCPS'ATGTC AT T TTTA2'AQTTGTA'GGC-T TTCGTT TAAT T TTAT TA A~ AGTGTCT-GCGGTTTGA.GACGCAATGAAAATT.A ORF min acd zsquecze(SEQ ID NCO 711): LFNKIGFRTWKSGELWLYMGVLGSTTi GSVlIS~ISGVSRRAtKQNLRQ 5 NRSQGNDLERRQRDVENKSQYGNVLERRQRDADNKSQGNVLERRQRDVENKSQGNVT~LERRQNNV LXKSQDNDL ERRQRDADNKSQGMVLER- QR0VENKSQG1VLERQRDDNSQGV LECQRD EN{SQG-NVLESRRQ8QD KSTVSRSNt HSSQC3PZ-NKQSFSKKVSQVTNVrANRPMLTNNISRT isv i NKLPrGDDQNiV1FKLVIGFS LI LL 10 SLC-GLRRNEM Strain 1C458 OR DA _ IDNC:7EQID O 8): T TG T TCAA.TAJANI AGGT T TTAG AA CTT G G AUTCAGGAAliG CT TT GG C TT TATAT GGGAGT G CTA GG(,AT CA 15 A CWATTA TTTTA'GGAPTCAAGTCCTGTATCT GCTATGGATAGTGTTGGAMTCAAAG".TCAGG"'GCAATCTI TTA GAGCGTCGTCAAiCGCGATGTTGAG,7AATAAGrAG CCAAG-GTAATGTTCTAGAC-CGTCGTCAACGTGATGCGGAA ?AzACAAGCCAAGGCAATGTTTTAG3AGCGiTCGTCACGTGATGCAGAAAAkCAGAAVGCCAsAGGCAANTGT T Y'A G AGCGTCGTCAAC-GTGATGCPAAAACAGA.AGCCAAGzGCAATGTTTTAGACCGTCGTCAACGCGATGTTG AkAT~zAAGCCAAG2GTAAkTGTTCTAG AGCGTCGTCAAPCGCGATG'TTGAGAATAAGAGCCAAGTTTC -. 20 GiAGCGTCGTCAACGTGATCCGCA' AAACAAGAG.CCAAGCCAATCTTTTAGACCGT.CGTCAACGCGIATGCAAx .,TACAGA AGC,-CAACCCAATCTTTTACAGCGTCCTCAACGTGATCAGAAAA 1CAC ACCCAACGC ZAATGT" T m GAGCGTCGTGACGCATGTTGAAATA4GAkGCCAACCGCAATCTTTTGAGC3TCTCAsACGTGATG CAG Pz .ACAGAAGCCAACCCCATCTTTTAGAGCGTCGTCAACG(-rTGATGCAGAAAA,..CACAAGCCCM.GTAGG'TCrAA,( £T ATACGA ' AAAATCCACTTCTTTCAAA~iGTCrA.AT1ATATCTAGAGAPAAATAATCACTCTAG TCAAGGTGACTCT 25 A7 AAAACAGTCATTCTCTP,AAAAAGTATCTCAGGTATACAGTTAACTCAAAAAL1 T C'kAA ZCAATTTCAGTG A7AA.PTAAATACCTAAAA-CAGGTC-ATGATCA AAAT GTCATTTTTAAAC,-TICT-4 GCTTTTGGTTTA ATTTTGTTAACAAGTCGCTGCGGTTTGAG !,CGCAAJiTGAAAAr~T TAA 1,FNICIGFRTWI .SGKLW-yL, GVLG'TI IL.GSS PVSAMDSVGN4QSQGNVLERR>QRDVFENSQGNVIIRPQ RDAEtt ERRQRDAENKSQCNVLF2RRQRDi flNRSQGNVLERRQRDAEURSQGNVJLERRQ RDVENKSQGNVjLERRQP DAE NRSQGVLERRQRDAENRSQV,,GQLI GKUPLLSKI Ii SRENNHSSQGDSNKQSFSKKVISQVTNVAIRPM TNN SRTI SV1-NKLPKTGDDQNVIFRLVCrFGL1LLTSR.FCGLRRU-EN 35 Table 9: Amino acid and encoding DNA sequences of gbsl3O9 proteins derived from different strains Of S. agalacfiae Strain 0176 H4A ORF NA s, rie, (EC)ID NO : 85-) 40 TTTACT(3TAACCTATTCACAGTCTGAAC' GTAl,.CQTTGTTTTCTCTTTTGrAGAAA ,TA ACATTTAGTAGCA.GT CGCTGGACAAATGGCTTTGAAA %CTAGAkATACCAGTA.GATGACTGGTTAGGTCTTCnA %AAATATAACAGATAT TCI,%ATAGAkr)ATTCTTATATCA TGTTGCA£AATTG2 CTACA2ATC.ATGCC-TTATCCTCAAGTTTGCAAAG TAATALP GATAGCACTTTCCAA~.AMTCATAACAkAGACT-GTGTTTTAAAACCCYTAA-AATTTGTAG AAAATTGTTA 'AAGAAAAAG. AACGCTATCGTTTTTATTTGGAAGAGrCCA CCCGAACG-TAA. -AAnCTGAAAAAA %CTCTA GTT 45 GAGGGTGATGGACTCATCAkTTAAACCACAGATTCTACACAGGAAAGAAGGTA.TTTAGATTTA.ACACA'TTT GTTATTCATACAGGCTCAAAAAA- AGTTTCTA2CTAPAtAGfATATGnATTCCAGGACAnGCACGAeiATAWTAI CAG CTTAATTATG ATMkAGCTAAA,'TATAATCTTTTAGATTATATTTATAAzAACTATGAAGTAGATG AC A TAkCT ATTTTAATCACTAACTCTGATATGGGT AAGCT.ATACTAGT-A(3GTT'ETTAGGAATTAGGJAPiACCACT T AIAGG TAAAGAiAACA TGAGCCA T TTT TGG GATA7 C TAT CAT GT T zAAGAAAA T TAGT TCATACCT TAGAAAA 50 TATCOATTGAAmATPCCATTTTACTTTAATCGTA AATATATTCT-GATAAGCTTGA ATTACTT TTTGATACTGTTGPATCACTCATTTGTGA TCAAC-TIGAGATCA. ACTTTCA2GTTACAAAAAGTA TflAAATAAz TTTCAAATTThAAACCACCCATCTT ACAAA74TCTTTC-AAATCGTGCTATT-GGTATCATGGA.A TCACAACACAGAAAC ATAACCTATAGAATCAACCGCCTGGCATGTATTGGTCP-AATGGGGAZATCTCCACAI ATGG CIATATAT TAT AT TT GAAGC TACGG TT TAC GGAATTAT TT T TC GTTC TTG GAGAAG TA 55 TACAG T GAG TATAAAAG GT TCATT TAG TGCACGGCGACT T T T TAAAGAC AGAT GAAT TAATAAA T TT TCTAAGCCC-CTTCTAAAAA-2ATGGCAGAAAATGGAGTATAACAGGAATCAAAACAAAA TAG OF amino acidsisec (880 ID NO. 79): -75 FSVTYSQSERTV, VFS FOETITFSRSRW4TNGFETRI PVDU LGLEKYKRYS I EFLYHVAlKLA; TMMPYR,-QVCKFVI DSTLQTI I TK>CVLKAVKr-VEKLLKEKERYRFYLE EPERKI VKKLYVEGDQVXI KSTDSREERRYI;DLTHF5 V'LI TGS3KKV ST KRYELQDKIIE ILQLNYDKAKYNLLDY IYNIIYEVDDDT IL ITNSDNSGKGYTSRIVFKELGKAL KVKKHEHF'vDIYHVKEKLSSYLRKYPIES DFTLDAVKKYNSDKI$LVFDTVESLIQDELEDQEFQKFK KKV 5 Lt4TFKY KPALRNLSRGIGMES~I1 TYENKRRGMYWSKWGI STMANII I FERANGLRELFFe;SWRKV YSEYKEGSFSAGRLFKRTDELDKFSKPLLKNGREN' SITGI KTKj Strain 12401 ORF NA equece SEQID NO : 66): 10TTTAQTGTAACCT ATTCACAG'ICTGAACGXACGGT2'GTT TTCTCtITTT GGAQPAAATAAQXTTA-GTAGQAGI CGC TGGA CA.AATGGCTTTGAAAzCTAGAPATAC-CAGTAGATGAGTGGTTAOOTCTTGAAAAAWATAAG AGATAT TCAATAGPAATTCTT.AT.AT CATOT TGCAA.AATTGGCTACAATG AT GCC TTAT vASTCAAGTTTGCAAAGTAMkA GATAGCAOATTTGCAAA CAATCATAACAAAAGnACTSGTGTTTTAAt.AGCAGTMkAATTTG7CGAAAA TTGTTA AAiGAA GAACCTATCGTTTTTATTTGGAGAGCCACCCAACgTkZA,~AtGAAV-ddtCTGTATGTT 15 GaGGGTGATGGAGTCAT-A.TTA4AAAGCACAGATTCTAAGAGGA.QAAGGTT TTA(IATTTAACACATTTT GTTATTCATACAGGCTCAA;AAAAAOTTTCTACMAAAGATATAATTGCAGGCAAGCAOGA AATATTAAGk GTTrAATTATGATAAAGCTAAATATAATCTTTTAGATTATATTTATAATAAkCTATGAA-GTAGVATGACGATACT A;TTTTAATOACTAA.CTCTG ATATGSG -TA.AGGCTrATACTAGTAGA;PGTTTT TAAGG(AA.TTAGG3A,4AACACTT ?LAGGTAAAGdAACATCAGATTTTTGGGATATCTATCATGT t2AA;AAGTTAAGTTCATACCTTAGAAAA 20 TATCrOA7TGAATTACCGATTTTGCTTTAATGCGGTAALAAr.%hATCTCTGATAAGTTGAA ,TTAG T T TTTG.ATACTGTTGAETCACTG.ATTTGTGATAACTTGAAGATCAAGAATTTCAGAAGTTTAP.AGAAAAGTA TTTAAx'T TTTCA- TATATAAACACTCATCTTAAJAtTCTTTCA'ATCTGTA TTQGTA4CATGG AA T CACAACACAGAAAOTATAACGTATAGAATGAzAGCGACGTGGCATGzTAT1TGGTCAAG,(TGGGGAA24TCTGCACA% ATGGCAAATATGApTTAzTATTTGAAA GAGCT.2ACGSTTTACGAGAATTA TTTTTCGGTTCTTGGGkPIAGGT"A 25 TACAGTGAGTAT.kAAALGGTTCATTTATGCAGGCWYCTTTTTAg-TGACAQAC TGAATTATATAAAz'T-tW T CTA A GC CC CT TC T AAAA!A.T G GCs-AG' AAA T GAG A TA ACI:AG GMAAT CAAA AC AAA ATA G GEE amino ai ~ec SQI O 0 DSTLOT I I TKDCVIJKAVJKFVS KLLKEKERY RFY LEESPERKKV-KKLYVSG DGVNI KSTDSRE ERRY LOLIHF .30 VI HTGS .KVSTKRYELQDXHEI LQLNYDKN .,.YNLLDYI2YNNYSVDDDT ILl TNSDNWKGYTSRV'tFKELGKM. KVKKHEHFWDI YHVKSKLS SYLRKYP IELTDFA LDAI(KYNSDKLSLVFDTVSSL-IODELSFDQEFQKFKKKV L ~iNEKY IKPAHLRN LSNRGCIGIMESSR: ITYRMKRRGMIYWSKWSGI SETMANMI I FERA.NGLRLK-FGS4FK Y SEYKSGSFSAGF-LFKKTDELYKFSKPLLKNGRKNS ITOISTK ,5 jStrain 8AA23 ORE DN4A sequence (SEQ ID NO: 87) T TTAGTGTAACC TAT TCACAGTCTGAACGTACGGTT GTTT TCTCTTTT(;GA(2Al% TAACATTTAGTA-GAGT CGCTGGACAePJ&TGGOT TTG AAOrTAGAATACCAG TGAttTCTG'GTCGGTC-TTGATTAAAA 5TCAA %TAGAATCTTATCATGTTQCA~~TTGGCTA--TGATGC-TTATCECAAGTTTGCA;AGTAATA AAGAAGAAGOT'ATCGTTTTATTTGG-AGAGCCACCG-',-AACTAAVAAATGAAAPAACTGTZTGTT IGAGGGTGATGGAGTCAmTGATTAAAAGCACAGATTCTAGAGAGGAAAG AACGTATTTAGATTTA.ACACATTT GTTA7,TTCATA,'CAGGO(,TC AzAAAAAGTTTC.TA.CTAA? AATATAPATTCAGGACAAGO-AGAAATATTACA5 ICTTAATTATGAT.AAAG (CTAAAT-ATAATOT,-TTA;GA2TATATTTADThATAAGTTAJ AGTAGA6TG'. %CGATA-T 45 'ATTTTAA,'TQACTAACTCTG ATATGGS TAAAGGCTATAOTAGTAGASTTTTTAAGGAATTAGGAAA AGCkCTT 'AYGSTAAkAGAAA.CATGAGCATTTTTGGGATATCTATCATGTTAAAGM'.AAG~kTTAACGTTCATACCTTA-.AAA. 'ATCCAATTGAATTAACC'GATTTTGC-T- ±TASATGCGGTAAAAAA, ATATAATTC-TGATARAGC-TTGALATTAGTT TTTGATACTGTTG AATCAOTGATTtTGkIA GAAC.'TIGAG~ATAAGATTTCAAAGTTTAYGAAAi AAGTA TTAAtATAATTTOAAAi TATATAA AACC-AGCTCATCTTAGAAkATCTITAAAITCGTGGTIATTGGTATGATGQAA 5 0 TOACAAOACAGA.1.AAGATAACGTATAOAATGrt.AGCG ACGTGG CATGTATTGGTCAAA %GTGGG2GAATCTCCACA ATGGCAAATATGATTATAC TTGAnAGAGC TAACGGT TTACGAGAATTATT T£TT CGG*TTCTTSGACAAA.UGGTA TC TAA CC C CTT T APkAA TG G CAGAAATG ATAT ACA G GA'rA AAPvAAPA TAG ORE amino ac Te~ec SgI O; 81) 5 fSVTY 'QSERTVVE'-S FOR I TFSRSRM'INGSTRI PVDEW'LGLSRK KYS I FLYMV-%AKLATMIMPYRQVGKVI V I HTGSKKVISTKRYE LQ DKHSIT LQLNYDKAKYNLLDY I YNNYSVDDDT 1, L ITNS DMOKGYT SRVF-KSLGKAL KVKKHEHFW ,D1YHVKEKLSSYLRKYPI ELTDEALDAV ',KKYNSDKLELVFDTVESLI CDELEDQEFQKFKKKV~ LNNFKYIKPA}ILRNLSNRGIGI MESSQNRKITYRMUKRRGMYWSKWG I ETMIANMI ILSRNGLRD LFFGSNRKV 60YSEYKEGSFSAI2,'RLFKKWDSLDKFSKPLLKNGRKYWSITGIKTR - 76 Strain COWI ORF DNA sequence (SEO ID NO. 85): ATGGCAAGTTIAAAATCTCGGAJQAGATTTTGTA?1ATAA-TPAATAA, ATAA ,AACAGAAJAAMTTTTA, 5 AGTGAAnTTGAAOs(-AGTATG7 AAGCTATATCGGTCCTCAA ,ATGAGAAO-tiAGCTATAAGA4GA CAATOAG TCTG7AAOGTACGGTTGTTTTCTCTTTTGGA AAATAAC ATTTAGTA;GAGTCG CTGGAC -AAAiTGGCTTT4GAA ACTAGhA-TAOOAGTAGA 4 TOAGTOGTTAGGTCTTOAAA AATATAAGAG(ATATTOAA-vTAGA~pATTCTTATATO-AT GTTGCAAAAATTGGOTACAATGA.TGCCTTATCGTCzAGTTTGCAAAGTAAT3TAGATAGCACTTTCAA&AA'iC ATAACAA AAGAC TGTG-TT T TAAAAGOAGTAuAATTTGTAGAAAAATTGT TA AAAG-AAAAAGAACGCTAT CGT AAAGCAkCAGATTCTAGAG,'.GGj*AGA, AG TA'T TTZGATT T2ACACATT TTGT TTTCATACAGGCTCAAAP AAtAGTTTCT.ACTAA,. AAGATATGXATTGCCGGA CAAGCACGAAATA T TACAkCTATAGTAV~ TATA ATOTTTTAGATTATA2TTTATAATAACTATGAAGTAGA$TGAGGAT AOTA TTTTAATCAOThA-CTCTGAT ATGGGTAYAGGC-TATACTACGTAGATTTTTA;AGCAAkTTAGG TAAAGCAC~rTTAAPGGvTA'AAGAAACATGAGCAT 15 TTTTGGGATATOTATOATGTTAAAG AAA AGTTAkAGTIOATACCTAAAATATCCAAZTTGAAPTTAAPCCGAT TTTGCTTTAGATGCGGTAAA ATATAATTCTNTAGCTTGAATTAGTTTTT&TATPCTGTTGA TCAC-TG ATTTGC3TGCAACTT AAGCATOAAGAATTCAG7AAGLTTTAAGAAAAAAG-TATTAAIATAATTTC.,AAT.ATATA AArACCAGOTCATCTTAGAA-ATOTTTCAAATCGTGGT-ATTGGTATCATGGATCACAA,*.nCAGAA,4AGnTAACG TATAGAATGA AGCGACGTGGOATG TATTGGTOAAGTGGGGAATCT-CAC.A TGGCAA ATATCATTATACT 20 G.AACAGTAACGGTT-TACOC-. AATTATTTTTCCOTTOTTGOYAAAAGGTA,%TACAO TGAGTATAAA-OiGPGT TCATTTA GTGCAGGGCGACTTTTTAA.AAAG ACAGATGAATTA.GATAAATTTTCTAAGC CCTTC lAAAAAT 095 amino; acid, sequene 1r; I NO. 82): 25 TRI PVDEWLGLEKYKX S 1-E.FLYRiVAlKLATMMPYRQVCK /1 ODSTLOT IITKErDVLKAV:KFVEKLLKEKERYR FYLEEPPERKKVNKLYVEGOGVIKSTDSBRRYLDLTHFVI f-I GSK1(V STKRYhLRDKHE 1LQLNYD KAK YNLL DY I YNNY EVL)DDT T L I TNSPDMGKGYTSRVFKE LGKALYKVKKHEHFWD I YHIVKEKLSSY LRKYF I E LTD YRNKRRGMYWSKWCI STIANMitI I LERAN GLR ELFFCSWR~K'VYSEYKECSFSAG,(RLFRKT DELDKFSKPILLKII 30 (3RKSITGIKTR Strain ICIO5 SRI' DNA sequence (SEQ ID) NO: 89) TTTACTCTAkACCTATTCACAGCTCGAACCTACCCTT-GTTTTCTCTTTTCAAAATAATICATTTAGTACGAC .T 35 CGCTGGAkCAATGGCTTT CTAGTACCCAGTACTGATGTTAGTCTTAAAATAA~bACACAIAT TCAATACAATTCTTATATCATCTTGCMkAATTCGCTA.CA'ATGATCCCTTATCCTCAACTTTCAACTAATA GATAPGCACTTTG.CAAA~zCAATCATAACAA?2AC~TCT.GTTTTAAAAGAG..TA.AA-ATTTCTIAGM4A AATTGXTA AAk'G~A ,ACAACCTTCGTTTTTTTTGGAAACCACCCGAACGT,AAAAATG7A1AAACTCTATGTT GAGCTGATGGAGTCATCATTA,AACCACAGATTCTAGACAGGAkAAGAOCTATTTAG3ATTTAACACATTTT 40 CTTATTCATA CACGCTC 2 JA9,AGTTTCTC TAAAC-ATATAATTGIAGACAAC ACG;AAATATTAhC-AG CTTrAATTATGATAPACCTAAATATA ,ATCTTTTAGAflATATTTIATAATAAC(TATGAACGTAGATGACCA1TACT ATTTTAMTCACTAA'CTCTCATATGCUTAC' AGCTAACTAGTAGATTTTTmAACCAATAGAAA-AGCACTT AAGGTA'UAtACATGACATTTTTGGATATCTACCATCTTAAAGA.AACTTAAGTTCATACCTTACAAA TATCCAATTCA.ATTA-Af-COATTTTCCTTTAGATCCT -AAAJAJATATAAjTTCTGATAACICTTCAA 4TTAC7TT 45 TTTCA'TACTGTTCAATCAC-TCATTTC TCATGACT7AATCAAAATTTCAGAATTTAAAA2AGTA TTArATATNTTCA2%hTAAAA-ACCrCTCATCTTAAAATCTTTCAATCTGT-ATTG *hTC'TGCAA TCAQRACACAGCA~T-AACTATATA,3A.AAGCAC'TG,'CTG~fTATTCTCAACTGCCAA',T'C.TCCAP-CA ATCGCAA-TATGATTA TACTTAACOCTAACGOW-TTACCACT'AZTTTTTCCCTTCTTGAGAAACCT"A TACAI13GAGTATA~zAGCAAGGTTCATTTAC .TGCAGGGCCACTTTTAAAt'AGAC.AGATGOAATTAZCA %TAJ TTT 50 TCTAAGCCCCTTCT-AAAAVTCCCAGA,,ATGGATAT'ACCATCAAAACAAARTAC SRI' amfino3 acid seunc SEO0 ID) NO: 33) FI'SVTYSCJSERTW,?,FSFCE-ITFSRSRW4TNGFEW' I PVDE'WLGLEKYKRYS I EIYHVAKLATM MPYRQVCKV1,, DSTLQTl I TKDCVLKAV KIVEKLLKEKERYRFY LEE PPERKKVKKLiVECDCjVNI K.TDSRE EARYLOLTHI' 55 KVRKHIEhFWDI YNVREKLSSYLRKYPI ZLTDFALDAV KKYN$DKLELV FDTVESLICDZLEDQE'QFKI V LNeNFKYl KPAzRLRIL,SNRCIC IMESQERKI1TYF iK? RCMYWSKWG ISTMANiMIILERANCLRELF7FGSWR{V YSEYKEGSI'SAGRLFKKTDELDRFSRPLLKNGREWS ITGI KTK _____ Strain 1C458 60 !Rf DNA sequence (SEQ I D NO:i 90): -77 CPTTAGTGTAACCTATTCACAGTCTGAtC2GTACGGTTGTT TTCTCTTTTGGAGic AAT sACATTTAGTAGGAGT C-GOTGGACAAZATGGCTTTGAAACTAGAA3sTACCAGTAGATG AGTGSGTTAGGTCT TGAAAA-UATATAAGAGATAT TCAATAGAATTCT TATATCATGTTGCAM i~ATTGGCTACAA TGATGCCTTTCGTCAAGTTTGCAAAGTAATA GATAGCACTTTGCAAA,.CAAkTC~ATAACAAA.AGACTGT-GTTTTAAA%GC-AGTAA4AATTTGTAGAA,7ATTGTTA 5 AAAGAAAAAGAACGCTATCGTTT TTAT T2GGAA sAG CCACCCQAACGTA AAAAAAGTGAAAA,"AACTQTATQGTT G7AGGGTGATGGAGTCATGATTAAA-AGCACAG3ATTCTAGA(GAGGAAGWAAGGTATTTAGATTTAACACATTTT GT ATTCATACAGGCTCA- AAAAAGTTTCTAC'TAAAAGATATG(zAATTGCA GGACAAGCACG-AAATATTAC-AG CTTAATTATGATA. J\ GCTAA ATATA ATCTTTTAGATTATATTTATAA-TAACTMkG)AGTAG.rATu-GGATAC? nTTTTAA7ICACTAA3CTGTGnTATGGGTAAGGGTATLACTAGTAGAGTTTTT:AAGGIAAAGGAAAAGCAkCTT W0 A, GGTAAGAACATAGCATTTTTGGGATATCTATICATGTTA.AGAAAAGTTN4GTTCATACCTTGAAAAA TATCCAATTGAATTAA CCGATTTTGCTTTA(3ATGCGGT,3AAMAAATATA,TTCTGATIAEGCTTGAATTAGTT 5TTT GA APCTGTTGAATCACTGATT TGTGATGAAC TT GAfGAT-AAGjAATTTCGCAAGTTTA %GAAAZIAG(T A TTAAATILATTTCATWTAACGTCATC TTAGIITAATCT TTCA-AATCGTtG3TAT TGGTATCAT-riG.A TCACAACACAG P~AAATAACGTATAGAA TGACGC--GTXGG'C AT GTATTGGTCMAAGTGG!GGAAT CTCCAC A 15 'ATGGCAAATATGATTATACTTGAAAIGAGCT.ACGG TTTACGAGAATT'ATTTTTCGGTTCTTGGAGAAAGGTA, TACA.GTGAGTATAAAQAGCGTTCATWTAGTQGCAG GGCQACTTTTT;AAAAGrACA.GA',TQAATTAGATAAAITTT TC TA AGCCCCTTCTAAAAAATGGCAGAAATGGAGTAT3ACAGGnA TCAl ACAAA TAG ORE a. iag acid. 8sqec SE D O 4) 20 DSTLQTI ITECVLKAVRiFVEKLLKEKERYP.EYLEE EPERR K. %KLY IEGDGVMI EKSTDSREERRY'LDLT HF VIIATGSI{RVSTKRYELQDZHEILQLNYDKARYWLLDY1YNNYEVDDDTILITNSDMGRGYTSRVFKELGK-AL ,K' IEHEz'I9DI YEVKEKLSSYLRNYPI £LTDFALDNJ7 KEYNSDKLELVFDTVESLICDELEDQEFQKFRRKV YSEYKGSFSAF.LFKKT-DELKFSKPLLKNGRRWSI1TC1 EWE 25 Table M0 Amino acid and encoding DNA sequences of gbs1477 proteins derived. from different strains of S. agalactiac Strain 0176H4A 30 ORE DNA suence (SEQ ID 1NO: 133) A TGAAAAAA, ;tATCAk CPAATTTTTTGTGGQGTTCTCAG CGTTGTTAOTGATTTTAAQ GTQATTGCTCTCAGTT GCACCAGCOGTTTOOCGGOAAPAGAAPAAAAQAC TGAACTT CTTQCnTPA&ATTT TACA3%ATGATACA A.ACCTTAAG AATAGTGG-TTTCCCTG TACAAz AGGGO-TAO ATGGAACTGAATAT ACGGG.AGCTATTGAT AAA2%TTGGATAGCTACTTTGOCAMTGACT'-AAAPAGATATTGGTOGGG-CTTACTTTT4TTGGCAAATAG-AAG 35 G TG-AnTATATCAGCTGATAkTATAAnThi4TA. TAAQCT 'GAGTTTGGACACTCCAA -ACACC CTCAATATTAG TGAAGCTC-GTAGGTGGTTTO'mACAGAAGCAGGTATTAAGTTGAAA.CC4C TGGTTA AO7AOGGGTTTCCAGATT-ATWOAATTGAAACGACAAO-TCAAzCTTACTAA4."VTGGTGG-GGCCAT'TTGCWGAT TO'-AA.AAGC-GGTT'CAGTGAA~ ATCCTCTTCCATTOLATAAIACAAOOGATGGTGTTGTTAA7 AGATGCACACGTC TATCC;AAGAAxCACTGAAACz AAA CCGCAAATTGOACAAOA-ACTTTGCTGATAA AAATCTTGATTA TATIAAC. 40 AACCMAJ~AAGAC AAOGTAC'TTATCAGCAACTGOTTOGTO'rATGTTAuzAAAATACTGTTCGG7AC?2AA7 4ATC CTTAAAO GATCTGACTAT AATAA ATTAGTTTGGAGCGA TAGCATGACGAAA GGATTGACGTTTAACA-ACOAT GTTACTGTAC.ATTGAT-GGTCA?.A TTTTGJ-YACZYATCAAA ' TTAr-CCTTAGTACCTTAO"CA, AC-GTTTC OOTCTTGTCTTGAATGCAkACAGGTCTTTCTAAGTAGCAAAGCTGAAAkCAAzAAGATGTTGAAAzTCAAA ATCAA7 CTATTCAGrCWACAGTAAACOGTTC'-TACTGOTOOTT .SAAAA GTCAGAAA-ATAAzTGA3TGTOAAAC-TAO AT 43 TnTGCTAACAA CGCA ACAA',CTGAAAtACGAAl CACAAACWOGTAAtTCCAGTTAACAAEG.CAAA ,TCACAO,' TCGA 7AOA'CTTGGGCAO-TOOAT GGTAATGA AGTOTAAGGAGTGAAAA TTGACGCTSTCTTCAC~rGTOCAAP, GTTA AGATAOYTGACAAAkTGOGTGAAkTGTCGATTCAGCA.ACAGCALACAGCAGCA'ACTGACTTCAAt ATACA'YCT TTCAAAAAUCTTGOzATAATGCCAAAA -CTTACC-GTGO-TTAOAACOTGTTAOGOGCTACGOTCCAGCCTACOI T TCATTTGTGGGTGOAGTTGTOAQ-TATTAAGAATAA; CAAAAACTCAAA TGACCCAACTCCAATCAATCCATC-A 5 0 OAL.%CCAA AAGTTGTOACTTATGGACGTA- ATTTTGA AACAA-ATQAAIVGATGOCTOTGAA.rCGTCTAIGCAOGA GCTACTTTCCTTGTTAAGAACTCACAAGT2AATACTTGO CACGTAAAT IiGGTOTTGCAAl CTAATOAAGCT C C AGCAG TA AG A T CTATACACTGAAAG C TG T A GC T TATA ACAAA T TGA CTAG AA C-AACAAGA-AAGTICA.AGATGGTAAAGl ,CAGCATTGAATCTTATTGATOAAAAVACAAA,,CAGOTTACAAiTGAAIGCT TTTGCTAAAOCl AAACTACTCA' TATG AATTGGGTTGOTAOATAAAACGCTGCAA?'ACGT TGTTAAATTGATT TCT 55 A TA.AGCTGOTALTTTAAVATTCAGGTTTGAA31TGQAGGCGAGTAT £TTTGGAAGAOACTCAAG (ZCACO:-A AC'AGGT TATGGTAAATTGTCAAGTGATGTATCATTWAA %AGTAAkATGATA. CATCGTATAGOGAAGGGGCTTCA A-ATGATATTGCATACGATAAAG~rACTCC'rGGTAAA37 CAGT CACAA.ArGTTGTC-AC-AAA.lAAGTAACAATC CCACAACAGGTG1,GTA 'ITGGTACf-AATTCT' TTTCACA-k AT TGGTTTAAGCAT TAT GITTGAGCGGTAG;TT AT-CATGAMAaGAC-GTCAAPTCAGAGG AAGCTT 'AA 01W amino acid setqmence (SEQ ID NO. 91) MKKINT(FFVAFSALLL1 LTSLLSVA 'PAFAXEKSETT-ETVTLHFI LQT-DrRKNSMTGT-KGLDGTEYDGKAI D 5 KLDSYFQNDSKDIGGAYFI LANSKC3EYI1KANDKNKLKPSFSGNTPETTLNI SEAVGVGLTEENAGI EFETTO L RGDFQ1I ELKDKSTYNNGGAI LADSiCAVPVKI TLPLINKDZGVVKDAI{VYPENTETKPQJ DKNFADIQILDY IN NQEDKGT ISATVqGDV1{E YT*VGTKI LKGSDYXKCLVWTDSMTKGLTFNND. VTVTL.DGANFQSN-YTLVA ) DDQG.'F RILLNATGLSK'VPA,?AKTKDVE 'I i(INYSATVIIrGST; VFS'-EIIND.VKLDYGNNPT TENE PQTCNPV4KE ITVR. ETWAV :DGNE\1(-IGDEKVl DAVFTLQ1KOSDKNVN-VDSATATAATDVKYTFKNLNkAKTYRVVERV SGYAPAYV 10 SF100 FITIKNN NSNDPTPIN~PSEPKW?'TYGFFVETNQDGiSERL' AGArTFLVR, NSQSjQYLARESOVATNEA IAVTDAKVQLDEAVKAYNKLTKEQQdESQDGKAALNL 11DEKQ TAYNEA FAKANYSYEWdVVDKNIVfAFIWVLT S NTAGKFEI TGLWAPGEYSLEETQAFTGYAKLSSD'VSEKVNDTSYSEGASNDIAYDEDSGKTDAQK'NKKVTI 15 Strain 12351 OR DLNA. sequence uSEQ ID NO.' 134) A6TGAA1A'AATCACAATATTTGCAGTCTTCTCG(ThTTGCTEACTGACC(3TAVCATCATTGTTCTCAGTT SCA'CI2AGTGTTTGCG ,;GAAGC ^AAACTACTOACACAGTGACCTTGCAkCAAOATTGT CATOCCTCC~ACT OOATTTGACGGTTTTACTG-TGGTACAAAGGGTAAGG7ATAATA-TGA-TACGTTGT?,CAPATCGJ AQAC 20 CTTAI AACTTACTTTGGCTCAGGCGAOCGAAkAGAAAiTCGCAGGTGCTTACTTTGCTTTCASAAA STO;AACT GGTACTh AATACATCACTGAAAATGGTOGAr.AGTTGA'TATTTGGATA-AACAAOCCAAGGTGGTGCT GTTCTTAA -AGGTTTA" AC.AACAGACAA3TGSTTTCAAATTTAACACTTCTAAVTTA ACGAACTTAkCCAAATIC GTTGAAI TGAAAG-kA-ATCTACATACAACAACGAT%-GG TTCTATC.TTCTGAT TCAM-AGCA0TTCAGT T AAATCACTCTTCCATTGGTA-AACOACA2TGGTG TTT£A'AAGACGCTCACOTTTATCC.'-AAAG4 AACACrTGAAV 25 P AAACCA CAAGTAGATAAGAACTTCGCAG ATAAG"AACTTGATTATGC&ACACAAAA3sAGA.AA(GG A0CT0TCTCAO CAT0TGTTGGTGATGTTAAA-kTATCATT'TGAACA-A3.A2iCCTTAAAGGTTClGAC-TAT ACAAATT.AATCTGOACCOATAGCATGAC CAAAGGTTTGAOTTTCAACAIACGA.TATTGCTGThACATTGGAT GGTGCAPACTCTTGA TGC-TA'CAAATTACAAACTTGTA1%GCAGAkTGOCCAAGGTTTCCOCOTTGTCTTGACTGAC AA GGTCTT(LAGCAG'GCkAG.CCCGCAJUAAACAAPJ4ATAlGTTGA' AATCAAGA TCACTTACTCAGCTA' CT 3A TTCGl.GTTCTGCTGTCG TTGGTT CTGCf VICXTGAITGATTATGGATCGGC AACAzCCCAACA ATTG12,UAATGAACCA..AAGAAGGTATTCCAGTTOrATAAGAAATCACTGTTAACAAAACATGGGCAGTAGAT GGO-AATGAAGTGAA TAAAG'-CA-GATGAAACAGTTGAWPGCTG TCTT-rCCCTT!GA-AGT-T'AAGATGGTC-AL.k TGGGTGA'ATGTTGiATTCAGCTMA. GCAA-XCAG3CTGCAA..'CTAOCTTCiAACACACTTTTGP.hATTGGATAA'T GCTAAAACTTACOGCGTTATCGA ACGTG.TTAGCGGCTAGGCTGCAGAATACGTC TCAT TTGTAAA-TOGCGTT 35 OTAAOCATCAAGAAO2VAAAGACTAAATACC'ACTCCAATCACCCTCAGAO.CA %AAGTGOTG ACT WA-TGG,-ACG IAAATT-TGTGAAAA.CAATAAAGATGGAA AAGASACGCTTGGCAGGAGCTAC CTTC-CTTOTTAAO A.AAGnTGGCAAGTACT± GOCAOGTA,,ATCAGGTGTTGCACAGATCAAAAA ,VGCTGCTGTAGI t'TTCAAiCT AAlATCAGCATTG0AT00TGCTTTAA0CTTAC~ATGA TTTACTAAAGAA..AACAAGAAGGTCA-AGlzAT00TC, AkATCAGCATTGGCTACCGTTAGTG~AAAAAAGTTACATTGATCTTTGTTAACTA4CTAC-TCA 40 TAC0 AATGGTTGAAATA AT.TGTAAAATGTGTTAA TTATTTCTAACATAAA'GCTCAAJTTOAA ATzTA CTGGCTTGA CTGAAQz GTCAAtTACTCATTGGAAGVAACA2GCACCAACTGGTTATGCTAk T -TATCA GGTGA %TGTTTCGTTTAATGTTAATGCTACTTCATACAGTAAGGTT'TCCAACATATTGAG TATACCA GGTTCTAAAPACTAAAGATGCACAACA'AGTTrATCA-ATAAGAA~iGGTTYAC-TATW'CCALCAA.AQAGGTGGTATTGGT AC'AATTTTTTTCAC (AATTATTG GATTAAGTATrTATGCTTGAO-C'GTACTTPJA.,TGtT AAAAGACGTC-AATCA 4.5 OAGGAAGTTTPA ORF amino acdsTec.(E DNO: 92,) LKTF FSGEAKE IASAYFAFKNEAG7TKY ITENGEEVDTLDTTDM GGA',VIKGLTTD)NGFKF NTSITGTYQIT VEL KEKSTYNNDGYSI LADSKAV PVKI TLLVINDNO4CVVFDANVYJ?NTT FQVDKNFAD.EKELDYANNKKDKG 50 TVSASVG7rDVKKYL3VGTKI LKGEDYKKLTI WTDS 14TKCGTFNiND- IVTLDGATLDA~ltNYKLVAIIDDQGFPLRVLTD GNiEVNEAFDETVDAV FT LQ-VKDGDKWNVwDSAKATAATSFKXTFrENLDNAKTYRVFIERVSGYAPET Sr-vNfGV VT IENNKDSNEPTP 105PrrIPK.TYGRKFV ,;TNKDGKERL AGATFLVJKKDGKYLARKSGViATDA ZKPJWDST KSALD -AVKAYN4DLTKEKQEGQDG3KSAqLATVSEKQKAYI DAFVKAN4YSYENV7EDKNTAKNTVVKLI SNDKGQFE 55 ITGLTEGQYSLEET-QAFTGYAKLSGDVSFN']NATSYSKGSAQDIEYTQGSKTKDAQQVINKKVTI PQTGGIG ITIFFTI IGLSIMLGAVvVIMKRRQ SEE V _________________ Strain 12401 p - ------------------------------------ - ----- 7 -79 ATG; AAAG AATCAACAAATATTTTGCZAATGTTCTCC3GCATTGTTAITThSATTTTXAiCATGGTTGTTATCGGTA GCTCCGGTATTT GCTGCTGAGATGGGAAATATCACTAAAACAGTAACCTTACA-AAA'AT TGTTCAACATCC, GATAATTSGCTAGCCArATTTCCC GAATAjATGGATTGA.'TGAACGAG.CTATATGGSTCA ACTT ACTGACATTTCAGGATATTTTGGGCAAGGTTCTAAA2G2%AATCGCCGGTGCTTTCTTTGCGGTTATCAkATGA 5 AGTCAGAC-AAISA-TATATCAC AGAAAGTGGTACTG AAGTAGAAPAGTA TCGA31TGCAGCAGGTSTCCT TAAAGGT TTGACAACTG&AJXACGGCATTACATTTAATAQTGCAAAG-k(TTAAAAPGGA ACATACCAFAATCGQTTa .GTTGC-TT G AC AAT C TAA T TAT AKAAAT GG T GACAAAGT TC TT GC T GAC T C PAA.G C TGT CC C A.GTG AA.AT CA CTCT CCTTTGTATAA CGA.JXGA.AGGAATTGTCGTGGACGCTG-AA GTGTATCQA 1AAGAATACASAAG.AAGChCCAQAA; A T C GAC -A AAT T TGC T AAG GCAAA TAAT TCGT TGAA.T GAC AGG A TAA TT CAC T A TT G cAG T GG G GCA 10 GACTACGACAAATATCAGCCAG AAAilAGCAAAGC-TACTG-TGAAPTCGGTCAAGAhATCCCTTAC-GAAGTT A-AACAAAJZT C CAAAGGG TTAT A CAAAkC CTTT G CTG GTCATAC CA TG T CAAATG G TTTGAC A ATGG42TAAtCACTGTTAACTTAGAAGC-AT £TCAGCTCTTTTTGAA G:TACAA7 TTA.CAATSTTC l.ACC:T GATC3ACCGTGGTTTCACTTTGAATTCACAG-ATA CAGGTTGACAA;CTACPAAAGAGCGGAAA CACAA GCTGTT GAAT TCACATTGACATATAGCGCAAP.tiCTTAACGGTCGCTATCA'TACAGC'CGAAC,,CAAT 15 C.ATATCAAAQCTehAATACCGTAA CAA ACCAC-GT AAAAAGTA-'AAGAA6ATCCCAGTAAPCAC-CGTCAAATGCC GA T CA-T T TACAAAC TT GGA CAAAGG~TC'SA TTIG A GAA TCGAA TG T T GTT TATAC C-C TTAAA GATGGTGGAACAGCTGTTGCCTC-AGTTTCATT3ACAAAkAACAkACACCAAATOGCG;aAIATCAACTTAGGTAAT GCTATTAAATTTACAGTTACTCGQAGCGTT3QCTGQTAA~l.zTTCAGT5GTCTG.TGATAGTAAk7ACATACATG RTC TCAGAJACGTATCGCTCCGTTATGGTAATACAATCACTACTGGTGCTGQ TAGYTGCASMC TATCACCAATACT 20 CCACATTC-AGACAACCr- CAACAC 3&Cfl'AATCCAAP CTGAA7sCC-AK GTTGTCACACACGGTAA lAAA-ATTCGTC AAAACAAJGTT-CGYACTG -AACAAACSCTTGCAAGGTGCACAGTTCGTTG TTAAAPGAT4TCAGCTGGTAAATAC CTTGCATTG AAATCX ,ICTGCGACAA2%TATCAkGCTCAAA.CAAiCACCTTA-'CACAA ATGCTAAAlACTGCTCTTGApC GC-.TAATCGCA CTACA-ACAA ACTTTCAGCAGACATCAAAIAGvTAC42AAGTGAJAACAGCTAAA-ZGCA GAAAPTCAAAUCTGCTCAAQACGC TTACAAWGCAGCCTTCAT0' TAG4CTCGTk2l'AGCTTACGAGTGGGTAACT 25 AATAA AGAAGATGC TAACGTTGTTAAAnGTGACTTCAAC-GCTCACG(3TCAATTTQAAGTTACGCGGTCTTGCA' ACT G G TGATTATAAC TTGPJGCVACAAGCT C CAC-C TGG TT A C G CAT TA G CAGGTSGAT GTTG AT TT C AAA T TSGG AAACACT CAAAA GC AGA CGA C TCAG GT A.ACA T TCA TT ACAC TG CTA GC 2CAATFA-AAAAAAC G C TCAAC GC A TAGPA.AAC AAkAAAG TG A CTAT TCC"AC AA-A AGG TGG TAT TG GTAC ANTT CT-1T TCACA AT T ATTCCTTT.,SiCATATGCTTGGGCGGTATTATCATAAAAt. GACGTC ATCAAPGGAAGCT TAA 30 OR nioacid se-unce(E ID NO. 93) MK~fIKYF JSLLLILT~L.SVPVFAEMGaflTVTTLMKI VQTSDNLAEKPNFPGI NGLNGTXYM ;GQKL TDIMSGYFGQGSKE IAG AFFAV14ANESQTKY ITESOTEVESI1DAkAGVLKGLWTENGI TFNTANJJKGTYQ IVELL D)KSN4YFtI NSDKVIADSKAP V?VKI TLPLYNEECI VVDA-EVY PKNTEEAFQI DKN FAKANKLLNDSDNSATACGA DYDEYQAFKlAKATAEISQEI PYEV KTKIQEOSKYKNLM ,-WDTMSNGLTMGNTVN-LEASSGSFVJEGTDYINER 35 DDRGFTLKFTDTGLTELQKZEAET.QAVtEFTLTYSATVNGAAI DDKPESNDI REQYGNEPGKKEVEE I PVT PSNG E 1TVSETWDKGSDLENAAV14,tVYTiLKDG GTAVASVSLTKTT PNGE INLGNGI EFTVTGAFAGKFSGLTDSKTYM I SERlAGYGNT ITTGnGSAAITNT PPSDI4ET PLNPTE PKVV'TSGKFVKTSSTETERLQGAQPWMKDSAGKY LALKSSATISAQTTATNAKTALDKAAYNKLSADDQKGT GETAAEIKTADAYNAPFVlARTAYEWVT NKEDkANKVTSN4ADG-QFEVSGLATS DYKLEETQAPAGYAKLAGDVDF'KVG7NSaKAD)DSGNI DYTAz SNfKD 40 AQRlENKKVTIPQTGIGTILFT1IGLSIMLGAVII IKRRQSE&,A _________ Strain 126H4A ORFlDNAQ:QIDO-13): L4GA AAAkfAATG,'AACiAAATAT'TTGCAL;TCTTCT',CGCCTTGCTACTGCC(GTA ACATCATTCTCTCAS TT 45 GCACGAGCGTTTCCGGACGAA GCAA CAACTAATACW3GTGACTTTGCACAAkGATCTTC 7 1ACTGAATCAAAT Cj TZtATAAAGTAACTTCCCAG, GAACTAC-ACGCCTTAACGGAGATGACTATAAAGGTG-AA TC TATTTCTGC C rTTQC'TGAATACTTTGG(ATCAGG CTTC TAAA.AATTGACGGTGCTTTCTTTGT-ITTGGTTTAG-AAGAGAA, ~AAAGATrGGTGTCGTACi7AAT 4 TC-TTAAGC CAAALGCAATGACAAATTA ACACC-AGZACTTAATTACTAAkAGGT AC(ACCTGCAA C.AA.CAACAAAAGTTGAAGAA1,.GCTGTAGGTGGTTTG7ACAA ,CTGGTACGGGTATTGTTTTCAAT -50 ACAGCTGGTTTGA AAGGT AMTTCAAAA ,TTAA TGAATTGA4AACAAATC.AACTTACAACAA-T.AATGG-TTCC CTCTTAGCAGCTTCAAA-AGC'AG TTCCGGTGAAArATC-ACTCTTCCAPITTGGTAAGCAAAGATOGTGTTGTTA GAi GCACACGTTTATCCA-nM'GACCTGAACM.(.AACCAGAAGTAGACAGAtCTTCG-TAAACAAACGAT T TGACA ,GCTCTCAAA; GACGC TAG TCTTCTTA AGGC-TGGTGCAGACT-ACAAAAzACTATTCAkGCGAC'TAAAOGCT ACTGTh7ACAGCTGAAAZL;TCGGT AAGTTXTCCCTTAl'CGXAGTTAAAC;AAAGTT-CTTAAAGGTTCTAA ATAC 55 GPAAAACTGGTTTGOACCGATACCATGTCAA ATGGTTTGAPCAATGGTGATGATGTTA- ACCTTGCAGTTTCA; GGGAOTACAAiCAAC~rTTTCATTAAAGATATAGATTACAtCTCTTAGCATTGATGACCGTOGTTT~CAT~ ITGAAAX TTCAAAGCTACTGGn' TTGGACAAAUTTGGPAGACAGCTAAAGCATCTGoATGTTGA.ATTT ACATTGA CTTnT ^AAGCTEACTG-TAATGGCOAAGCA ATTATTGACAA4CCC-AGAAGTCAATG.ACATC.AA.ATTGGnCTATGGTAAT iAACCTGGTACAGATTTATCAGAACAA: CCTGTOACAC^TGAAO ATGGTGAAaTTAAAGTCAC TAkA.ACATGG 60 G CAGCAGGTGCTAATMkAG.-CAGACGCTAAAGiTTG7TCTA CACACTTA-AAAt'TGCTACTAAACAAGTCGTAGC-T -go TCGC~ ' CA.GACCA-A3-AGTCA TAATCTTGGTAAACAGCATGA CC T TTGAAATCAkCA GA2GCTTTCTCA21GGTAC-ATTCAAA6,GCCTTC.ZnAATA.AAGCTTACAQ-TGTTTCTAACGTQTTGCAGTTAT" AC TAATGC-TATTATGTACTGGTAATG-TTGCTATCACCAATACACAGACAGTGAAATCCAZCGCCA CTTACCCAACTCAkACCPkAAAzGTG .AA-ACAATGGCTAAGAA7,-ATTTG5TCAAGTTTGGCGAY~4TGCAG ATGCCCGC 5 TTAGCTGGTGCACAAkTTCGTTGTGAAAAPATTCACCTGG h AATTCC TTGCTCTTAAACA~rAGATGCAGCTGTA TCAGGAGCTCAA-ACTGAATTGGC-AACTGCTAAAA ,CAGSACTTQGATAATGCCATCAAAG CTTACAA %CGGTTTG AkC;AAAGCGCAG.CI 4 AGAAGGTC;TCTGATGG TACSITCAGGPAAAGAACTTATrCAACA2CTALlnCAGTCAGCTTAC QAC-GCAGC-CTTCATCAAAG CCACOTACAGC TTAT-ATATGOGT AGATGAA.'-AAACTPAA(32'CTATTAC( CT'OACT TCAAATMATCAAOQGTCAAkTTTG ACTTAC-TGGTCTTGAAGTACGTTCTTACAAOCTTAAAAAV,.CTCTTCCA 10 CCAGCAGGTTATIGCTAAATT42TCACGCGACATTGAGTTT ACAGTTGGAOACCATTCTTACACA.AGTGGTGAC ATCAACTACAV ACCAGATQ.ATGC-TAGCAACAATGCAC, AAAGTTTTCA ATM'1AAAVAGTAAICCATCO ACAAt ACAGGT GGTATT GGTACAATTCTTTTCA',CAATTATGGT-rTTAAGCATl-hTCC-TTGA ,GCG GTACT TATCA'.T-G 2 AAAGACGTCAATCAGAGC-AAGCTTlA ORF amino acid sequence (SE.Q ID NO: 94), 15i MaKKINEYEAFSALLLTVT SLLSVAPAFATYEATTNlTVT LHK ILQTE SN~lK SNFTGTT G ON;GDDYGS STS.D LAEYFcSSGSKE IDGAFFALALEEEKDGV, VQYVKAK AJDKLT FELl TKT FATTTKVEEAV GGLTTG TGIVFN TAGL-KGNEZK1 1 E'LKtDKSTYNNNGSLLAASRAkVPVKI TLFLVSKDGV JKDAftVYPKNTETKPEVDKNFAKTND LTAL-KDA TLLKAGADYKN, YSATRATVTAE1OGKVI FYEVKTKV.LKGSKYEKLVWeTDAY1MSNGLTN'GDDVINLS GTTTTFI EDlDYTLS IDDRGFTLKFKaTGLDKLEAAkKAS-DVEF -TLTYKATVNGQAI 1 EN P2EVNiDI EfLDYGN 20 KPGT DL SEQPVTPEOVVKWAA~DKVT ;NTQAVL DTKGT IUNLGKGMTEFE 1T GAFSGTFKCL QN&KAYTVSERVJAGYTUAINVTCNAVAI TNTFDSDNPTPLNPTQPV'EROGKK-VKVjGDADAR IAtGAQF-rJKNSAGRFALKEDAAVSOAQTELATAKTDLDNAl KAYNCLTKAOQQEGADtLGTSAKEL1NTKQSAY DAATFI KARTAY I 'V ETTAI TFTSNNQCQFEVTGLEVG--SYKLEETLnPAG-YAKLSGDI EFTVCJ4DSYTSGD I KY .TDOASNNAQKVFNtKKVT IFQTGG 1GT ILFT1 .IGLSIThLGAVNVI M4KRRcQSEEA 25 Strain 49447 ORE DNA sequence (SEQ ID NO: 127i) ATGAAAAAA.ATCAAZCAAATTTTTTG3TGGCGTTCTOA!GCGTTGTTAC,,TGATTTThACGTCATTGCTCTCAGiTT GCACCAGCGTTTGCCGr ~A GA)ACAA-7Cll;TGAGACTGTTOTTGCATAATTTACAAACTATACA 30 AACCTTAAGAATAGTGC-TTTCCOTGGTACAAAAOAGGGCTAGATGGAACTGAPATATGACGGG.AACcTATTGAT AAkATTGGATAGCTAOCTTTGGCAATGACTCAIAAGATATTGGTGGGGCTTACT'TTAT ATTGGCAA; ATAGCAAG OGTGAA.TATATOAA~GCTAAITGATAAt. d\TAAA-TT.kAGCCTGAGTTTAG7TGGGAAC.ACTCC-AsAAC40GACC CTCAATATTAGTGAMGC-TGTAGGTGGT TTGACAGAAGAAA.ACGCAGGTATTAAGTTTGA3%AACCACTGGTTTA AGArGGGATTTCCAGAT TAT TGAATTGAAAGACAAG-TCAACTTACATKAATGGTGGG GCCATCTTGGCTGAT 35 TC)AOCGGTTCCAGTGAAATCACT.CTCCATTGTAAC!AGGATGGTGTTGTTAACATGCAkCAC^GTC TATCCAPAAGAACAC-TGAAtACPAACCGCA AATTGACAAGAAC-TT TGCTCATAAAA-zATC'TTCATTATATTAAC AA-;CCAAAAAG.GAAAG TA'CT-ATATCAGCA iACTGTTGGTG-ATrGT-TAAAAAA*jVTA'TACTGT TGGG ACAAAAATC JTAAAGATCTGACTATAAAhJAAATTA,-G TTGACCGATAGATG'CiAAAGGATTGACGTTTVAAACG.T GTTACTGTAAQ-ATTGGATGGTGCAAA TTTTGAACAZATCAA.ATTACAzCCTTAGTAGCTGA! TGP ,ACCAAGGTTTC 40 CGTCTTGTCTTGAATGCAACAGGTCTTTCTAAAOATAGCAGAAGGCTGC ,AAJ 5 CAAAA vGATGTTGAAA-TCA. A ATCAACTATTCAGCTACAGTAA.ACGGTTCTADCTGT-GTTGAAAGTCtfSAAAATAATGAT3TOAAACTAG AT TATGCTflACAACCCQIACAAC TGAAAACG AA'CCAOAAAOITGGTAATCCAGTTAACAAAGAAATC-ACAGTTCGA AAGACTTGGGC-AGTGGATGGTAAnTGAAG-TGiA.ATAAr GGGAGATGpAAAAA-GTTGnCGCTGTCTTCACGTTGCA GTTAAAGA.TAGTGACAsAATGGTmGAATGTCIGAT CAGCAACAGCAAOAGCAGCAlCTGACTTCAkAATAkCACT 45 TTCPJAAACTTGGATAATGCCA-AACTTACCGTGTTGTAGA-ACGTGTTAGCGGCTAC GCTCCAGC'CTACGTT TCATTTGTGGGTGGAG TGTGACTATTAAGzAATAAC'AAAAA-ZCTCAA-ATGAkCCCACTCCAAPTCAA%-TCCATCA ' GC-CCAAAAGTTG'TG-ACTTATGGAC"GTAAe"ATTTGTGA'AAAATCARCATGGCTCTGA-ACGTCTAGCAGGA GCTACTTTCCTTGTTA' AGAACTCACAAGTCAT CTTGGCACGTAATC %GGTGT TGCAACTATGAGCT CACAAAGCAGTA ACAGATGCTAAA3GTAC-AACTGGATGPAO 'CTGTAAAGCTTATAACAAATTSACTAA.AGA.A i CAAC-'A5GAAG TCAAG TGG TAAG CAGC ATT GAATIC TTAT TGATrAAAAkAC;AAC.AG CT TACAAT GAAGC T TTTGC-TAPAGCAA.ACTAC-TCATATGAPATGGGTTOTAGATAAAAACG3CTGCACGTITG'TTjlAXTGATTTCT A-ATACA--GCTGGTAAAVTTTG;AATTACAGGTTTGAPATGOAG GCGAGTATAGTT TGGAACAGACTCAAGCACCA ACAGGTTATGCTX~kTTGTCA%-GTGATGTATCATTTVbGT'AATGATACAT-CGTATAGC7AGGGCTTCA AATGATATTGCA TACG7ATAA AGACTCCGGTAAAACAGATGCACAAAAIAGTTGTCAAC-AAA..AAAG~TAlAAATC 55 CCACAIA.ACAG(TGGTATT(R-GTA.CAATC;TTTCACAiATTAiTTGGTTTAAZGCATTATGCTTGGiAGCGGTAGTT ATCATGAAAAPG.ACGTCAA.TCAGAGGAAGCTTAA ORE amino acid- seyne E D NO' 9 5h MKK1NKFFVAFSALLL1 LTSLLSVAPAFAkEKEKTTE!TVTLfIKI LQTD--TNLRN'eSAFFGTKGLDG TEYDGKAI 0 KLIDSYE'GNDSKD1GGAYFI LANS~EEY 1 AN7DKNKLKPEFSGNTPKTLN I EAVC.CLTEENAGI KFETTO:L 60 RGDOI ELK DKSTYNNGGAI. LADSKAVVMI IT LPLINKDGVEDAH-VY PKNT ETKFQI DKUF.ADKNLEDY IN NQKDKGT ISATVGDV: EKYTVGTRI LKGSDYKKLVN" TDSt4TKGLTFNNDVWVT LDGANFEQSNYTLVXIDDQGF RLVLNATGLSKVAEAAT KDVE 1. RI NY SAT vTIGSTWrlEKS ENN DVKLDYGI, NPTTENEPQTGNPVNKE I TV?. RTNAVDGNEVNKGDE'NDA VFTLTQVKD,'SDfKV}VDS ATATA&AT DFFKY T F.N LDNMTY RPERV SGgYAPAYV SFVrGGWJT I NNEESNDPTP-21 NPSEPKV9VTYGCRKFV' KTNJDGSERLAGAT FLVKNSQSQYLAR{ SGVATNEA .5 NK.AVTDAKVQIDEAVKAiYNKLTKEQQESQDG:KAALNLI DERQTA YNEAFAK.ANYSYEr 2VVDKNAANVVK,1 S NTAGK FEI-'TLW EYSLEET QAPTGYAKLSSDVSrkVINDTSYSEGASNDIAYKDSGKTDAQKVVtIKVTI PQTGG^IGTILFTI IGLSINLGA-VVINI{RRQS5EEA Strain 509592 to ORF DNA sequence (SEQ 1D NO: 138): ATGZA~rAAAATAACAAATATTTTGCATGTTCTCGGCA.TTGTTA-TTAATT'-TAACATC-GTTGTTA.TCGGTA GCTCCGGTA TTTGOTGCTGAGtCATGGGTATCACTAAACAGTAICCTTCACAAATTGTTCAAIAC. .TCC GATArtTTTGGCTAAGzCCA,-ATTT-CCAGGAAA AATGGA-TGrATGA.3CGAAGTATATGGGTCACIA4ACTT AC-TGACATTTCAGGATA TTTTGGGVC-3AGTTCTA.ZAAAAATC-GCCGGTCCTTTOTTTGGGTTATGAATGAA2 15 AGTOAG'AOAAAA.TATATCACAG;AAGTGGTACTGAAGTAQ~AAGTATCATGCAGCAGQTGTCCTTAA QGT TTGA'4CAAC-TGAA ACGGOjATTACATTTAAkTAC TGCA-2ACT-TAA;%AAGG-AACATACO, AATCGTTGAGT-TGC TT GAO PJ.TCTAA-,TTATAAlaAATGGTGACAAGTTCTTGCTGAOCTCAIAAGCTGTCCCAG TGAAl AATCACTCTT ATCGA CAAAAAC TTTGCTAAAGCAA7ATAAFATT-GTTGA ATGAO GTGATAATTCAzGCTATTGCAGGTGGGGCA 20 GACTACGA CAiAATOAGGC'AGAAAGiCC AAAGTACTGCTGAA.P-ATCG GTCnAGiATCCCTTCGAAGcTT AAAAL74CAAA2AATGOCAAAAAGG GTGTAAA1TAO-AAAAACCTTG CTTGGGTCGATAC CATG'TC'-AAA %TG GTTTGACIA ATQGGTAAC2ACTGTTAAC TAGAPAGCATCGTC AGGC-TCTTTTGTAG AAGGTAACGATTACAA2 TGTTGAAO-GT GATGAOCGTGGTTTCACTTTGAAA T TCACAGATACAGGTTTGACTAA'GCTACAAAjAAGAA GCGGAPA-CC GCTGTTGAATTCIAOATTGACATATAGCGGAAOAG4,CTTAACGGTGCGGCTATTGATGA CAnGCCGA;AGCAAT 25 G ATA TCAJAAC T TCAAIYAC GC-TAAOCAAAC CAGGT A-AAAAA,.G TAAAAG AAATC C CAG TAACAC C GTC AAT GGC GAA- TCACTGTTAGCA; AACTTGGG ACAAPAGGTTOAATTTAAGAATCCGAATGTTGTTTATAC-CCTTAAA~ G AT GGT G GAAOAGC T GT TGCOC TAGTT T CAT T GAC AAAAPC AA.C A COAAAT GG CGASAT C AACT T AGG TAA T GGTATTIAATTTACAGTT CTGA ^GCGTTTGCTGGTAATTCAGTGGTCTGAITGATAGTA.2AACATACATG ATCTCAQAACGTATCGCTGGT TATGGTA.ATACAATOAOTAO.VTGGTGCTGGTAGTGOAGCTATCACCAATACT 30 C CA GAT TQCAA C AQCC AOCACCT1AC TCAA C T GAA C C JAGT G TGA CACC GG TzLAAT T CGT C A.5ATh.AAATTCGCTGMkAC.-AGAACGCTTGCAAkGGTGCACAGTTCGTTCTi'T MAGAT TC.AGCT(GTAAA %TA'lC C TrGCATTGAAA.TCATCTGCGACAAT ATCAGCTCAAAzCAACAGCTTACACAA ATC-CTAAACTGCTCTTGAZC GCTM- A)ATCGCGCCTTACAjCAACTTTCAOAGA,-GATCtAAAGTACTA-AA'GGTGA AACAGCTAAA I.CCA G,?AATICAAAC'TGC-TC AAGACGCTTACnATGCAQC (CTTC-ATCGTAGC-TCCTACA-.GCTTACGrAGTGGG('XTAAC T .35 AATAAAGALAGATGCTAA ,CGTTGTTAAi~GTGACTTC-AACGCTGk CGGVTCAATTTGAAGTTAGCGGTCTTGCA ACT GGTGATTATAkAACTTGA',AGAAACACAACCTCCAGCTGGTTACGCTAAATTAGCnGGTGATGTTG ATTTC AA4TTGGAAAi CAGCTCM2AAGCAGACGACTCAGGTAACATTGzATTACICTG-TAGCAGCATTAU-AAACACZ GC'T AACGCATA'GA -kACAJ 7tAAGGCTTTCCACAACGGTGGTATTGGTACAA ITTCTTTTCCAA-ATTI ATTGGTTTAAGCATTATGCT TGGAGCGGTAATITATCATGA mAAAGACGTCAATCAGAG.(GAAGC3rTTAA 40 ORF amino acid s xuuence (SEQ ID NO: 96: TDI SGY FGQGSKEI AOAFFAVN,-NESQTRY I TE SGTEVE SI DAAGVLKGLTTEJGIT TFNTANLKGTYQ I VELL DKSNYRNGDKV',LADSKAV? VKI TLLYNEEG1 IVDAEVYPKNTEEAFQI DRNFA, KANKLLNDSDNSAIAGGAC, DYDKYQAEKAK"ATAE10% 1 PE ,VI{TK1 ' QKGSRYKN~LAW VDTNSNIGLT 4GNTVNKLEAkSSG7SFVEGTDY'J~ER 45 DDROFTLKFTDTGLTKLOKEAETHAV EFTLTYSATVNGAA&I DDKPESNDI KLQYGNRPGEKVKET1 VTE'S1G S ITVSKTNDKGSDLEtNVVYTYLKDCGTrAVAzSVSLTKTTPNGE INLGNl KFTVTCAFAGCKFSGLTDSKTYM I SER IAGYGNT IT TGAGSAAXT TNTPDSDNTPFLNFTERV TG KE VKTS S TET FLQGAQVV7,KDSAG-KY LALKSSAT I SAQT TAYTNAK1TALD;AKIAAYNKLSADDQKGTKG-ETAKAE IKTADAT-YNAAFIAA TYEWW7 NKEDA.-,rTNVVTSNADGQFEVSLJATDYILETQAA.GYARLAGDV7DFKVG CNSSKADD)!S-NIlDYTASSNKKD 50 AQR1ENKKV,7TIPQTGGIGTILFTIIGLSIMLGAVIIMEKRRQrSEEA Strain 6313 GET DNA-sequence (SEQ ID NO: 139) ATGAA.S AATCACAA; ATGTCTTACAG TGTTCTC0A1-CACTCTA'TTGA^tTCTT;AC'GTCACTP2ITCTCAG'TT 55 GCACCA ,GCGTTTGCGGACGACG.TAACAACTG.ATACTGTGAC CTTGCA-CAA;,GATTG-TCATG;CCACAAGCTG (LCA, TTTGnTAAGTTTACTGAAGCTACA;AAGGTAACGAATGATAG-CGATTATGTT GG TAAACAA ATTAATGACCTT AATCTTATTTTGGCTCAAC'CGATGCTAAT AGA-A ATTAAGGGTGCTTTCTTTGTTTTCAAA AATGAAAVCTGGT ACAA^-rAATTCA TTACTG-aAATGGTAAGG AAGT-CGATACTTTGGAAGC-TAAAGATGCTGAAGCzGTGG(zTGC-TGTT CTTTCAGGGTTAACAAAAiGACACTGGTTTGCTTYTTAAOCTGCTIAGTTAAAAG2GAACTTACCAAZ ATCGTT 60 CAA TTGAAAGAAAAATCAAA,'CTACGATA.ACAACGGTTCTATCTTGGCTGATT-AAA.CAGTTCCAQTTAA ATCAGTCTGCCATTGGTAAA.CAt&CCASGTGTT GT TAAC-ATQGTCACATl TTATCCAAAGAATAcTGAA A'AACCACAAGTAGCATAAGA;ACT'TQCAGATAA AGA TCTTGATTATACTGAC-AACCGAPAAGACAAArGG'TGTT GTCTCAG-CGACA-,GTTG.STG AJAAA,A AGPA TACAT AGTTGGAAACAAAiATTCT TAAAtGGCTCAGAC TAT lutc AAA-7CTGGTTTGGACTGATAG CATGACT- AAGGTTTGCGTTA.BAr-ASCAACGTTAzAAGTAACATTGGA4TQGT 5 AAAGATTTTCCTC-TTTTAA ACTACiA CTCGTAACAGA',rGACCAAGGTTTCCGTCTTGC-CTTGAA!VTGCAIACA GGTCTTGCA14GCAGTAGC CAS;CTGCTGC. AAAA CKAAG(ATGTTGAAAT(ZAAGAkTCACTTACTCAGCTfACGQTC AACGGCTCCAC-TACTGTTGAAGT-TCCAGAAAGCAATGATGTTAATTGSACTATGGT5ATAAPCC^AACGGAAT, GA~rAAGTGAllACQACAAGAA^GGTACTCCAGCTAACCAPAGAa71ATTAAAGTCATTAAACTGGGCAGTArlTGGT ACAATTACTGATGTTAA.TGTTGCAGTTAAAGCTATCTTACCTTGCAAGAAAA CAAACGGATGGTACATGG 10 GTGzAACGTTGC-TTCACACGSAAGCA-ACAAA; ACCATCAC-GCTTTGAACATACTTTCACAGGTTTGC.TAATACT AAAACTTACCG-CG^TTGTCGozAACGTGTTASCGGCTAC-ACTCCAGAATATGTATCATT AAAAA.TGGTGTTQTG ACTATCAAGAACUrAACsAAAAA.CTCAAATG ATCC-. ACTCCA.ATCACCCATCAGtAC -CA-AAAGTGGTG'ACTTAT GG ACGTAA"ATTTGTGAAA ,ACAAaTCAAPGCTAACAC2'GAACGCTTGGCAGGC AGCTACCTTCCTTGTTA'AGtAA. GAAGAAAATACTTGSCA'CGTAAAGCAGGTGCAG CALC-'TGCTGAAGCAAA-GGCAGCTGTAA.MA3CTGCTA.A is CTA' GCATTGG ATGA AGCTGTTAAAGCTTAsTAACGAC TTGCTAAAGAAAACAAGAAGG'CCAAGAAG GTA ,A ACAG CAT TOGCTACTG TTGA-TClz\-AAAAQAAAAAjGCTTA,-ACAGCTTTTGTTAhAAQCTAACTACT CAT A! GAzATGGGTTSPCAGATAAAA--UGGCTGATAATGTTGTTAkAATTGATCTCTIAkCGCCGGT GGTCA.ATTTGA.2- T T ACTGGTTTGGAkTAGzAGCACTTATAGCTTGAAGPACTCAGCACCAGCCAGGTT TGC-GACATT-GTQ-AGG GATSGTAAAC T TTGA AG:TAAC TGC CA CATCATAT AGCAAAGGGCT ACA;'ACT GACAT CGCA TAGATAAAOUGA 20 TCTGT A;AAAAGATGCGCAACAAGTTC-AAAACAAAAAAGTAACCATCCCACA.;AACAGGTGST ATTGGThA ATTCTTTTQACAAkTTATTGGTTTAAGCATTATGCTTGGAG CAQTASTTGTCATGA AAAACGTCAAZTCA 'AG GAAGCTTAA OAF amine acid sequence (SEQ ID NO: 97) 25 ESYFOSTDAKE IKGAFFVFKNETGTKFI TANG ZVDTLEAKDnEGGAV.LSGLTKDTGFAFNTARLIIKGTYQVIV ELKEKSNYONNGS ILADSKAVP'VKI TLPLVNNQGVV1KDAH 'I YFKNTETKPQVD: NEADEOLD' TDNtRKDKFGV VSATVGDEKEY iVGTKI U<GSDYKKLV' iTPSMTEQLTFN4NNVKVTLDO:,KDFFVLNY LVTDDQGFRLALNAT 1) TI ENNK. 51DFT P NPSEFKVV TYORKFVEiTNQ ANTERLAOAT FVKKEGKYLARKAGA ATAEAKAA.VKTAE LA LDEAVKAYNDLTKEKEECQEGKTA'LATVDQKQEA, YNDArIKA NYSYE IVADKK ADt'fl .7LISNAGGQFEI TGLDKGTYSLEETQA PAGYA(%T LSGDVI NFEVTATSYSKGATTDI AYDKGS VKKDAQQVQNKKV/TI PQTGGIGT I IIFTI IGLSIMLGAVVVMKKRQSEEA 35 Strain BAA23 OARF DNA sequence (SEQ ID NO. 140): ATGAAAkAAATCAA ICAA %ATGTCTTAOAA.TGTTCTCGACACTGCTAkTTGOATCTTAACGTCA.CTATTCTCAG;TT GCACCASCGTTTGOSGAC-GAOGrCAAC-AAOTGATACTGzTGAGCTTGOACAAGAT KIGTCATGCC-ACAAOZCTGOA TT G-ATAAC-TTTAC.TG AAGGTACAAAAGGTA4AGAATG-AT?2GCGATTATGTTGG m AAACAPAATTAAT-GACCTT 40 AAATCTTATTTTGGCTCAACCGATGCTA.AkAAATCAAGGGTGCTTTCTTTGTTTTCAAA ATG AACTGCT ACAAAATTCATTACTGAAAlATGGTAWPGAAIGTCOATACTTTGGAA.GCTAAAGA TGOITGA-AGGTGvGTGCTGT CTTTOA(GGTT AAOMGAAOAAjTGGTTTTGTTTTTAOACTOTA.GTTAAAivGAA!VTTTAQAAA, VTOGTT GAzATTG 3AAAG DAAAAATCA.DAAOTACOATAATCAAC -GGTTCTATOTTGGCTG-'ATTCPAAADGCASTTC'-CAGOTlA,A ATOACTCTOOCATTGGTAA ACAACCAAGGTC-TTGTTAA2 'ATGOTC'ACATTTAT-CC'AAAGCAATA-CTGAAAOAC 45 A.AACC'ttCAAG TAGATAAGAAOtATTTGCAGATAA&Z.,GATCTTGATT.ATACTGACA'ACCGAAAAO.ViACA.AG-GTOTT GTCICAGCGACAiGTTGGTGACAA-AAAGAATAC'ATA2GTTGGAAC-AAAA;4TTCTTAATGGTAGA-TATAG AA AGSTTTGGAOTGATAGOATGACTAAA-,GTTTGACGTTAACJ CQAAGGTTA AAGTAACZATTGGATGGT GAAGATTT TCCTGTTWTA.ACTACAA.ACTCGTAAC-AGATGACCAAGGTTTCGTCTTGGGTTGAATGCAAC-A GGTQTTGCAGCAG.TAGCAGQAGC.TGOAAA'AGAOAAA'GATGTTGAAATCAAG ATCM2CTTACTOAGOTAOOGTG 50 AACGOTGCAOTAOTGTTGAAAITTCCAGAAGACAATGATGTTAM TTGGAC-TATGTAATAACI-jAGGAA, G.AAAOTGAA CACA24AAAGGTACTCCAGCTAAC^CAAGAAATTA2kAGTCATTAASACTGGGO-AGTAGATGGT ACAATTACTGATGCTA.ATGTTGCAGTTAAAGkCCTATCT-TTACCTTGCAAGAAA%-ACAAACGGATGTACATGG GTG AA CGTTGCTTCACAOr-GAA4GG-AA;CAAAACCATCACGCTTTGAACATAkCTTTOAC-AGGTTTGGATAA%-TGCT ,'AAAC-TTACC-GCGTTGTC-GAACGTGTTAGCGGCTAC-AC'TCCAGAATACrGTAITCATTTA.AAATGGTGTTGTG 55 ACTATC-AA.GMACAAAAACTOAAATGATOGAA.'CTOOAATCAAOCCA.TCAGAAG%.CAAAAGTGG CGAOTTAT GGACGT~zAATTTGTGrA~AAC AATCA AGCTA-AOACTGAAGTTGGCAGGAGCTOGTTCCTCGTTAAOzAIA GYAGC-iATACTTGGCAC:TGGAGTGC3AGTC. iTGAAGY.lCAA GCAGTGTA.VitACrTGCTAAAi CTAGCATTOOMAGAGO -TGTTAACTTAT ACGCTTGATAAGAAAA"ilCAGAAGGOCASAAGGTAAA P-AAGCATTOGCTA.JGTTGATCAAf AAACAAAAAGC-TTACAATGACGCTTTTGTTAAA2GCTAMCTACTOATAT 60 GAAhTGGTTG CAGA 'TA&AAGCTG;APTTTTG'TTAAATTS7ATCTCTAACGCCGGTS7TGTCAATTTGAA, ATT AC.GOl-~rATV,, (-(7CCTJAGGCTTGGA qGAAACTCAAr-2CACCAG-CAGG.TTAT GC-GACATT GTCAGGT 1GAT-GTAACTTTGA:GTAACTGCCAATCTTAGCAA,'GGGCTCAATGAACGCATTAT-AAC;CQ- G ITCTGTAMltAIAAGATGCCCA'ACM-AGTTCAAACAM AA?..AGTAtC-ATC-CACAACAG :GTGGTATrTGGLTACA ,ATTCTTTTCA'CAATTATTGGTTh JAGCATT TGCT'GGA-GC-AG TA'GTTA'TCATGAAV7ACGTCUIATCA GAG" 5GANSCTTAAk ORE amino acis eun SQI O 8 i4iKKIIFCLTFSTLLLILTSLr WA PAE*ADDATTDVW~LHEIVMrtPQAEDNFTEGTKG .NDSDYVG-KQINDL KSYFGSTDAKE ThGAEEPfl NETGTKFlTENGKEVDTLEARDAEOWS~iLSGLTKDNGOFVFNTA dM01 .TYQIV ELEEKSNYDNNGSI1LADSKAVEYK ITLPLVNNQGVVKDAK 1 YPKNTETKPQVDKNFADKDLDYTDNRKDKGV 10 VSATVGDKKEYIVGTKI LROSDYKKTA 'iTDSMTKQLTEN4NNVKVTLDGEDEPVLNYKLVJTDDQGERL 1 LNAT GLIIA'AAAAAKDRDV7EI-KITYSATVN,?,GSTTVEI PETNDVKLDYQNNPTEESEPQEGTPA.NQEJ KVIKDWA.VDG T ITDAINAViEAI FTLQEKQTDGTWVNV',ASN,'EATKPSRFEIHTFTGLDNA %KTYRVV' ERVSGYTPEYVSKNGVVI T 1KNNRNSNDPT P N PSE?KXrTYGRKF'KTNQNTERAGATLVKEGKYLAEAAATAEAAAV KTAN LALDEAVKtAYN9DLTKEKQEOQEG KTALATVDQKQAYN~tDAFlKFANTYSYENAVADRKADNl-PVKLI SNACOQEE I 5 TGLDKGTYGLEETQvAPAGYIA'TLSG3DVN4EVTATISY SKIATTDIAYDKGSVKDQQVQNKX r-tT IPOTGIT ILETI IGLE IMLGAVWIMKNRQSEEA Strain BAA611I ORE DNA sequence (SEQ ID NO: 141): 20 Ag idiACAzi'TCTA TGTTCAAGCTTACT'AGCCATTAT GCACCAGCGTTTGCGGACGACGC-AAOAA7,CTGATACTGTGACOTTGC-ACA.AGATWGTCATGCCACMAGCTGCA TTTGA.TAACTTTACTGAAGGTACAPAAAGGTAAGAATGSATAGCGATTATGTTGGTAAC?.AATTAATGACCTT AC ATCTTATTTTGGCTCAA CCGATGQCTAAAGAAAt.-CAA tGGGTGCTTTCTTTGTTTTCAAAAATGA) AACIGG T ACAA-AATTCATTACTGA, .AATGGTAAG (AO.'TCOATACTTTGzGAAGCTAAA--GATGCTGA?,AGGTGGTGCTGTT 25 CTTTC AGGGTTAACAAAAGACAATGVGTTTTGTTTTTAACACTGCTAAGTTAAA AGGAATTTACCAAAITCGTT GA.ATTGAG~r AAAA4-ATC.A%CTACG3AWAZACAAC(-GGTTCTATCTTGCTTQ4I''-AGCAGTTCC4GT'hAA, ATCACTCTGCC-ATTGGTAAAO .AACCAAGGTGTTGTITAAAGATGCTCAC.AT TTATCAUGAATACTOAAACA tAC CAC AAGTAGA IAAG AC TlTT G CAGAT~uVAGIVYC T TGAT TAT ACTGA C AA CGAAAAGACAAAG GTGI OT GTCTCAGCGACAGTTCGTGoACs-AAAAAGA.ATACATAGTTGGAACAAAAATTCTTAiA GGC-TCAGA-CTATAAG 30 AAlACTGGTTTGGACTGAiTAGCATGACT'AAGitQTTGA' CGTTCAA-PACAAtCGTTAAG, TAACAT TG-ATGGT GAAkGATTTTCCTGTTTTMACTACA,ACTCGTALAGM I ACCA ,AGGTTT(ACC CTGTGftAIGCAACA GGTCTTGCAGC-AGTAGrCAGCAGCTGCAAAAGACA, AGATGTTGAAATCAArGATCACTTACTCAGCTACGGTG AA-PCGGCTCCACTACTGTTGAAAVT TCCAGnAzACCAATGA TGTTAJiATTGGACTATGGTAATA ACCCAA.CGG A GAA',AG TGAAC CAC AAG AA G GTA CT -CAGC T AAC CAAGAAA T TAAAGT C AT TAAAGAC TG G GCA GTAGA TGG T 35 ACAATTACTGATGCTAATGT TGCAGTTA.A -cQTATCTTTACCTTG7AGZ,AXCICAAOGGATGYTACATGG GTGAACGTTGC-TTCACAC-GAAG CAACAAAkACCATCA ICGCTTTGIACATAkCTTTOACAGGTTTGGATAATOCT AA-T TA-C GCT T GT CGAAC GTG TTAG CG GCTACAC T CCAG-TACGT ATCAT TTA.AAT GGTGTT GT G AC TATCAGAAC-AAOAAAAAT AA TGATC CAA-T C CT ClAC CC AT CAGAACCAAAAG TG GT GAC T TAT GGACGTAAATTTGTGAA.ACAA 4ATCAG'CTA2kACACTGAACGC'-TT GG CAGC.AGCTACCGTTCCTC-GTTA.G(AA.T, 40 GAAGG3CAAATACTTGGC'AC-GTAAAGCAG-GTGCAGCAAiCTG'CTGAAGCAAAGGCAGCTGTAAAAA 1CTOCTA;A C TAG CAT T GAT GAAG' TG T TAGCT TATAC GAC TT GAC~GAAAA~AC AAGAAGGC;AAGAAGG TAAAL ACAGCATTGCITACT GTTGATCAZ,%ZAAAAAAAAA GCTTACAATGACGCTTTITGTTAAAGCTAACTACTCATAT GAAuzTGGG TTGC-AGAPTAAAAAGGCTGATA'ATGTTG TTAAAPTTGAPTCTC'XhACGCCGGTGGTCAAITTTGAAkATT ACTGGTTTCGAT AA GGCACTTATGGCTTGGAG&AA %CTCAAG CACCA'GC AGGTTATGCGACAtTTGTCAGGT 45 G.ATGTAAACTTTGAAGTAACTGCCACATCATATAGCAtAAGGGGCTACAAC-TGACATCGCATATCATA.2AGGC T C TG T??-JAGAAT GC CCAACAGT TACZ4%A3AA C~GVCTCA; CACAGG TGG TAT TGG TACA ATTCTTTTCAC"AATTATTGGTTTAAGCATTATGlTTGGACAGTAGTTATCATGAAAAPACGTCAATCACAG GAAGOT TA O'RE amino acid sequence (SEQ ID NO: 99): KSYEG7STDAKE IKGAFEEVEKNETGTKEI TENGKEVDTLEAKDAEGGAVLSGLT .DNIGFV NiTAKL{GI YQIV E LKERSNY DNUGS I LADSKFAVPVRI TLPLVTNNQGVV.KDAH I Y PRNT ETK PQVDKN FADRDLDYTDNRKDRGV VSATVJGDKEY IVOTKlLKGSDYKELVW~TDSMTEGLTE-NNNVKV,'TLDGEDFPVLNYKLV TDDQGERpLALNAT GLA-A-VAADKDX/E I I TYSATVWGS;TTJE I PETNJDVKLY NNPTEESE PORGY PANQEI I AlKORAVO, G 55 T ITDANVAVKAI E TLQEKQ)TDG TWVIIVASNEATKFSREiTETGLDNAKTYPrVVERVSGYTFEYVSEKNGIVV T IKtIN4KNSNDPTP INPSEKV-VTYGRK.FVKTNQAENTERLAGATELVKKEGRY LA-RKATGAA TAEAK;AVKTAK LALDEAkVRAYNDILTKERQE;GQEGRTAATVDKRAYNIDAVANYSYEWVl~AD-KADNVVRTJL ISNAGOEEI TGLDKGTYGLEETQAPAG 'ATLSGDVIEEVTATSYSKGATTDIAYDKGSKDQQVffQNKKIT I PQTGGIGT 60 E T - G ~ t L A V I K R E ----------------------------------------- ---- -84 Strain C388/10 ,r .. DNA sequence --(SEQI O 4~ ATGraAAAAATCAACAAATATTTTGOAG TCTTCTZGGOATTGCTAC-TGACCG2 AAOATCATTGTTCTCAGTT 5 G CATTTGAC^GGTT TTACTGCTGGTACAA GGGTAAGGATAATACTGA-TACGTT GTAA',CJATCGAAGAIC GGTAGCTAA.ATAGAz'TCACTGAAAAPTGGTGAA A.AGTTGATAC--TTGGATACAACA.GA'IGCCAAAGGTGGTGCT GTTC-TTM200TTTACAACAA-AATGTTTCAATTTAA(ACTTTAATTA CAGGAAC-TTAICCAATC G T TGAA TT G AAAG3;,kAA T CTA CA TACAA CAA CGA TGG TTC-TATC TT G GCTG AT-1CPAAAG CA GT TCCAGT T 10 AA.AATCACTCTTCCATTGGTAACG-r CA.TGGTGTTGTTAAAGACGCT-ACGTTTAT-CAAAGAACACTGA ACA,;AACCACAAGTA(3AT%A(AAACTTCGCAGATAA.AGAA.CTTGATTATGCGAA.CAACA.AAAA.AG5ACAAA %GG; AC'IGTCTCAGCATCTGTTGC-TGA.TGTTAA-;AAAkTATCATGTTGGAAlsCAAAAA-k~CCTTAAA-GGTTCAGACTAT A-AGAAkATTAA TCTGGACC'GATAGCATGACCAAAGGTTTGAC TTTCAACAACGATATTGCTGTAACAT T m GGAT GGTGCA ACTCTTGATGCTACA.AATTACAAAkCTTGTAGCAGATGACCnA.GGTT TCCGCCTTGTCTTGACTGAC 15 j AAGGTCTTGAAGCAGTGGC -AAAACCGCAAiAA"ACAAAATG TTGA AATCAAGATCAC-TTACTCAGC-TACT TTGAACG GT T CT GC TG T CG T TGGT T CTA G AC CAA TGA T GT TAPJT T GGAC TAC G GCAA(; AACC CAACA AT TG0AAAA.TCGAA CC A AAAGA AGG TA T TCCA G TT GATA4AMA.ATCA CTG TTAACAMAC AT GGGCA GTAGA T GGC'AATGAAiGTG AATz'AAAGCAGAPTGAAACAGTT4GATGCTGTCTTCACCTTGCAAGTTAAAGATGGTGACAAA T GGGT GPA T G TT GA TT CAGCTAM VG C1'AC.,5CT GCAAC TAGCCT T CM1AACACA CT T TTGAAAA CTInTG GA T AAT 20 GCTAAA7ACTTAICCCGTTATCG AACGTGTTAGCGGCTACGCTCCAGAATACGTCTCATTTGTA AATGGCGTT GTSADO CCA C .ACA.AAGWA C T .AAA-T GAG C CAAC T CCART CAkC C CA TCAGMAAUAAG TG GTGAC T TATGGACGTAAATTTGTGAAAZ ACAAATA&AOATGGkm"AAAACGCTTGGCAGGAGCTACC-TTOCTTCTTAAG, Ar-AGATGGCAAGTACTTGGC-ACGTAAA.TCAGGT.GTTGCAAC-AGAT.GC.AGPAAAGCTGSCTGTAGATTCAtACI AA ATCAGCATTCGATGCTGC,-TGTTA.AAGCTTACAATG ATTT ACTAA GAAAACAAGIAGGTCAAGATGGT 25 AA ATCAS.CATTGGCTACCGTTAGS GAAAAACAAAAGCT TACA-ATGATGCCTTTGTTAA AGCTAACTACT-CA TACfGAATGGGTTGAAGATAAAATGC-TAAGAATGTTGTTA.AATTGT' TTCTAACGATAAAGGTCAATTTGAA ATTATCTGQCTTGAkCTGAAGQTCATACTCATTGAAGAACAAA~GCA-CCALACTGGT TATGCTA.AATTATCA GGTG ATGTTTCGTTTAATGTTA.A.TGCTACTTCATACAGT AA&GGTTCTGCTCAAG(ATATTGAGTA,;TACCCAA, 1GGTTCTAAAACTAAA!;GATGCACAACAAGTTA-TCAATAAGAAGGTTACTATTCCAC AA~CAGGTGGTATTGT 3 0 P AAATTTTTTTC-AC-AATTATTG GATTAAGTATTATGCT-TGGAGCGGT ACTTATCATG ATIAAGACGTCAAT CA IGAGCAACTTTAAz OR' amino ac: d sequence (SEQ IED NO- 100): MKK IN1YFAVE7SA LLLTVTSILFSV' APVTFAEEAKITTTVTL{KIV%IPR-TAFDGFTAzGTKGKDNTD-?VGQ ED-r. L T)YGCSGEA KE lAGA,'YFAFEEACTEY I TEN7GEEV.DTLD:TTDA.KCGAVLIKGLTTDNG-FK -FNTS-KLTGTYQI 3 E EKSTYNiNDGS I LADSKAVPEVKJ TMIJVN,1DNGVV'.KDAIRVYPKNTETKPQVDKNFA.DKELDYANNKKDRG T" VSASVO DV7KK YWVGTKI LE-GS DYrKELI WTDSMTKGLTFN-lNDIAV',TLDOATLDATNYKLVA, DDQGFRL-VLTD) KG ~AVAAAEKDVE11 TYATLOSAVEVLTNDKLDYNNP I NE2EGI PVDKKITVNKTWkVD ONE 'MADETVDAV7FTLQVEFGDKWVNiVDSAK4ATAATSFKHfTFENILDMATYR VI ERVSGYAPEYVS FVNGV VT INNt KDSNt4EPTP21 NFSEPIJKVVTYGRKFVYTNKDGKERLAGA TFLVKKDGKYLARKSGVAPTDAIEKAAVDST 40 FCSAL DAAVKA, YNDLTKERQEGQDGKSALATVS-EKQKAYN4DAFVK-ANY S YEWVIEDKNAKNVVKL 1 SNDKGQFE 1-TGLTEGQYSLE FETQAPTGYIAKLSGDVSFINNATSY- KGSAQDIEYTOGSKTKDQQVINKVT PQTGGIG : IFFT1 IGJSIMLGAVV1MKRRQSEEV Strain AG97 45 1 R' DNAq sequence (SEQ ID NO:0 143) ATGAAG ATCAAAAATATTTTGAATGTTCTC-GCAT GTTATTAATTT'AC ATCGTTGTATCGGTA, tiC CCGGTATTTGCTGCTAATGGM,,iATTCACTAAK ,CAG,-TAC.CTTACACAJTTG TTCAAA CATCC GAi AATTTGG CTAAGCO-AA2ATTTCCC-AGOAARTAAATGGACTTGAA.TGGAA2CGAAGTATAtTGGGTC.AAAAAOATT :, CACATTTCALGATATTTTOGGCA AGGTTCTA-AG-AAAZTCGCC.GGTOCTTTC-TTTGCOGTTATGAATGAA 5r0 AGTCAGPAAAATATATCACAGAAAGTGGTAC-TGAAGTAGn.AAGT.ATCGA~sTGCAGzCAGGTGTC-CTTAAACGT ITTG ACAA,-CG'AAACGOCATTACATTTAATAC ±GC.AAACTTA'AGGAACrA-;(- TACCAA2ATCOTTGAGTTGCTT GAC.AAA %TCTA.ATTATAAAAATGGTGACAAAOT-TCTTG CTGACTCAAAAGCTG-TCCCAGTG PQATCAr-TCTT COTTTG TATPACGAAGPGG.ATGTCGTGACGCTA3.GTGTACCA-AGAATACAGAAGAAG-ACCACAAk kT,,CGACAAAAC-TTTGCTrAACAAATAAATTGTT4GAAT4GACAGTGATAATTCAGCTATTGCAOGTOOGGC-A 55 OACTACGAC.AAATATCAGGO-AGAA.kUAGCAA, AGCTACTGOTONkAATCGQTCAAQAA ATOCCTTACGAA GTT AAAACAIaAAATCCAAAAzuAGSGT4CTAAA sTACAAAA,3 ACC TTGCTTGGG3TCGATACC-ATGTCA-A ATGGTTTGACA ATOGGTAACACTGTTAACl^TTAGAAGC7,^TCGrTCAGOCWC' TTTOTAG AGGTACAGAJTACAPATGTTGAAe'CGT GA TGACCGTGGTTTCACTT'GA-AATTCA'-AGATACAGGTTTG'CT-ACTCA.AAGC7AGCGAAAuCAOAAP GCTG'TOAATTC-ACATTGACATAT AOCG.AACAGT-TAACGGTGCOGCTATTGATGACA-AGCCAGAAAI GCAA.T 60 GAT'AT-CAACTTCAATACGGTAA,%CAAA. CCAGGTAAAAAA~zGTAAAAGAAATCCCAGTAAtCACCGTCAkAATGGC -85 CIAAATCAkCTGTTAQCAAAATTCGGCAAAAGGTTO,.AOATTTAGAGAATGCGAAkTGT-TGTTTATkCCCTTAAA; GATGGTGGAzACAOCTGTTGCCTCAG TTTCAzT-TGACAAAA CAACACCAA-ZATGGCGA4AATCAACTTAGGTAA %T GGTATTAAAiTTTAC-AGTTAC"TG-GGTTTG CTGG TAAATTCAGTOGGTCTGACTGATAGTAAAACATAC.ATG ATCTCAGAACOTATGGCTGGTTAx TGGTAkATACAATCnCTACTGTCTGGTAGTGCAGCTTCACCATAkCT 5 CCAGATTCAGAO AA-CC;ACACCACTTAATCCAACTGACCAAAGTTGTGACACACGGTAAAAATTCGTC kACAAGT TCGCTAALACAGACGCTTGCAGGTGCACAGTTCGTTGTTAAVGATTCAGCTGGTAAAT ::AC CTTGCATTGkATCATCTGCGACATATCAGCTCA.7-ACAGCTTAACAAATCTV.AACTGCTCTTGAC GCTAPJSaTCGCAG.CTTAl CAAC-AAA;CTTTCA.CAGACC-ATCAAAAAOGTACTAAAGO.-TGAAACAOCTAAAGCA OAAATCAAAkACTGCTCAAGACGOTTAOAA.TQCAGCCTTOATCGTAOCTCGTACAGCTTACGAG:GGGIAAC~(.T 10 AAZTAAAGAAGATGCTAACGTTGTTAA'AGTGACTTOAAAGCGCTGACGGTCAATTTGA2"tGTTAGCGGTCTTGCA A AAGTTGGAIAACAzIGCTCAAAA;GCAPGA2CGACTCAGGTAA.2CATTGATTACACTG CTAO-;AGCAATAAA.AAGA.C GCTCAAlCGCATAG2~AAA.CAAAAA AGTC-ACTATTCC-ACAAAPCAGGTGGTATTGGTACAATTCTTTTCACrAATT A6TTOGTTTAAGOCATTATGOTTGGA2GC{GGAATTATCATGAnAIAGACGTCAAkTOAGAGGAAO3.CTTAAk N tAXI KYrAMrSALLLl LTSLLSVAPVFAAEMGN ITKTVTLHKIVQ7rTSDNLAK-PNFPGI NGLtIGTKYMG QRL TDI SGYFGQGSE I AGAFFAVMi NESQTKYX TE SGTEVE S I DAAGVLKGLTTENG I TFNTANLEGTYQ I VEL L DKSNYKNG'DEVLADSYAV'?,FVITLLYNtEEGIVVFD?2.VYPRNTEEAPQI DENFAKAN'KLLNDSDNSA1IAGGA DYDKYQA EK-AKATAETICQE IPYEVKT 4 QKQSKYKNLAWDTMSNG-LTMGNTVN LEASSOSFVEOTDYNV EP 20 DDRG-FTDKFT DTGLTKLQKEAETQAVIEFTLTYSATNlG,AI DDKPESNDTKLOYGNKPGXR VEIlPVTPSNG E ITVSKTWDKGSDLENANVVYTLKDGGTAVAz'SVS LTKTTPNGE IIL3NG IKFTVTGAFAGKFSGLTDSKTYM I SERI AGYGN T ITTGAGSAA I TNT PDSDNPT PLN PTE PKVV7THGKKFVKTS STET ERLQYAQFVVKDSAGKlY LALKS SAT I SAQTTA YTNAKTALDAKIAAYNKLSADDQKGTKGETAKAE XKFTAQDAYNAAFIVA.RTYEWvrT NKEDA NVV,7KVTSqNADO-QFEV SGLA, TGDYKEEETQAPAG'C4YA I.AG ,VDFKVGFrNSSKADDSGN4I DYTASSNKKD 25 AQRENKKV?1 PQTGGIGTILFTI IGS1MLGAV/1MRRQSEEA strain !C98 ORF DNA sequence (SEQ ID NO. 144), ATGAAAAAA.ATCAACAAAkTGTCTTACAlATGTTCTOGACACT GCTATTCA1 TCTTAACG.TCACTATTC'TCAG TT 30 GCACCAGC-GTTTGCGGA.CGAC-GCAA CAA14CTGATAC-TGTGAjCCTTGCAO.AAGATTGTCATGCCACAAOCTOOA TTTGATA.ACTTTACTGAAGG2TACAAAAGGTAAG-AATGAT4AGCGAPTTA TGTTGGTA AACAA-ATTAATGAC CTT AAATCTTATT TTGGCTCA-ACCGATGCTAAAQAAA; TCAAQGGTQ'CTTTCTTTGTTTTCXVAAATGAA3ACTGGT A"CAAAAT T CAT TAC TGAAAAT GGTA.AGGAATGT CGATAC T T TGGAAG CTAAAGAT GCOTGAAGT GG TGC TGT T CT T TCAGG G TTA.ACAAAAGACAATGTTT TGT T TT IAACACT G CTAAG T TAAAAGGAATT T ACCAA TOCOGT T 35 GAATTGAAAGAAAAAT CAAACTACOATAACAACOGGTTC TAT CTTGGCTGAT TCA.kAAAGCACT TCCAGTTAAA AlTCArCTGOCATTOOS'AArACAACCAAGGTG TTGTTAAAGATGVCTC-AATTTATCCAAAGAATACTA4.2aO(A Aa C CACAAG TAGIAT .AGAAC TT T G3AGATAAAVGAT CT T GP.T TATAC TGACAMA,7AAAC-ACAAAGGT GT T OTCTCAGOGACAGTTOGTGACXA7-AAAGAA ,TAzCATAGTTGGAACAAAkAATTO-TTAAAUGGOTCAGACTATPAG AAAj'CTQGTTTGGAOTGATAGCATGACTAAAPGGTTTOACGTTCAACAACAACGTTArAGTAACsrATTGGATGGT 40 GAAGATTTTOCTGTTTITAADACTACAAkACTCGT3AO-AGATGACClAAGGTTTCCGTCTTGCCTTGATGCAACA GGTCTTGCAGCAGTACCAGCAGOITGCAAAAGAO-AAAG CATGTTG~z-AATOAAGATCAOTT ACTCAGCTACGGTG AAOftGGCTCCACTACTGTTGAAATTCCAGAA %ACCA ATGATGTTAAATTGG ACTATGGTAATAACOCAA CGGAA GXA.iGTGAACCACAAGz.AGGTAOTCCAGC-TAACGAAGA.ATLTA.AAGTCATTAAAOACTGGGOA'GTA"GAT GGT AC -AATTACTGA TGC TAATGTTGCAGTTAAA; GCTATCTTTACCTTGAAGA-kAACAACGG ATGGTACATGG 45 GTG3AACSTTOCTTOADCACGAAGCAA CAAAArCATCACGCTT TGYAAATACTTTCACAGGTiTGATAAPTGCT ,AAA.CTTACCGCGTTGTCGAACt3TGTTAGCGGCTACACTCCAGAATA CGTATCA'TTTAAAAAT(V-WGTCTTGTG AC TA TOA AQ1C0%AATCAAAT GAT C',AQT CCA ATCAAC CCA T C AAACOCAAAAG T G G TGAC T TAT GGACGT?,AATTTGTG:-AAACAAATTCAAtGCTAAkCACTGAA %CGCTTGGCAGOAGCTACkrCTTCCTCGTTASGAAA QA-k GOQiVATAOCT2GGC. CGTAAA GCAGGVTGCAGCAACTGCTGAA JGCAAAGGCAGCTGTAAAAGTGCTAAA. 50 C TAGCAT T G ATGAAGC TGT TAAA.GC TTA TAAC-GsAC T TACAAAAAAGkGCAAGiAGGTAA-A A CAGCATTGGCTACTC-TTGATCAAAAACAAA2-AAGC-TTACAzATGACGCTTWTGTTAAAGCTAAOTAOTCATAT GOAAPTGGGTTGCAGATAM V.AGCTGATAA-TQTTGTTAAAzTTGATCTCTAACGCCGGTGGTCAA, TTTGAAATT ACTGGTTTGGAT.AAGGCACTATG3CTTMSAkhGAACTCA4GCACCAG-CAkCYGTTATGCGACATTGTCAGGT IGATGTAPACTTTGPAGr TAA.CTGCC-ACATC-ATATAOCMAA%GGGCTACAACTGAC-ATCG CTATG TAAG 55 1 TCTGTA.ZAAAA.AGATGCCC-AAOAAGTTCAAAC~A)-AAAATAACCATCCCACAAcpAGGTGGTA TTGGTACA 7 TTCTTTTCACAATTATTGGTTTAAOCATTATGCTTOGrAGC-AG TAGTTT. G-,diP(';C C , GAAGQTTAA ORF aMilno acid aecluencpa (SZQ 10D NO, 102) MKKINKCLTNFSTLLLI LTSLFSVA, PA FADDATTDTVTLIK IVNPQ AAF'DN FTEOTI GKNDSDY TGODIN DL 60 1 SYFGSTDAKE I KGAFFVFKNETGTKF1 TENG KEVDTLEAKDAEGAVLSGLTKDNGFVFKNTAKLEGIY~QtV -86 ELKEKSWYDNt4GS ILADSKAVPVKITLPLNNQVVK/DAIizYPKNRTETKPQVDKN-ADXDLDYTDNR kyDKGV VSATVGDK'SY IVG3TnK? GSDY J.JVWTPSMTKGLTFnNNVN- ,7VTLh-DGEPVLNYeKLVTDDQG NRLAL 4 NIAT GLAAVAAAAKDKDVEIK I TYSATV,.NGSTTVE I FETNDVfKLDYGNNFT EESE FQEGTFANQEI KVIKDWA-VDG TI TWA WTAVKAI FTLQEKQTDGT ,Pi:VVASHEAT .FSRF'EHTFTLDNAXTYR-VVERVSGYT FEY VSFKNG VV 5 TI KNNKNSNOFTPINPSEPKWTYGRFVKTNQANTERLAGATFLVKEGKYLARKAAATAAAAlKTAK LALD-EAVK FAYNDLTKEKQEGQEGK TALATVEQKQKAYND-APQNANl~YSYEWV',ADKKADNW% ,KLI SWAGGQFE I TOLDi{GTYGL;EETQAPAGYATLSGDV;NFEVTATSYSKGYATTDIrYDGSVKKDAiiQQVQNKKVJTI POTOG7i GT ILEITI 1GLSINILGAW lINKKjQSEEA J0 Strain 1C105 ORE'DNA equnce SEQID N: 15): ATGAAAAG AATC-AACAAATATTTTG3CAATGTTCT-CGG;CATTGTTATTAnATTT:TAACATCGCTTGT-TATCGGCTA GCTCO-GGTATTTGCTGCS'GCAOAPTGGGAAATATCAC-TA,7-ACAGTAACCTTA'CAAAAT GTTCAAAZCATCC GATAATTTGGCTAA%-GCCAkAATTTCCCAGGAATAAkATGGYATTGAA TGGAAkCGAAG7TATATG'GGTCAAA3AACTT 15 ACTGACATTTC-AGG ATATTTTGGOCAAGOTTCTAUPiAGAATCGCCGGTOCTTTCITTTGCQGTMTATGA ATGAA AG TCAGACAAAkTATATCACAGAAPAGTGGTAC-TGAAGTAG-AAAtlGTATCG TGCACAGGTGTCCTTAAGGT TTGACAACTGALArAnGGGCATTACAITT.AATAC TGCAJ,CTT ,AA;,CGAtCATACCAA ATCGT TGAGTTGCTT QACAAA TCTAATTATAA.AA'ATGGTGAOAAAO&.TTCTTOOTGAC TCAAAAGCTOTOCCCAGTOAAkAATCAzCTCTT CCTTTGTATA ACQ' AAAGGPTTTCGTGGACGCTGAATGTATCCAAGAATACGAA AAGCACCACAA2 20 ATCGACA.AACTTTCTA.A.,,GCAATAAETTGTTGATGCAGTGATATTCACTATTGCAGGTGGGGCA GACTACGAPCAAA')TATCAGOCAGAAAAAGCAAAAGC'TACTGCTGAAATCOGTC-AAGAAATCCCTTACOAAGTT AAA ACAAAAiATCC"-AJAJAGGG TC TAAATtAAACAAC CT T GC TTGG GT CGATAC CAT GT CA AT GG TT T GACA ATGGGTAACACTGTTAAkCTTAGAAGCATCGTCnGGCTCTTTTGTAGAGTACAGATTAAATGTT3A.ACGT C-ATG7ACCGTGGTTTCAC--TTTOPAATTACAGAAPCAGGTTT ACTAACTACP-AkAGAAGCGGAAPACACAC 25 GCTGTTGAATTCACATTGACATnTAGCGCAACAGTTAACG3TGC'GGCTAT TGATGACAA.GCCAGAAA GCAA.T rZATATCAACTTCAATACGGTACAACCGGT.-;AGTAAAGAAATCCCAGTAQACCTCAA4TGGC GAA7ATCACTGTTAGCAkAAACTTGGGACAAAO%.GTTCAG ATTTAGAGAATGCGAATGTTGTTTATACCCTTiAA GATGGTGGAACAGCTCGTTG0CTCAGTTTCATTGACAAAA,-ACAAkCAQ^CAATGGQG AAATCYACTTAGGTAA T C-GTATTAAATTTACAGTTACTCGACCGTTTOCTCGGTAA ATTCACTOGTCTGAC-T(7TAGTP-AAA7-'ATACATO 30 A3TCTCAGAAC~-'GTATCGCTGGTTnTGTA4ATnGAAT-CACTACTGGTG CTGGTAGTGCAGCTATCAkCAAkTACT C CAGAT T CAGACAAC CCAAOACCA'T T AATCA'C T GAACA.AA-G T TGT GACACAO G G T AAAAATT C T C AAA ACAACT TQGAC TGAAACAGAA40GCT TGC AAGGT GCACAQT TCG TT GT TP%AfAAT TCAGCT17GG TAAATAC CTTGCATTGAA.ATCATCTGCG;ACA.TJATCAGCTCAA'iACAA, CAGCTTACACMA5;TGCTXAAPACTGCTCTTGAC GC TAAAOAT C GCAG C TTAC AACAAAC T T T CSC AGAC GATQAAAAAOGGTA r-TAPAGG TGAAACAGC TAAAGCA.' 35 GAkAATCA.AA ACTCGCTCAAkGACGCTTACAATGCAGCCTTCATCGTAGCTCGTACOCTTACGOTGGTA-ACT A ATAAAGAAGATGCTAACGTTGTTA.AOTGACTTCAAAG GCTGACGGTCAATTTGAAGTTAGCGGTCTTGCA ACTGGTGATiTATt'AAACTTG7 flJGPACACAO.CTCCG,,-CTGGTTACGCTA.ATTAG7CAGGTGATGTTGATTTC AA.AsGTTGGA-AACAGCTO-AAAkAGCAGACGACTCAGOWAAOCATTGATTAC'ACTGOTAGCACA CATAAAAAAG AC C-CTCACGCATAGAAAAAAAlAAGTGACTATTCCACAAACAGGTGGTATTGGTAzCAATTCTTTTCACAADTT 40 ATTGOTTT.AAGOATTATGCTTGGA' ACGGTATTATcATGAAkAAGACGTCA-r-cACGAGmGkCTTAA ORF amino acid sequence (SEQ ID NO: 1031 MKRINI<YFA'MFSAlt LLILTSLLSVMWArA7EMGNI 'TRTV TLHKI VQTSONILAKFNFPG lNGLNGTKYMGQK)L TOI GYFQGSE IGAFAVNESQKY ITESOTEVES I DAA-GVLKGLTTENGI TFN4TANLKGTYCJ1VELL DKSN YKNODKV~tLAOS'KVF T'VKI TLILYNEEOIlVVDTEAEVYI(NTEEAFQIDKFKMKLNSNSAG 45 DYDKYQAERAKA'TAE; IGQEI FYEVKTI 1QKGSKYK<NLAW~IVOTMS.NGLTMiGNT-4VNLEASSGS,FEGTDYNVER DDRkGFTLKFTOTGLTKLQKEAETHIAVEFTLTYSATV ,h3AAI DONFESNDOI XLQYGNKPGKKVREI PVTFSNG E ITVSKTWOI{GSOLEN4AN\ 'YTLKDSGGTAV, ASVSLTKTTPNSEI NLONGI -KFTVTGAFAGKFSGLTDSKTYM I SERIAGYGNTITTGAGSAAI-,TNTPDSDNPT [LNPTE PKVVTEGKKFVKTSSTETER.IQGAQFVKDSAG-KY LALESSA-T I SAQTTAYTNAKTALDA< IAAYNKLSADOQNGTXOGETAK-.AEKTAQAYNAAFVARTAYEWVT 50 IIKEDANVVRVKTSNAOGQ,'FEVSGIAATGOYKLFETQAFAGYAKLAQOVDFKVGA4SSKAOODSGNIDYTASSNKKD AQRIENKKV TIPQTGGIGTILFTIIIG dSTNLGAVI 77TMKRRQSEEA Strain 1C216 ORE ONA sequence (SEQ I0 NO: 146): 55 ATGAA%AAAAATCAACAUTGTCTTACAATGTTCTCGACAC,,-TG'CTATTG,-ATCTTAACGT'CACTATTCTCAG TT GCACAGPCGTTTGCGGACGzACGC-AACAACTGATA- CTGTGzAOGTTGCACAA %GATTGTCATGCQACAA' GOTGCA TTTGATAACTTTAOTGAAG-GTA CA-AAAGGTAAGAATGATAGCG3ATTATGTTGGT.AAAPCAAATTAA3%TOACC('TT AA.ATOTTATTTTGGCTCAAACCATG^OThAAGAAA'TQAAGGTGCtTCT'TTTGTTTT.CAAAAATGAAACkrTGGT A CAAArATTC-ATTACTGAAA.ATGG TAAGGAAGTCSATACTTTGGiAGOCTAAOATIGCTGA7,AGGTG(3TGCTGTT 60 C-TTTCAQ.GGTTAAiCtAAAOACAATS G'TTTTTTTAACACTGCTAAGTTA\AAGGAATTTACCAAAsTO-GTT -87 GAAi TTGLAAGP-A;ATCA-ACTACGTAC-AACGGTT-TAT-TTCT GATT C2AA-CC.GTTCCGTT^7A A TCACTCTGCCA'TTGGTAAA %C.AACCAAiGGTGTTGTTJAA7ATGCTCACTTTATCCAAAAi~ATACTGAAACA AACCACA.%GTAGTA-GAA %CTTTGCAATA.A4AGATCTTGATTATCTGACACCGAAAGACAAAkGGTGTT GTCTCAGCGACAGTTGCTGA CAALVAAG~'ATkATAG TTGTAA CAIAAATTCTTAAGGCTCCA ICTATAA; 5 AA-ACTGGW-TTGGACTGATAGCATGACTAAGGTTTGACGTTC!AACAACAACGTTAAAGTAA4CATTGGATGGT G.UAGATTTTCC-TGTTTT AACTACA-ACCGTAACAGA TGACCAAGGTTTCCGTCTTGCC-TTGAATGC'AACA GGTCTTGCAGCAG-TAGCAG CAG3CTG-ZCAAAGCACAAAGtATGTTGAAATCAA' ,'GATC-ACTTACTCAG-CTACGGTG A.ACGGCTCCACTACTGTTGAAA .TTCCAGAAACCAATG&ATQTTAA3ATTGGACTATGGTAATAACCCACGGA GA.AAGTG~aACCACAA GAAGGTAC TCCAGCTAAVCCAAGAAAT TAAGTCATTAAGACTGGGAGTAkGATGGT 10) ACAATTACTGA.TGCTAkATGTTGCAG,-TTMkAGCTATCTTTACCTTGCAAGAAAACAJJXCGGATGGTAkCATGa GT GACGTTGCTTCACAC-GTGCACAAACCATCAC'CTT TGAACATACT TT CAC AGGTTTGGATAATGc T AAAAi~CTTACCGCGTTGTCGA47ACGTGT'.TAGCGGCTACAil.CTCCAGAATACGTATCATTTAAAATGGTGT

T

XGTG ACTATCAAGAkACACAAAAA',CTCAA21ATGATCCAAG CTCCAATCAIACCGATC-AGAACCAAA2 AGTGGTGACTTAT GGACG7TAA-T T TG T GMAVACAA AT CAAG CTAACACT GAAC GQ-T T GQCAG GAGC TACC TTCC T C GTTAAGAAA 1.5 GAAGGCAAkATACTTGGCACGTAAPAGCAGGTGCAG CAAICTGCTGAAGCAA AGGCAGO-TGT?AV4C'- -TGCTAAAs C-TAGCATTGGATGA AGCTGTTAAz AGCTTATAAC-GAC TTGACTAAGAAAACAPGAAGGCCAAGAAQiAGTAAA, ACAGCATTG GCTACTGTTGA;,TCAkACAA; &kGCTTACAATGACGCTTTTGTTAAAG(CTAACTACTCATAT GAkATGGGTTGCAG-4AT2AAA-AGGCTGATAATGTTGTTA-A~ATTGATCT CTAACrGCCGGTGGTCAATTTGzAAATT ACTGGTTTGGATA,%AGGCACTTATGGCTTGGAAGAAC. TCAAGCAQCAGCAGGTTATGCGACATTGTCAGGT 20 GATGTAACTT TGA3%AGTAACTGCCACATCATATAGCA)%AAGGGGCTACAA.CTGACATCGCATATGATAAAGGG TCTGTA5,-A.'AGATGCCAACAAGTTCAA'-ACAAAAAGTAACATCC-CzCAAzCAGGGTATTG GTACA AkTTQTTTTC'ACAAPTTATTGGTTTAGl CATTJGCTGGAGCAGTGTTATCATG7A)AAACGTCATCAGAG3 GAAGCTTAA QRF amino acid sev:,ence (SEQ ID N10- 104) iKSYFGSTDiAKEI KGAFFVFKNETGTRFI TENGKEVDT1;EMRDAEGGAVL 1SGLTKD4GFVFN~tTAKLKG IYQIV ELI<EKSNYDNNGS I LADSFAVJPVITLPLVN*,NQGVVIKDAHI YPENTETKFQVDKNFAE{DLDYTDNRKD{QV5 VSATV'GDKKEYIVVTKI LKGSDYKKLVI,'TDS$TKGLTrtrNNVKVnTLDGiEDFPVLNYKLVTDOQGFRLIALNAT GLi2APKDKDVEKITYSATGSTTET NDV~KLDYGNNPTEESEQEGTPANQEIVI1DWAVDG 1 -IKNIIKNSHDPTPINPSEKW17 TYGRK/KTQATERLAGATFLVKEGKYLAR2rAGATAAKAAVK ,,TA ILA LDEA-VKA-YNDLT K EKQE G QE GKTA LAT VDQKQRA~Y N DA FVKAN Y SYE WADKKADNVK L SNAGG QFE I I TGLDKGTIYGLESTQAI'AGYATLSGDVNFEVTA ,ISYSKGA.TTDIAYDGSVKAQ.(,QVQNKKV-iT IPQTGGIGT 5 LFTJ IGLSIMLGAV'IMKKRQSEEA 1Strain IC245 GCACCAGCGTTTGCGGA' CGACGCA,1CACATGATACT-'GTGACCTTGCACAAGAsTTGTCATGCCACAAGCTGCA 410 T TT GAAAC TT TAC TGMAGG TACAAAAG GTA.AGAAT GAT AGC GAT TAT G T TGG TAAA-CAAAiTTAAT GAQ T T .AAATCTTATTTTGGCTCAACCGA71TGC-TAAAGC.AAATCAAGGGTGCTTTCTTTGTTTTCAAMA~TGAAACTGGT AC-AAATTCATTAC TGAAA ATGGTAAOGAAG TCGATACTTTOGAAGCTAAPAGATC-CTG-AAGVGTG'GTGCTGTT CT TCAG GGTTAA,%CPAAAGkACAATGGTTTTYT TTTTA-;fACQTGC TAAGTTA.AAAGGA AT TTACCAAATCGTT GAATTGAAAGAAT5AAAMCAA ACTACGATAACAACGGTTCTATCTTGzGC TGAT TCAU.AAGCAGzTTCCAGTTAAA 45 ATCACTCTGCCATTGGTAA %ACAA CCAA GGTGTTG2TAAA. GATGCTCACATTTATCCAAAGAA TACTGAAACA .AAACCACAAG~rTAG'ATAAGA.ACTTTGCAGr-ATAAkAGATCTTGATTA;T ACTGACAACCGA.LAAGA.CAAAGGTG'.TT GTCTCAG CGACAGTTGGT GACA-2-AtAGAATACATAVTTGAPACAAAP-ATTC4TAAGGCTCAA, CTATAAGv AACTGGTT GGACTGAT AGCATGACTAAAGG TTACGTTCACAACACGT TAA0%GTAACATTGGATGGT GAAGATTTTCCTGTTT TAAACTACAAACTCGAAC..AT GACC0AAGGTTTCCGTCT TGCCTTGAATGCAACA 50 GGT CTT GQCA G CA GT AQGfA QCAGC T G CAAAA GACA AA G ATG;T TQGAAA TCAA-G A TC A CT TA CT C A GCTACGG.T G AACGGCTCCACTAkCTGTTGAAATTCCAGA.AACCAATGATGTTAAZATTGGA.CTATGGAIIATAACCCAAkCGGAA GAA-AGTG AACCACAAGA-ACCTACTC CAGCTAACCAAG;AATTAAAG TCATTAA-AGACTGGGCAG TAGATGGT AQCAl!T TAC TGAT GC TAATG T TGCAGT TAAACTAT C TTTAC C TT GCAGAAC GAT GG TACATG G GTGAAXCGTTQCTTCACACGAA %GC-AACAAAAC CATCACGCTTTGAACATACTTTCACAGGTTTGGATAATGCT 55 A?-LACTTACCGCGTTGTCGAACGTGTTAGQGGCTACAQTCCAGAlATAC'GTATCATTTAAAAATGGTGTTGTG AC-TATCAAG AA %CAAC-AAAPAAC'TC.AAATG ATCCAACTCCA-AT-CAACCCATC'AGAACCA.A.AGTGG5TGAC;kTTATI GGAO-GTPAAATTTGTGAAACAAATCAACC-TAACACTCAACGCTTGGCACGAGCTACCTTCC-TCGTTAAGA-A GAZiSGCPAAATACTTGGCA CGTAAGCAGG TC-CAGC--A.ACTGCTGAAG CAAAl GGCAGCT4GTA-A.AACTGCTAAA CTACkCATTGQATGA-GCTGTTAMQACTTATAQGACTTGACTJ'.A AAACAGAGGCAAAAAGGVCCTAAAl 60 ACAGCA TTGGCTA CTGTTGATCA);-AACA-AAAGCTTACA ATGVACGCTTTTGTTAAAGCTAACTACTGCAAT OA ATQGGTTSCAG AT AA- AAGC TGATA-ATGTTG7T TAAA'-rTGATCTC'TAACGCCGGQTC'AATTXTSAAA'-T AcTGGTTTGG ATkAAG~CACTTATGGCTTGGAAGAAACTcAAGC~ACic,CAGGTTATC~cACATTGTcAG(;T GATGTAAA.CTT TGAAO TAt&TSCCACATCATATAGCAAA7GGGGC-TACAAtCTGACATC&Z'-ATATSATAAAGGC TCTGT7.As)'AAGA-TGCCCAACAAGTTCAAACAkAAGTAC-CATCCCACAACAGGTGGTATTGGTWA 5 ATTCTTTTC-ACAATTATTGGTTTAAO%.CATTATGTTGAGCAGTGTATCATGAAAAAPCGmPzTCATCAG GlAAGCTTAA QRF am'no acici amence {S1Q ID NO-, 105} MKKINKCLTMFSTLLLI LT SLFSVAAPFDDAT DTVTLKVMPQAAFDNFTEGTKGKNDSDYVG-NDL ESY FOSTOA 'KE IKOAFF'VFKNIETG,'TKEFITENG,'KEV DTLEAKDAEGGrAVLC:GL TKDNG-FJ.FNfTAELKGI YQ1 V 101 ELKEKSNYDNNGS 1- LADSKAVPVK1 TLPLVN'NQ WVIXD.AH I YPKNTETRFQVDKNFA %DEDLDYTDNRKDKGVI VJSATVGDKSYIVGTILKSSDYKELVTDS~4TKG LTFNNtlNVKVTLDGEDFPVLN4YKLVTD'DQGF RLA N4kI GAAVAAA AKDEDVSEI KITYSAT VNGSTTVE 1PTDI LYNPES i'ETPNEKIDAD T ITDAW AVIKAl FTLQEKQTDGTWV1WTlAST1EATKP SRFEHITFTGLDNA KTYRVVERVSGYTPEYVSFKUGV?' I ENNE-NS DPTP IN 232 KVVTYGRKF-VKTNQANTEJSAOATFIV KEGKYLA.RXAGAAtTAEAKAAVK TA.t 15 LA1LDEA74VKAYNDLTKEKQEGQEGKTALATVDC)KQFG&CZNDMFVKANYSYEWVAPDKKAtDNVVELISNAGGQFEI T GLDKGTYGLEETC)APAGYATLSG DVNFAEVTATSY SKO,'ATTDIAYDKGS-VK KDAQQVQNXKVT IPQTGtJGT I LFTI I GISIXMLGAVVIKRQSEEA $train 1C250 20 ORE DINA sequence (SEQ ID NO:0 1481: ATGAAAA TCAACAAATGTCTTACAPATOTTCTCGACA.CTOCTATTGATCTTAQGTCACTATTCTCAGTT GCACOAGCGTTTGQGGACG3AQGCA-ACAACTGATACTGTGACCTTGCACA AGATTGTCATGCCACAkAGCTGCA 'TTSATACTTTCTGAAAGTACAIAAGOTAAGAWGATAGCGATITATGTTOOJITAA3ACAA'!ATTAATOACCTT A AATCTTATTTTGGQT CAACCGATGCTAAAGAkAATCAAC-GGTG CTTTCTT GTTTTCAAAAU T4AAACTGGT 25 ACAA AATTCATTACGVAATGGTAAGGAAOlTCOATA'CT TTGOA.AGCT ZAAAGATSCTGAAfGO T' GTGCTG TT CTTTCAGGGTTAACAAAUAGACAA4TGGTTTTGTTTTTAAACTGCTA7AGTTAAAAO GAA7 TTTACCAAAT,'CGTT GTA-TTGPAAGJATCAAACOT2CATAAAAQUGGT TC TATCT TGGCTGAT TCA ACAGTTCCAG TTAAA ATCAOTOTGQTTGGTA-AOAACCAAGGTGTTGTTAAGATGCTCCATTTATQAA.GAATACTGAAA.CA AAACCACAACTGOTLAAACTTTOCA.?GATAAAGATCTTGATTATACTGACAAPCCOAAAAQ AACAAAGS ' TGTT 30 GTOTOAGOGACAG TGGTkGACA7,AAAn .ATAZCATA GTTGGAACAAPAATTCT-TAMAGGC-TCAG ACTATAAkG ACArTGGTTTGGACTG-ATAC-CATGACTAAA .GTTTGACGTTCAACA.ACA.k43.TTAAA:TAACATTGGATGGT GAAGCATITTTCCTGTTTTA-CTAC-A-AAC.TCGTAA-CAGA4TGACCA LAGGTTTCCGTCTTGCCTTGAATGCAACAL CGTCTTGC-AGCnGTAGCAGC-AGCT GC-AAAAG,,-AC.AAGAT GTTG7,AATCAAGATCACTTACTCAGCTACGGTG AACGGCTCICACTACTGTTGAA ATT4CCAG AA2ACCAATG-ATGTTAA' ATT4GGA.ZCTATGGTAATAACCCAA ICGGAA 35 GAAGIGAACCACnA GAnGGTACTCCAGCTAACCAAGA.ATTAAAGTCATTAAA.GACTGGGCAGTAGnTGGT ACAA1%TTA.CTGATGCTAAT~lGTTGC-AGTTAAA2 kCTATCTTTAC-TTG-AAG--AAACAAACG GATGGiTACATGG GTGN, ACGTTGCTTCACACGAA. GCAA. CAAAA CCATCACIGCTT TGAAG rATACT TTCAiCAGGTTTGGATAtATGCT AABATAGCTGCA-iGG'ACGTCATCI'PAA-GATAT..lA4TGGTGT A CTATCAAGAACAACAAA'-3AACTCAAATGATCICAACTCCAATCAACC-CATCAG AACCAAAAGT4GGTGACTT AT 40 GGACGTAAATTTGTGAP-A.CAAATCAAGCTAA,,CACTGAACGCTTCGCAGGAGCTAkCCTTCCTCGTTAAO;.AA GAAGGCAAAT-%-ACTTG.ZCACGTAA.AGCAGGTGCtIGCAACTGCTGM JCAAA3sGGCAGCTGTAAAMACTGCTPAM C TAGCA TTGGATGAkAGC TG TTAAAGC TTATAAC GAC TT GAC TA AGAAAkAACALAGAAGG CCAAGAAGG TAA-A A CAGCA T T GGCITAC T GT TGATCr-AAAA-ACAAAAAGC TTACAAT GAC GC TT TT G TTAA.AGC TAAC TAC TCAT AT G AAT GGGTTGCAATAG- -kGTGATATGTTGTTAAATTGATCTCTAACGCCGTGGTCAATTTGAAATT 45 ACTGGTITGGATAAA.GGCACTTATGGCTTGGAAG AAaCTCAAGCACCAGCAGGTTATGCGACATTGTCAGGT GATGTAA ACTTTGAAGiTAA;CTGCCACATCAITATAG (CAAzAGGGGCTACAAC-TGAC-ATACGCATATGATAAAGGC TC TGTAAA, AAAGATGCCCAAICAAG TTCPAACAA.A-AAAGTA'ACCAT'CCACA-I AACAGGTGGTATTGGTACA ATTCTTTTCACAA TTATT-GGTTTAA GCATTTCTTGGAGCAGTAGTTTCATr A?.I.ACGTCAATCAGAG GAAGCTTAA's 5 0 oaR amino acid aSf e~iece (SEQ IV NO: l1t): ?AKKINKCL TMFST LLLI LTSoLFSVAPAFADDATATDTVT LRKh I4RPQAAFDN FTEGIEKNKDSDY'vGKQINqDL KSY FG STDAKE I KGAF*PV FlKETG PKF I T 4 SNGKEVDTLEAKDAEGGAVLSG LTKDNGEV FNTAKLKG IYQ IV EL17KEKSNYDNNGS I LADSKAVPVK I TLPIVNNQGVV/KDAH I Y PKNTETKPQVDKNFADKDLDY TDNRKD GV VSATVG DKKEY IVGT I LKGSDYKXLWTDSMKGTFRVVTL>SEFPVNIYKV~TDrQGFRpLALN AT 55 GLAAVAAAAK DK DVE I K 1 T YSATVNGSTT VE I PE TNDUKLDYGNN PTEESE PQEGTPANQE I KV IKDW4AVDG T I T DANV AVEA FTLQEKC)TDG,,-T;tNNASH EAT K PS RFEHT FTGLDNAKTYRVYE RVSGYT PSYVSEX.NGVVs, TI KNNKNSNDPTPI NPSEPKX%-/TYGRKFVKTNQA.NTERLAGA7TFLV1 KKEOKYLAXRKAGAATAErAAV KTAX. L ALDEAVKA"YNDLTKEE{QEGQEGKTALATVDQKC)EA.YNDAPJ .KANY&IEWVIADKF ADNVVJKLISNiAGGQFEI TG-LDKGTYGLEETQA PAGYnTLSGDVN 1FEVTATSYSKGATTDIAYDKGSVKAQ' tNKKVT I QTGG1GT 60 ILFTI IGLSIMLGA:VV\t-KKRQSEEA -89 Strain 1C251 ORkF DNA sequ ence (SEQ. ID NO: 149); AT GAAAAAAAkATCAACkAMTGTCTTA CAATCTTCTCGA CACTGCTATTGATCT TAACGT-ACTATTCPCAGT T 5 GCA CCAGCGTTTGCGGACGAC^GCAACA.ACTCATAC TGTGACCTTGCACAAG ATTGTCATGCCACPACCTGCA TTTGA.TA.%CTTTATAAC kGTACAAAtGGTAAGAATGATAGCGATT ATGTTGGT'AAACAAATTAATGACCTT AAATCT TAT TTT1GC'TCAACC-GATGCTA~AAGAATClA GGTGCTTTCTTTGTT TTC ATAATGGT ACAA'AATTCATTACTCAAA-ATGCTAAGGAAG TCGATACTTTGGnAPGCTAAkAGATGCTGnAAGGTGGTGCTG-T CTTTCAGGG TTAkACAAAAGA .CAATGGzTTTTGTTTT AACACTGCTAAGTTAkAAAGGAA'TTACCAAATCGTT 10 CAA TTGAAAGAAAA.ATCAAAzCTACGf ATAACAA-CGGTTCTATCTTGGC-TGATTCAAAl-AGCAG TTeCAGTTA-A ATCACTC-TGCCATTGCTAAXACAAC-CAAGGTGTTGTTAkGATGCTCACATTTATCCA AGAATA-TG?-AACA AAACCACA AGTAG~rATAACA.ACTTTCC'AGATA 1AAGATCTTGATTATACT-ACAACCQGAA-AACACAAGCGT-T GTCTCAQGCAljCTTG( iTQCCAAAAkGLTGATAGTTG3AACAA-AAATTCTTA,AGGCTCAC-ACTA'%TAAGfz AP.ACTCDTTTCGACTCATAGCATCACTA.AACGTTTGACGTTCAA, CA.AC-ACGTTA.7AGTAACATTGGATCCT 15 G AAGATTTTCCTGTTTTA2'AACTACAAAzCTCG' AAtCACATGA~CAAC.kGTTTCCGTC'TTGCCTTC-,ATCCAACA (5CTCTTGCAGCAGTZACCAGCAGCTGCAAAeAGACAtAACATGTT3AAATCAAG-ATCACT4TACTCAGCrTACGGTG AACCGCTCCACTACTGTTGAAATTCCAGAAAkCCAAeTGATGTTAA-TTGCAtiCTATCGTAlATAACCCA'ACCGAA GA$'AjGTGAACCA1CAAGAAGGTACTCCAGCTAA.CCAAQAAATTAAPGTCATTAAAGA -,CTGGGCAGTAGATGGT nCAATTACTQATGCTMkTGTTGCAGTTAAACC'G'TATCTTTACCTTGCACAAkAA$PAC;AAACGGCATGGTz';CA GG 20 GTC AACGTTG CTTC-ACACCAAG4CAAC-4AAACCATCAC(GCTTTGAAICATCl-TTCACAGGTTTGG;ATAATG-CT AAAAQTTACCGCC3TTGTC"GAACGTGTTAGCGGCTACACTCCAGAZATACCTATCATTTA AA ATGGTGTTGTGQ ACTA.TCA-AGAAC-AACP-AAAACTCAAATGATCAACTCCAATCAAZCCCATCAGA;ACCAAAAGTGGTGACT ThT' GGAC-GTAAATTTGTGrAAAACA&AATCAAGCTACACTG-ACGCTTGGGAGGAGCTnCCTTCCTCGTTAA A.AA GA AGGCMATACTTGGCACGTAAnGCAGSTGCAGCAACTGC TCAzAGCAA-ACGCAGCTGTAAAA'ACTGCTAAA 25 CTAGCATTGGA.TGAAGCTGTTA-AAD-CTTATAAClrGACTTACTAAGJAAACAAGAAGGC-CAA ,AGGTAA ACAGCCATTGGCTACTCTTGATCIIAAAACAAAA4-AGCTTACAATGACGCTTTTGTTAAAGCTAACTAGATCATAT CAATCGSTTGCAGAT2-AAAAAGGCTGATAAT GTTGTTA~AA-TTQATCTCTAACGCCCGTGGTCAAT4TTGAAATT ACTGGTTTSGATAAA C-GCACTTATGGCTTGG AAG,,AACTCAA'GCACCAGCACGTTATGCG-;ACATTGTCACCT CATGTAkCTTTGTACTGCACTI'ACCAGZGGGCTACA,CTGACATCGC3ATATAAAGC-C 30 T.CTGTAAAiAAAGATG-CCCAACAGTTC2AAAAAAAACTAAPCCATCCCACAAA CAGGTGGTATTGCTACA ATTCTTTTCAICAATTATTGRTTTAAnGCATTATGCTTGGAG-CAGTAGTTATCATAAJI.AAACGTCAMCAGA GAAGC'TTAA kRF amtino a i d_ sqence {S'E Q IDNO: 107): MEKI IKCLTNFSTLL1 1,T SlFSVAPAiFADDA %TTDTV TLHKIV1'I.PQAAFDA FTEGTKGKNDiSDYV,;GKQINOL-T 35 KSYFCSTDAKE IKOAFFV'FKNETGTKFI TENGKEVDTLEAKDAEGCAV'LSGLTKDNGFV1FNTAKLKG IYQIV VSATVGDKKEY IVO7TKILKGSDWKLDnTDSM KGLTFNNVJKVTLDGEDFPVLNYKLVTDDQGFRLALNAT GLAAVAA'sAAKDKEITKITYSATVNIGSTTVEIPETNDVKLDYGNNPTEDSEPQEGT-PANQEIKVIKD&ADG 40 T 1KUNKNSNDFT PINPSEPKW.VTYCRKFKTNQNJTERLAATFLVKEGKYLARKGAATEAKAVKTAK LALDEA^VKAYNDLTKEKQECQEG-KTAA. TVD)KQAYNDABEVANYSYEKADKSDNVTVKLI SNAkGCQFE I TGLDKGTYGLEETQAPACYATLSGDVNMFEVTATSYSKGATTDIhYDKGSK KDAQQVQNKKV7TI PQTGGIGvT ILFTI'ICLSI4LAVIM KKP.QSE-EA 45 Strain IC252 DEW DNA sequence (SEQ ID NO: 150): ATGXAAAAAATCAAkCAAATATTTTGCAGTCTTCTCGGCATTGCTACTOACCGTAAzCATCATTGTTCTCAGTT GC1ACCAGTGTTTGCOGrA. AGAACAAAAACTAC TGACACAGTCACC TTGCAC-AAGATTGTCATGCCTCGAAOkCT GOATTTOAC GGTTTTACTGCTGGTACAAAGCGTAAGCGATA.ATACTGACTACGTTGGTAA.ACAAA TCGAAGC 5 0 CTTAA-AACTTACTTTGGCTCAGaCGCGA-AAz;GAA TCGCAGGTGCTTACTTTGCTTTCAJ4 ATGAAGCT GGTAOTAAATACATCAO TGA;AAATGGTGAoAGAAT-('TGATACTTTG;GATACAAC(AGATGC-CAA,,AGGTGG.T.IGCT GTTCTTAAAGTTTAACACAGCATGGTTCI .T -TAACACTTCT.AATTAAPCAGGAACTTACCAAATC GTTGAATTG-AA.,AA~AAATCTACATAC-AACAPACGA,7TGGTTCTA TCTTGGCTGA TTCAAAA!GCAGTTOCAGTT M-AATCACTTCcATTGTACGACATGGTTTG-TTAACGCTCACTTTATCCAAAGAAATGAA 55 ACAAAACrCACAAGTAGsATAAGAACTTCG CAGATAAzAGAA CTTCATTATCGACAACAAP.AAAGACAAGGr A-CTGTCTCAGCAITCTGTTGGTGA TGTTk-,AAXIATCATGTGGPiACAAtACCTTAAOTTCA GACTAT AAGAAATTAATCTGGACCG,-ArAGCATGACCrAAAGD.,-GTTTOGACTTTC AACAACC'ATATTGC''TGTA.ACAT TGGAT &GTG .AACTCTTG~AT& CTACAAAzTTAGAA6ACTTGTAGCA-GATGAC-CAAGGTTTCCGCCTTGTCTTGACC-AC AIA GGTCTTGA11OCAGTGGCVPAAPCCGCAA, AAC'AAJAAGATGTTGAAAZTCAAGATCAC-TTACTCACCT ACT 60 TTGAACGGTTCTCTGTCGTTOAkAGTTC-TAGAA ACCA ATGATGTTAATTGGACTACGCAACAACOCCAOA.

-90 ATTGAAAA7lTGAsCCA~zAAGAAGGTATTCCACTTC-ATAAG AXAATCACTG -TAACAAAAP~CATGGGCAGTAGAT GGCAATGAAG TCA.AT.AG CAGA TGAAiCAG TT GAT GCT GT C TTCAC C T TCAAG TTAIAGAT GGT GCAA.A TGCGTGAATGTT3ATTCAGCTA",AAGCAACAGC TGCAACTAG CTTCAAA;sCAzCACTTTTGAAAACTTGGATAAT GCT AA2ACTTCACCG2GTTATCGAACGTGTTAGCGGCTA CGCTCCAGAAT.UACGTCTCAbTTTGTAAPATGGCGTT 5 GTAAr-C4TCAAGALACAA(>AAAC-TC.AAATGAG'CCAkACTCC'-AA"TCAACCATCAGAACCAAPAAGTGGTGACT TATGGACGTAAATTTGTGA;AACAAATAAAATGGAAAG,,rAAG rGCTTGGCAGGrAG CTACCTTCCTTGTTAA,"G AAAGATGGC-AAG TACTTGGCACGTAAA TCAkGGTGTTC-CAiACGATGC"AGAAAA,-AGCTG5CTGTAGATTCAACT AATCAGCATT GGATGC TGCTGT TAAGCT TAAAT GATT TGACTAA GA 4 IAACAGAGGTCAAGATGGT A-AATCAGCATTGGCTACCGTTAGTGAAA? ACA,-z AAAAGCTTACAA74TGATGCCTTTGTTA-kAGCTAAC'TAC TCA 10 TACGAAITGG GTTrGAGATA3-AAATGCTAAGAlATGTTGTTAAAI TTGATTTG TAAGG'rATAAAGGTCA 4AT TGAA ATTACTGGC-TTGACTGAAGGTCAATACTCATTGGAAGA. ,AAAGCACCAACTGGTTATGCTAAvTTATCA GGTGATGTTTCGTTTAAJGTTATG-TCTTCATACAGTAAGGTTCTGTAAGATATTGAGTATACCCA GGTTG TAAAAC TAAAkGA TGCACACAAGTTATCAATAAG,-AAGG T TAC TAT TCCACAPkACAGGTGGTATTGGT ACz'AATTTTTTTCACAA;u"TTATTGGATrTAAGTATTATCTTGGACGGTAGTTATCATGAAAGACGTCAATCA 15 GACGGA'AGTTTAA )RF amino acid sequence (SE.2 ID NO- 108) MICINKLTMS~hLI LFVAPFADA~hV'LHIVMFPQLAFDNFTEGTKG .NDSDYVGKQINDL *SYFGSTDAK I KGArrV YFETGrKri TENGKEVDTLEAKDiAEGGAVIJSGLTKDNGF7 FNTAKLKGI-YQIV ELKEKS. YDNNGS ILADSK AVPVK ITLPLVKNC)G\ WEAX IYPKNTETKPQVDKNFA %DKDLDYTDNRKDKGV 20 VSATVGDKKEY IVGTKI LKGSDYKKLVW;TDSTXGLFTVKTLDK7iEJX~ DFVL NYtLV'TDDrQGFLA LNAT Gl.'AAAKDKDVE -I lTYSATVNGSTTV;E IPETNDVKLDYGNI4PTEESEPQEGT PANQEI KVII{DWAVDG TI TDANtVAVqKAPIFTLQEKQTDGTWVNVASHEATKPSRFE~ITFTGLDNAKTYPY'!VERVSG 'TPEYVSFKNGVVI~ T IKNNKNSNDPT PI1NPSEPK'iJVTYGRKF.L ,TNQAN TERLA'4GATFLVKKEGAYLARKAGAATAEAKAAVKTAK LALDEAVKFAYNDLTKEI'IQECGQEG KTALATVDQKQKAYN DABV KANYSYEIIVAD-KKADN',TflLI SEAi GGQFEI 25 TGLDKGTiGLEETQAPFAGYATLSGDVN FEVTATS 1SKGATTDIAYDKGSVKKDAkQQVQNKV 1? PQTGI OF CRY is sequence (SEC TD NO 151). R0 A T7'A utT7AAF. TTTAAT'T-TG,,.CGTTGTTACTATTCC.-T GCACCAGCGTTTGCGGACOACGTAACAA %CTGATACTGTGACC-TTGCOAAG ATTGTC-ATGCCACAACTGCA TTTCATAACTTTACTGA.AGGTACAAA GGTAkAGAA TGATAGC GATTATGTTG-TAAACAAATTAATGA7;CCTT AAA TCTTATTTTGGOTCAATCCGATGCTAUAAATT7AGGGTGCTTTCTTTGTTTTCAAAATGACIACTGGT ACA',AAATTCATTACTG AAA,,ATGGTAA GGtAOTCGATACTTTGGAAl GCTAA -AGA TGCTGAA GGGTGCTGTT 35 CTTTC AGGGTTA.ACAAAAG.CACACTG GTTTTGCTTTTAA CACTGCTAAC.TT)-AAA.GGAAOTTAC(>4.ATCGTT GAAkTTGAAPAAAAA.TC.V.aACTACGADTA4ACAAC GGTTCTATC'TTGGCTGATTCA AAAGCAGTTCCIAGTTAAAk ATCACTCTGCC-ATTGGTAA~ACAACCAAGGTCTTGTTAAA7.GATGCTCACATTTATCCAAlAGAATACTGAAACA AAAirCACA'sAGTAGATAAiG AClTTTOAGATj'AAAOATOTCATTATCTAC'ACCAAAGACAAXGTC TT GTCTCAGCCGACAG(TTGGTGACAAAr.AAG-AAT..ACATAGTTGGAkCla-AAATTCTTA.AlAGG CTCAGACTATAAfG 40 AA-ACTGGTTTGGACTGATA GCATGACTAA AGGTTTCACrGTTCAACAA CAAO-GTTAAA PGTACATTGGATOG-(,T A.VATTCGTTV CA~'ATG~AA T~ AGTTCTTGCTIIGAC GGTGTTGCAGC-AGTAGCAGGTGCTOGZA4AAGACAiAGATGTTGAA? 5TCAAGr;ATGACT TACTC-AGCTACCGTG, AAOGGCTCCAC-TACTGTTGAAG7TTCCAC, AA- CAJGATGTT'A,,-TTGC 7 ACTATGGTeATAAOCCCACOGrA GAAGk-TGAAGkCACAAGAA .-GGT'ACTCAG;CTAkACCAAGAAA.TTAA.AGTCATTAAAGACTGGGCCAGTAGATGGT 45 ACAATTACTGATGTTAATGTTGC-AGTTiAA'AGCTATC.TTTAC-CTTGCAAOAAALZCAAA-UCGGATGGTAC(.ATGG GTGA7,ACGTTGCTCC.CCG;AAGCAA-CAAAkACCATCACGOT-TTGA ACA I.CTTT-CACAGG2TTTGGATAATACT AAAA.CTTACCGCGTTO TCGAAC-GTGTTAGCGGC AC-ACTCCAGAATATGTATCATTT1AAAAATGGTGTTGTG ACTATCAAG,-AACAACAAAAACTCAA.ATGATCCAACTCCAATCAACCCAT-CAGPAGC-.AAAGTGGTGA;CTT AT GGACGTAA ATTTGTGAA-AACAAATCAAGCTAkACACTGALACGCTTGGC-AOGACC-TACCTTCCTTCTTAAGA.A 50 GAAGGAAA-ATACTTGCCAC-GTAAAGCAGG-TGCACA2 AACTGCTG-AAGCAAAGGi -CCTG-TAAAAACTGCTAAA OTAGOATTGGATCA-AGGTGTTAAAGC-TTATAACGACTTGACT3AAGAAAACA;-AGAAG,GCAAGAGG.- TAA ACACCATTGCC TAC' TTTTCAAMACAA.AAAGCTTACALATG AC GCT TTTTAAAG- CTAACTAC.TC'ATAT GAA~tTGGTTGAAT-;AAGG CTGATPJAGTTGTTP-TTGAITCTACGCCGTGGTCAT'TGAPAVTT ACTGGTTTGGALTVAAC-GCACTTATAGCTT',GAAGAZ %CTCAAGCACCACCACCTTATGCGACA TTCOAGGT 55 C-ATGTAA,'ACTTTCAAGTAACTGCCACATCA'TATAGCCAAAGGGGOTACAA;-CTGACATOGCATATC-ATAACGrA TCTXGTJAAAAACAW-AGO CCOAAPCAAGTTCAAACAiAAAAGTAAzCCATCCG'ACAAzACAGGTGGTATTGGTACA ATTGTTTTCAC AATT ATTCGTTTAAGCATTATCTTGGG AGTAGTTGTCATGAA.AAGTCAATOAGAG GAAzGCTTA ORF amino acid sequence (SEQ ID NO: 109): IMKKINKCLTVFSTLLLX LWSLFSVA .knFADDV TT-DTVTLaHKi V NPQAAFDNFEGCTKGENOS -tVQJKQ INDA 1{SYFGSTDAKEI1 GAFFYFREETGTKFT TENGKEVDTLEAKDAEGGA'VLSGLTKDTGFAFNTA-KLKGTYQI-V ELEEKSNYDNW;S ILADSKAVFVKI1TLPLVJNNQGV'VKDA H I YPKNTETKPQVDKNFADKDLDYTDNRDKGV VSATVGDKKEY IVOTKI LKGSDYKFLVNITDSMrTKGLTFNNNV KVTL-DGKDFPVLNYELVTDDQGFRLAL-NAT 5 GLAAVAAAAKDKDEIKI TYSATVN'eGSTTVFVPETN',DV:.LDYGNNPTFEESEPQESGTPANQEIFNI DAVDG 'rT TDNV7,-AI FTLQ(EKQTDGCT~VNVA?,SHEATKPSRF-EHTF-TGLDNTKTYRVVERV %SGYTPEYvS FK FSVV 1TI KNNENJSNDPTFI NSS- E OK TYGRKI--FT. QAI4ERLAGATFLVKK-EGK<YLARP,'nGAATASMAAkVKTAK 5 LALDEAVt3KAYNDLTKEEQE)PGQEGKTALAiTVD;QKQKAYNDAt'FVJKANtYSYEWViDKKAN'VL19AGG-QFEI S TOLD TYSLEETQAAGIAYATLSG5DV NFEVTATSYSKG2ATTDIAYDKG.3,VI(DAQQNEKV,%T 1PQTGG( IGT IStrain IC254 OFF DNA seqtuence (SEQ ID NO, 152) ATGA2kkGAATCAACA.TATTTTGAATGTTCTCGGCATTGTTACTGACrTTT ACGTC-ATTG'CTTCAGTI 15 GCAVGAGCGTTTGCGG7ATGAAG-CAACAACTAATACAG-TGAC TTTGCAC.;A ATTTTGCA. ACCGAATCAkAAT CTTAAGAAnA4GTAACTTCGGAGGr:AAC .'tITCAGGTCTTAAC-GGAAAGATAAAGGGAGTATTTTA7 CTTGOTGGTTAC TTTGGC'-GAGGGATOTAA7AGA.AATCGA.AGOTGCGTTCTTTGGTTTAGC TTTGAAAGAAGAT -AAAGTGGTAAAGtCTGCAA TATGT T GGCP AG,GGTCAT TACCCACCTTA2XTT.A AGAT GGTACTCOTGAAAkTAAOAGTAPATATTGATGAGGOCGTGTC-TOGATTGACACCAGAGGGAGATAGTGGACTT 20 G TT TT CA ACAPC C A A-1G GATT GAAA G GC GA G TTT A AAPT T GT TG A A G T T ATC A AATG TAC T AGCA ACA AT AATGGTTCCGTCGTGGGTGCTTCAAlAAGOGGT TCCAGTTAACATOAOC.TOTTGCATTRGTAAATCAA-GATGGT GTTGTTGOTGATGCGCATGTTTATCCAAAGA,,AAOTGAAGAAAAACCAGMA.TTAZTAAA'lAACTTTGGThAAA CGTOAC A.AGCAAC TGCTACTGCTGAAZATCGGTAAAGTTGTTCCTTATGAAGT-TAAAA %CAAA.AATTCnCAAA. 25I GGTTCTAAATAC'-GAAA-ACTTGGTTTGG ACiAATATAATGTCA; AATGGTTTGACAATGGGTTCAACTGT TACC' CTTA AAGCTTCA&GGAACTACAG-AAAC%.TTTTC-CTAAGG ATAC AGACTATGAAC TTAGCATTGATG'CCCGTGGT TTCACATTAAAZATTCAGAGCTGATGGATVTGGGCAkAATTGGAAAIAGCAGCTAA%-AACAG CTGATAT'IGAATTT ACATTGAC TTATAGTGCTAC.'TGTTAATGGTCAAGCAPATTATTG ATAA; TCCAG AATCCAA TGATATC',AAT'TG TC-GTATGGTAA CAAAzCCAGGTAATAGACTTGACT' GAAJCTTCCTG3TT'ACACCTTCAAGGG3TGA.AGTAACAGTT 30 GC TAAAA; CTTGGTC'TGACGGAATTGCACTC-ATGGTG TAA -ACGTTGrTTTACACATTGA-AGA TAAAGATAAA A C TGT T GC TT CAG TAT CAT TGA C AllXCAT C TAGGTACAT CGACC TT G GAAA TG G TATIC AAAT TTGAAk GTATCTGGTAACTTCTCGGGTAtAATTCAC-TGGTCTAGAAA ACn'iAATCATAiCATGATCTCAGXAdCGTGTTTCT G GT TACO GIAG TG C ATAA AT CTAGAAAAAT GG TAAAGTAASCCAT TAC CAAT A CCAAGAiT T CTGA TAAC CC A ACACCKC.TTGAACCCAACTGAACCAMAi;GTTGAAVACTCATGG''TAAGAAATTTGTCAAMACTA. TGAACA ^AGGT 35 GACCGTTTGGCTGGTGCACAAT TCGTTGTGA.AAA,,ACTCAGCAIIGG-,h4AATACCT TGCTCTTA,AG-CAGnTCAA T CAG AA GGTC AAAAXU1ACT T TAG CT GC TAA GAAAkT AGCCT TTA GAT GAAGC TA T C G-T GC TTATA.A.CAAG TT G TCTGCAAkCAGAkCCAAkAAAGGTGAtA.AAGGAATTAC'TGCA.AAAGAACTTATCAPkAACTAAACAAlGCAGATTAC GA,'TGCAGCCTTCATTGAGGC^TCGTACAGCTTATGiAGTGGATAACAGATAAGGCTAGAGCCATTACC-TAC.ACT TC-AAC'GATCAAGGTCAATTTGAAGTTACAGGTCTTGCAGACGGTACTTACAACCTTGAAGAA-ACACTTGCT 40 C-CGCAGG'rATTTGC-TAAGTTGGCAGGTAATATTAA GTTTGTAG-TTA'ATCAA-ZGGGTCATACATAACAGGTGGT AACATTGACTACGTTGCTAACAGCA-ACCAaAGATG CCACG4GTAGAAAi';TAAAAGGTAACAAzTCCCA C,AACAGGTGGTA ITTGGTACAA %TTCTTTTCCAATTATTGGTTTAGCATTAT-GCTTGGAGCAC3 :TA^GTTATC ATGO JXAAGA PCGCCAATCAA %AGGAAPGC-TTAA OFF amino atcid sevne(S!EQ 10 NO, 11Q) 45 MKFINKYFAIYFSAAL'TATSALSVA PAFADEATTNTVTAHIIK QTESNLNKSNFPGTTGANGKDYKGGAI SD AAGrYEGl-EGSKE I EGAFFALAALKEDKSGEVQYVKA;4KEG NKLT DALI EDOT SE ITVN I DEAViSGATFEGDTGA TNDATALTDVNRALTAGA~I-GNYAFRDKAPTATAE IGK'.VYEVKTK1IKGSKYENAV1WTDI NSNGLTIIGST VS AKASGTTETFAFKDTDYEASIDAGC.FTA(FTAD(,ALG&KEnKTsF'ADEFTATYSATVNlGQA1, IDN?ESND7KA 5o SYGNEPGX DATEL PVT PSKGEVTVAKTWSDGIAP DGVNVVr YTI;KD DKTVAkSVSA TKTSKGT I DAOGKE VSGNF SGKf'TGLENKSYMI SEYYVSGYGSAINLENGKV ATITNTKDSDNPTPANPTEFVETIiG zKKOVEi(TNEQG DLAGAQFVV.KNISAGK-YATAAXAQSEGQKTAAAK IALDEAA,IAAY SATDQKGEKGl TAKELI ETEQADY~ DA'AFI EARTAYEWI TDKARAI TYTSNDQGQF EVTGLADGTYNLEETLAPAGFAK,:AGNIK RFVVIIQGSYITOGG NI DYJANSNQKDATRVEFi{KFTl SQIGGICTI AFTI GAS IMAGAVVMKRRQSKEA OFDNA sequence (4SEQ ID NO: i53), ATGAAAAACAACAAATGTCTTACAATGTTCTCG-,CACTGCTATTGATCTTAACGTCACTATTCTCAGTT GCACCAGCGTTTGCCGGAzC( CCCACAACTOGAT-ACTG TO-ACCTTGCACAAGATOTCATGCCAAZAGCTOCA 60 -TTGATAACTTTAC'-TGrsGTCAAALGGAAAATATA-C ATATGTTGGTAtAC.AAA;TTAAkTG7AC-CTT AATCTTAT TTTGGCTCACGATGCTAA(3AAA-,VTCA-AGGTCTTTCTITTT TTCAA2-kAG.TGJ~ACXGGT ACAAAAT'CCAT TACT GiAAATGGTAAjiGCAIGT-CGATAC TT TGG3AiGC-TAz-AATGCTGAAGGTGG TGCTGT T CTT TCAGGGTTA.AAAAAGACAATGGTTTT GTTTTTAA-CA'CTGCTA*;AGTTI,AAAAGAA;TTTArCMATCGT GAT TGAAAG?2JAA-TC AAC TA"C:GATAA. CAA-,CGGTLTCTATCTTG-GCTG'.AT TfCAli.AAGCAGTTCCAGT TAAA 5 ATCACTCTCCCATTGGTAA ACAACCAAGGTG TTGTTAAA-GATGCTCACATT TACCA- ^AAGAAlTAC"TG AAAICA AAACCACAAGTAGATAAGAACTT TGC-AGATIA.;AGATCTTGATTTA"TACTAACGfGA3AGTT GTCTCAG Ci ACGTTGGTGACA,,-AAAAAG2AATkCATAG TTGGAACAPAAA ATTCTTAAnGGC CAGACTATAG M;A.CTGGTTTGGACTCAT,7AGCATGACTAAkAGGTTTGACCTTCAAC^AACAACGTTAAZAGTAA CArgTGGATGGT GAAGATTTTC'CTCTTTTAAACTACAA-ACTCGTAAkCAGAkTGACC-AAGGTTTC-CGTCTTGCCTTGAATGCA ACA 10 GGTCTTGCAQCAGTAGCAGCAG3CTGCAA.AAG,--ACAAAGATGTTGPAATCAAGATCACTTACTCAGCTACGQTG A ACGGCTCCACTACTGTTGAA,'ATTCCAGAtAACCAA.TTGATGTTAAATTGIGACTATGGTAATAACCCAA2CGGAA GAAAGTIGAkACC~kAAAGACTACT CCAGCTAACCAAGAAAT TAA AGTCATTAAA.GACTCGGCAGTAGATGGT ACAAT TACTGATGCTAATGTTGCAGT TAAGCTAT CT TTACCTTGCAAGAAFAACAIAACGAT GQTAC AT GQ GTGAAXCGTTGCTTCACI:fACAGCIAACAAAACCATCA4CGC-TTTGAACATACTTTCAC-AGGTTTGGzATA4ATGCT 15 AA-AACTTA-CCCGTTGTCGAA;CGTGTTACCGGCTACACTCCAGAATAC-GTATCATT=TA-AAAATGGTGTTGTG AC TAT CAAGAACAACAAACCAAAT GATC CAAC T CCA-1T CACCCATC AGAAC CAxAT 3GTGAC T TAw GGACGTZj~TTTGTAAVAAC.AATCAAGCTACACTGCGCTTGCAGGAGCTACCTTCCGTTAGA' A GAACGCA.ATACTTGCACGT2A-GCAGGTGCA(CAACTGCTGAGCAA GGCAGCTTAAAACTGCTA A CTA'GCATTGA'iTCJ~1CTGTTAXAQGCTTATAACGA.CTTA CT.AACAA.IDAAr.GAAGGCCAAGAAGGTAA 20 ACAGCATTGGCTACWCGTTGA ITCAAAAA?'-CAAAAASC TTACA ATGACGCTTTTGTT~aAAGCThACrTACTCA TAT GAATGGG TTGCACGATA'AAAAZlGGCTGATAATGT TOT TAA;ATTGATCTCTAACCCCGTGGTCAATTTGAA3 ATT ACTGCTTTGGATAA;6AGGCACTTATGGCTTGGAAGAPAACTCAAGCACCA.GCA2GGTTATGCGACATTGTCAGCT-' GATGTAAA CTTTGAAGT.AACTGCCACATCATATAGCAPAAGGGGC-TACAACTGAC-ATCGCATATGATA.AGGC T CTG TAAA.AAAAGAT GCC C.AACAAGT TCAAA-AC AAAAAA GTAA CCATC CCACAAAC AG G TGGT A TTGG TACA 25 ATTCTTTTCACAAA'TATTGGTTThAGCATTATCCTTGGAGCAGTAGTTATCATPA.hAACAGTCAZATCAGAG GAAGCTTA CI?.F amn cc eune(SEQ ID NO ill)' YSYFGSTDAKE I KGAFFVFKNETG TKFITENG KEVDTLEAEDAn~tEGGAVJLSGLTEDNqGFJ FNTAKLKC.IYQ IV .30 F5- 4<5-KSNY DNNGrSI LDSEA'VVKIT.LPLVN-NQGVV, KDAH IYPENTETEIPQVDKNFA DKDLDYTDNR{DKGV VS±ff IGEJEKEYIVGTEILKGSDYKKLVW~TDSMTKGLTF-NNNVPKVTLDGEDFPVLiNYKUvTDDQQ;FRLALNAT CLAA.VAAAAKDEDVrE TIlTYSATVNGSTVEI5 ENVLYNPESPSTAQIKIDAD STDAN-VAV,,KAI FTLQEfCQTDG-TWV~lNASNiEATJPSRFEHTFTGLDNA XTYRWVERVSGYTPEYV SFKNGW, TI KNKNSNDFTPI NFSEFJTYRK;TNQ'NT-ERLAATFLVKKEGYiLARAGAATEAKAAI FTAK LALJSAVKAYNDLEKEGOEKTAATVDQKAYDAFVAN tYSYEWADKADZPQVK'LISNAGGQFE I mGLDKGTYGLEETQvAPAGYATLSGDV4qF5VTATSYSE{GATTDIAYDKGSVKEDA QQVQNKKV,,TIPQTQQIG7 TLFP1 IGLSINMLGAVVIS4KMFKRQSEEA Strain M027 40 GM' DNA__seq-uence (SEQ ID NO. 154) ATG( 'AAKtAAATCAACAAATGTCTTAtCAATGTTCTCGACACTGCTATTGATCTTAzACG TCACTATTCTC-AQTT GCACCAGC-GTTT GCGGACGACGCAACAACTGAlfTAC'TGTC-ACCTTGCACAAuzC-ATTG'TCATOGCCACAAGCTQ^CA TTTGATAACTTTACTOG(R.,'TACAAAAGGTAArP. GAATGATAG CG'ATTATOTT-GGTAAACAA.ATTAATGA7CC-TT PA.ATCTTATTTTGGCTCA.A ,CCGATGCTAA. .AAATCAAlGGTGCT TTCTTTGTTTTCAAAi'ATGAA~ACTGGT 45 A^AAATATCG2 VThA.Are * GCGATACTTTGSAAGCTAMi~GATOCTGAPAGGTGOTGCTGTT CT TTCAGGiGTTAA ICAAAAG(ACAATGGTTTTGTTTTTAA2CACTGCTAOTTAA4AAGGAATTTACCAAAz TCGTT GA.ATTGAAAsGAAAA -ATCAAACTACGATAACAAICGGTTCTATCTTGG- CTG7ATTC7-AAAAQCATiGTCCAGYTTAAA ATCAC-TCTGCCAkTTGGTAAACAACCAAGGTGTT"GTTAPGATGCTCACATTTATCCAAOSA,4TATGASACA AAACC-ACAAGTAGAT AAOAAC T T TGCAGATAAAGAT C TTGAT TATACT GACAAC CGAUP.AGACAJ,QGGT GTT 50 GTCTC AGCGACAGTTGG-TGYACMiAkAGAAT-ACkAQTAT- GOAACAAAA%3%ATTC-TTAAAGGCTCAGACTATA iG AA.ACTGGTTTGGACTGATAGC-ATGACT'AAAzGGTTT'GACGTTCAACAACAAtCGTTAAAGTAACATTGG ATQG7CT -A.AGATTTTCCTGT'TTAAAlCTAC-AAACTCGTAACkSAT,-GACCAAG-GTTTCCGTCTTG-CCTTzGAATGCAAkCA GGTCTTGCAGCAGTAGCAGCAGCTGCAAAAG$lACAAAGATGTTGA.AATCAAGAT CACTTACTCAGCTACGGTG AACGGCTCCAC-TACTGTTG-AAWTCTCAGAACCAATOAl TGT4TAAA TTGGACTATGGTAATAACCCAA %CGGTAA 55 C-kAAAGTGAACCAC'AAGAAGGTAICTCCAGCTA ACCi.AAGAATTAAAGTC^ATTAA;AGACTGQGCAQTAGATGGT ACViATTAtiCTGAT(CTAATGTTGCAGTTAAGCTATCTTA CCTTGC AGAAAAACAA-ZACGSATGGTAC-ATGG GTGAACGTTGCITTCACACGAAGCAACAAAACCATCACGCTTTGAACAISTAzCTTTCAC (AGGTTTGGAlTAATGCT AAAAPCTTACCGCGTTGTCGAAiCGTGTTAIGCGGCTA CACTCCAGAA,,TACGTATCATTTAAtAATGGTGTTGTG ACTATCAAGAACAACAA.AAACTCAAAiTGATCCA.ACW'CCAATCA ACCCATCAzGAIACCAAAGTGGTGAGTTAT 60 GGA.CGTAAATTTGTGAI4AAG5A ATCAPAGCTAACACTGAACG( CTTGGCAGGO;AGCTACCTTC^CTCGTTAzGAA.A -93 GAAGGCA)TACTTGGCACGTAAAGCAGSGrGCAGCA.ACTCCTGASCAAAGGCAGCTCTAAAACTGC'-TAA CTAGCATT GGATGAAGCTGTTAZAPGCTTATA-ACGAC-TTGA'CTAAA.. GPtAAACARAAGCCAAGAAQrGTAA% ACAGCA'TTGGCTAGCTGTTGA' TCAMdJAACAAAAAiW-GC TTACAiATGACG-CTTTTGTTAAiAGCTAACTACTCATAT GAAPTGGGTTGCAGATAAAALAGGCTGATAATGTTGT TAAATTGATCTCTA'ACGCCGGTC-GTCAT TTGAAATT 5 ACTiGGTTTGGATAlA5GCAtCTTATGCCTTCGGAAG AAA, CTCAAGCCACCAG CAGGTTATGCGACATTGTCAkGT GATGTAAACTTTGAAGiTAACTGCCAC-ATCATATAGCAA~'AGGGGCTACAAC(TGAkCATCGCATATGATAAA.2GGC TCTGTAA-% AAJAGATGCCCA;ACAA4GTTCAAAAC.AAAAGrTAACCATC'-CCACAAP.ACGSTGGTATTGGTACA AT:TCTTTTCACAkATTATTG'GTTTAAG'ATTTGCTTGC-AG CAGTAGTTATCATGAAAAAACSTCAATC.GAG SA.AGCTTAA 10 QRF amino acidI seuence (E DN:12 MKI ILTFZhL LSFSV.APAADDA"TTDTVTLHKIVMFQAAFDN FTGTKGN,1D-DYVGK-,Q INDZ KSYFi3STDAKEI KGAFFVqFKNETCTKFI TENCEEVDTLEAKDAi EGCAVl.LSGLTKDNGFFNTA KLIJYQIV ELKEKSNYDNNGS 1 LkADSKAVPVKI TLPLVNNQGVVKDAN 1 YPENTETKPQVDKNF-ADKDLDYTDNR DKGV VSATVGDKEIEY IVGTKI LKGSDYKKLVN1TDSMTKGLTF-NNNVKV.''TLDCEDFPVNYKLVTDDQGFR-(I.ALNATz 15 GLa'7aJAAKDK.DVE IKITYSATVNIGSTTVE IPETNIDVI{LDYGNI 4PTEESEFQEGTPAN4QEITV I 1 DW',AVDG TJ KNNKNSNDPTPTINPSEPKVV-,TYGRKVIKTNQAN -TERLAGATFLVKEGKYLARKAG4AT EA{A AVKTAK TGLDKGTYGLEETQAFAGYATLSGDVNFEVTATSY SKGATTDIAYL)KGW'.KKDAWQQQNKKVTI PQTGIST 20 ILFTI IGLSIMLGAVVIMKKRQSEEA Strain 1C289 CRY DNA sequen-ce (-SE-Q ID NO. 155) ATGA1.,-AAGAk'AGArAPAATATTTTGCAATGTTCTCGGGATTGTTATTAkATTTTAACATCGTTGTTATCGGTA 25 GCTCCGGTA TTTGCTGCTGAGA -TGGGAAATATCACThAAkiACAGTA ACCTTAGAGCAAAATTGTTCAA 1ACATGC GATAkATTTL(CTAAQ CC~aATTTCGCAGGAATA;'AATGQATTSAATQGAAC(,GAAGWATAfGGCLAAAAC-TT ACTGACATTTCAkGGATATTTTGGGCAAGGTTCTA.AAGAA ATCGCCGGTGCTTTCTTTGCGGTTATG"AAT.GAA AG2TCAG-ACAAAAT-ATAT.CACAGAAAIC-TGGTAC'TC-AAkGTAkG2AAGTATCGATGCAGCAGG TGTCCTTAAAGGT TTGACiACTGA AAACGGCATTACATTTA',ATACTGCAAAG~tTTAAAAGGAACAT.ACCAAATCGTTGA.GTTGC m T 30 GACAtT'CTAATTATJikk ATGGTGACAAGTTCTTGCTGACTCAAAGCTGTCCAGTGLAAATC CTC m TT CCTTTGTATA AC.GAAGA 'AGCYAAiPTTGTCGTGGAG',GCTGAAGTGTATPCC'AAA..'GAATACAGAGAAViGCA--C.A '. ATGGACAAA.AACT-TTGCTAAA{3-CAA ATAAsATTGTTGAATGACAGTGATAATTCA GGTATTG CAGGTGGGCA GAC"TACGACAAAZTATCAGGCP,AAAAGCAAIAAGCTACTGCTGAAATCGGTCAAGAAATCCCTTACGAAC TT AAAAAAATCCAAAAAGGGTCTAAATAA';-AACC'TTGCTTGGGCGATACCATG TCAAATi'GG3TTTG)'CA 35 ATGGGTA;ACACTGTTAACT'TAGAAGC-ATCGTC-AGGCTCTTTTGTAGAAGGTACAGATTACAATGTTA.ACGT 3ATGACCGTGGTTTCACTTTG4AATTCAClGATACAC-GTTTGACTAACTACAAAAGACGA.A AA -T GCTGTTGAATTCACATTGAGATATAGCGCAACAGTTAACGGTGGGGCTATT GAT ACAAGCCAGAADAGCAAT5 GATATCAA-ACTTCAATAC-GGTAA- CAlAACCAGGTAAXA., AAGTAAAAI GAA ATCCG-AGTAACACCGTCAAATGGC G;ZATCACTGTTAGCAPIACTTGGGA^CAAAtGGTTXCA'GATTTAGAIGAATGrCGAATTTIGT-TTAT-ACCCTTAAA% 40 GATGGTGGA ACAGCTGTTGCCT CAGTTTCATTGACAAAAACA ACACCAATGGCGAAA-TCAACTTAG4GTAAT GGTATTAVTTTACAGTTACTGGAGGTTTGCTGGAlAATTCAGTGGTTGCTTAGTAXAAVCATCAT ATCTCAGAiACGTATCGCTGGTTATGGTA-,ATACAATCACTACTGGTGCTGGTAGTGCAGCTATCACCAA, TACT CCAGATTG-AGACAACCGAAzC.AGCACTTAA'4TCCAACTGA.ACCAAAiAGTTGTGNCA-%CGGTA.irAAA.7TTCGTGC AAA.ACIAAG-TTCGACTGAAAzCAGCAACGCTTGCAA ,GGTGCACAGTTCGTTGT TAAAGATTCAG CTGG3T-AATA C. 4.5 GTTGGATTGMATCATCTGGACAM ATCAGCTCA6ACAA-AGCTTACACAAATGCTAAAAGATGCTCTTGAC GC'TMtAA.TCGCACTTACACA-ACTTTCGCAGAC-ATCATAAG(GTACTAAA G-GTCAAACACCTAAAGCATl GAAATCAAAACTCTCAAS.ACCTACAATGGAGCCTCGATC3T.AGCTCGT-ACAG:CTrTACG-AGTGGGTAAOT A;ATh PAAGATGCTAAkCGTTGTT?.AAGTGiACTTCAPAACGC'-TG CGGTCAATTTGAAGTTAGCGGTCTTGCA ACTGGTSATTATMAGCTTGAAGAC7IAACACAAGCTGCAGCTGGTTAGGCTM'.ATTAGCAG7GTGATGTTGATTTG 50 AAGArTTGG-CACCCAAAGCAGAGACTCAGTA;CATTGATACATGCTAGCACAATA-AAAGAC GCTGAACCCATAG7-AAACA 7AAAACTCx'CTATTCCACAAVACACCTCGTATTGGTACAATTC'TTTTCACAA'TT ATTGGTTTAA %GCATTATGGTTGGAGCGGTAATTATCATGAAADAGAGGTGAzATCAGAGGAA;GCTTAA CRY amino acdIqene(E D NO: 113): 55 T D2SGYFGQGSKE IAGAFFA~vNME SQTEY ITEGT EVE S IDAAGVLEGLT TENGI TMTAlmKGT YQ IVELL DKSNYF PGDKLADSAPVKTLPLYNEEGIW(DAEVYFKNTEEAPQ IDKNFAEA-IKLLNDSDNSAIAGGA DYDKYQAEKA7%KATAE ICQ'E IPYEVKTK1'QKG3SEYKULAW VVDTM ,SNG-LTMGNITVNLEASSGSF-VECTDV-YNVER, DDRGFTLKFTDTGLTKLQKEAETQAVEFTLTYSATVNIGAATl, DDEPESNDIKLQYGNKGEKV} 7E Y PVT 2SNG El TVSKTWDKGSDLENANVV-YTLKDGGTA.VAzSVSLTKTTPNGE INLGNG IKFTVTGAFA.GKFSGLTDSKTYM 60 T SERI AGYGNTI TTGAGSAAI TNT FDSDNPT FLNPTEPEQQv'THGKTEVKTS STETERLQGAQEVVl/KDSAGKY -94 LALXKSSA T ISAQTTA YTWARTALDAKI A4YNKLSAD&QXI)GTKGETAKAE IKTA QDAYNlPAAFIVAlRITAYEAZIT NKEDANVVKV TLL ADGQFFNSGLTATGDYKLEETQA PAGYAKLA GDVlDFI VGNSSKADDSGNIDYTASSNRKD AQRIENK1(VTX PQTGGIGTTLSFTI IGLSIMICkLGAVI JMKRRQSEEFAJ 5 Strain 1C291 ATG A.A~zAAAATCAAkCAAATGTCTTAC. AATGTTCTCGACACTGCTATTGATCTTAACGTCA CTATTCTCAGT 2 GCACCAGCGTTTGGGGACGACGCAACA -. bACTGAT ,CGTGAJ2TTCACAAGATTGTCAT GC'CACAAGC-TGCA T TTGATAACTTTACTGAAGG TACAA7 AAGGTARGCAATG-ATAGCG ATTATGSTTGGTA.ACAAATTAATGACCTT 10 AAATCTTTTTTGGTCAGCCGATGC.TAAAG-AAATCAAGGGTGC-TTTCTTTGTTTTCAAAAA.TGAAA;CTGGT ACAAAATTCATTACTGAAAATGGTAAGGAAL; GTCGATAC-TTTGGAAGC-TAAAGATGC.GAAGGTG-GTGCTGTT CT TTCAGGrGTTPiAN^kiVAnCATGT TTT GTTTTAAGACAl T CrAAGTT'AAAGAATTTAC^.ATCGTT_ GAATTGAAAGAA.AAATCAACTCGATAACAA-GGTTCTATCTTGGCTGATTCAA.AGCAGTTCCAGTTAA 5 C1CTC.TGCCATTGCT-.TAACAACCAAGGTGTTGTTAAGATGCCCATATCAAA xA AAC 15 AAACCACAAGTAGATAAkGAACTTTGCAGATAAkAGATCTTGPATTATACTGACAA-CGA-AAGACAA.AGGTGT-T GTC I CAGCGACAGTT-GGTGA-CA,lAAA.rAATACA.TAC-TTGGA2ACAAA.TT-T-TAAAGGCTCAG ACTATAAG C. ITGGTTTGG'ACTGATAG CATGAstCTAAAG.,,CGTTTGACG TTCAACAAQ.AAC.G'TTAAGTAACAlTTG GATGT I GA'AGATTTTCCTGTTTTAAACTACAAACTCGTAAkCAGATGACC-^AAGGTTTCCGTCTTGCCTTGAATGCAACA GGTCTTGC^AGCAGTAGCAGC^AGCTGC-AAAAG.CAAAGCATGTTGAAATCAAG.ATCACTTACrTCAGCTACGG 20 AACGGC-TCGACTAC TGTTGAPkATTCC"AGAAA %CCAATGATGTTAAATTGGACTATGGTAATAACCAACGGAA GAAAGTGAACCACAAGCAAGGTACTCCAG OCTAACCAAGAzAATTAAAGTCATTAiAGACTGGGCAGTAGATG GT ACAkATTACTGATGCTAATGTTGCAGTTM4.AG7CTATCTTTACCTTGCAGAAAACAAC-GATGGTACATGG GTGAACGTTGCTTCACACGAAGCA,C~zAAACCATCACGCTTTGaAAnTACTTTCnCAGGTTTGGAThIATGCT ,aaAACTTACCGC-GTTGTCGAACGT4GTTAG CGGCTAC-ACTCC-AGIAATA.CGTATCATTTAAA-lAATGGTGTTGTG 25 ACTATO AAGAACAACAArAACTCAAATQATCCAA ,CTCCAATCAA,'CCCATCAGAACCAXM'%GTGGTQACT TAT GGA CGTAAAT TTGTGAACAAA' UTCAAGCTAt~CCTGAACGCTTGCAGGAGCTArCTTCCTCGTTAAGAAA GAA ,GGCAAAJTACTTGGCA' CGTAAAGC'AGG.TGCAGCAACTGCTG;AGCAAA IGGCAGCTGTAAAAJACTGCTAA, CTACCATTGSATGAAGCTGTTAGCTATACGACTTGACTAGAAAA,,VACAGAGGCC,'AGAGGTA A AC-ACCATTGGCTACTGTTGATCA-AAAACAAAAlAGCTTACA.ATGACCCTTTTGTThAAAGCTAACTAzCTCATAT AC TGGTTTGGATA.zGCACTTATGGCTTGG.2AGAAACTCAASCACCAGCAGGTTATGCGACATl-TGTCAGGT G ATGTAAA-CTTTGAA GTACTGCCACATCATATAGCAA' AGGGGCTACAA! CTGACATCGCATATGATAAGC TCTGTAAAA.AAA.GATGCZCCA %CACATTCAAAAC&.CAAAAnGTAACCATCCCACAAA.CAG GTGGTATTGGTACA ATTCTTTTCACAAi TTATTGGTTTAGCATTATGCmTGGAGCAGTATmTACATGAAAI4kUACGTCATCAGAG 35 GAAGCT TAA ORT aninio acid se&/ue nce (SEQ ID NO0: 114) MKKI-NKCLTM FTLLLI LSVAPAFADDATTDTVTLIKlV PQAAFDNFTEGTEKGiNDSDYVGKQINDL KISYF'GSTD AKEIKlAAF ZFPKNETGTKFX TEN:GKEVDTLEAKDAEGGAV ;'.LSGLTKDNGFVFNTAKLKG TYQIV EL-KEKSNYDNNGS ILADSKAVPVITLPLVNNQGVVKDAH I YPKNTETKPQVDKNFAkDKDLDYTDIRK~i. hGV 40 VSATVGDKKSY IVGTKI LKGS DYKKLTCDSMTEG(-LTF'NINUVkVTLDGEDFPVLN,\YKLVTD LDQGTRPLALNA-T GL,7AAAAAKRDVE TKlTYSATVNGSTTVE 'I PETNDVK LDYG14UPTEES EPQEGTPANQvEIKVIKDWAVNDG TI TDANiVAVEAT 4FTLQEKQTDGTWP%7dV ASHEAT,'KPSRFEHT FTGLDNAKTYRVVP.ERVSOGYT FEYVSFKN4GVV, 45 TGLDKGTYGLEETQAPAGYATLSGD' VFEVTATSY SEGATTDIAYDKGSVKEDAQQVQNKKV- T 1 QTGG 1(3 ILFlT IGLSZNCG, f.GAIMEKRQSEEA Strain IC04 ORF, DNA se-uence (SEQ ID NO. 157) 50 ATCA. %AAAATCAACAAATGTCTTACAATGTTCTCG7ACA C'TGCTATTGATCTTSACGTCACTATTC--T~CTT GC-ACCAGC-GTTTGCGGACGACGC-AA3CAACTGATACTGTGACCTTGC-ACAAGATTGT-CATGzCCACAAGCTGC-A TTTGATA.ACTTTACTGAA'GGTACAPAAAG GTAAG&'TGATzAGCGA TTATGT4TGGTAAACAAATTAATGACCTT ?&eiA%.TCTTATTTTGGCTCAACCGATGCTAAAG.~inATCAA GGGTGCTTTCTTTGTTTTCAAAjATGAAAiCTGGT ACAAAA4-TTCATTAkCTGAA AATGGTAAzGAAG TCO;ATAC-TTGZ ACTAAAGA.TGCTGACAGGTGGTGCTGTT 55 CTT TCAGGGTT ').AKVAGACAA TGGTTT TGTT TTTA.ACACTGCTAAGT TAAkGAATTTACCALTCGTT GAATTGA~.GAAJ.AA:TCPAAACTACGATrAACAAtCGGTTCTA ,TCTTGG''CTGA.TTC AAAGCAGTTC(.CATTAA.A ATCAC-TCTGCCATTGGTAAA,,'CAACCAAGGTGTTGT TAAAGATGCT-AC TTTATCCAATGAATCTGAACA AAA CCACAAGTAGATA.-AACT

T

JTGCAG.,A.AAAGATCTTGATTATACTGAC-AACCe-GAAAAGACAAAG;krGTGTT GTC TCnGCGA CAGTTGG T(ACAAAA,(A.ATACAT-AGTT-GG3AAAAAAT TCTTAA.AGGC,-TCAGACTATAAG 60 AAACTGGTTTGG ACTGATAGCATGACTAAAIGGTTTGACGTTCAACAACAPACGTTA-A.aTAACATTGGATGGT _95 GGTGTTGCAGCAGTAzGCAG.CAGCTGC.IAAAIGA2CAAAUGATGTTGAA ATCAlAGATCAZCTTACTCAGCTACG GTG AACGGQCTCC ACTACTGTTGT TC CAAAC2TAGTATGATAT GGTAATAACCCAzCGGAAk GAA% 1AGTG3AAPCC CAAGAA6GGTACTC-CAGC-TACCA~z.AATTAAA%-GTCATTAAAGACT-GGGCAGTAGATGGT 5 ACAATTACTGAT GCTAATGTTGC-AGTTAAAGCTATCTTTACVTTG^AGAAAAACAAZACGGATGGTACATGG CTGAACGTTGCTTC.ACACG-AACAAC;-AACCATCACGCTTTGAAtCATACTTTTCACA;%GGTTTGGATAATGGT JAAAA"CTTACCGCGTTGTCGAACGTGTTAGCGGCTACnCTC-CAGAATACGTATGATTTAAA.ATGGT AC'TATCAAGAACAAt CAA.AAACTCAA.ATGATCCAAC TCCAATCAACC-CATCAGAACCAAAAG TGGTGAzCT TAT GG^ACGTAAAPTTTQTGAA-kACAAATC'.ACTAA CACTGMACGCTTGGCAGGAGCTACCTTCCTCGTTA-G AA 0 GAAGGCATATGCACGTUAGCAG, TGAGCAAC TC TGAGC-AAGCAGC TGTAAAAACTGCTAAA C TAG CAT TCGATGAJAGCT G TTA~CTTAGCTATAGMAAGAGCAAGT ACAGCATTSGCTACTGTTGATCAPAAACAAAAAGCTTAlCAAITGnCGCTTTTCTTAAAGC -TAACTACTCATAT GAATGGGTTG .AC-AnlTAA.AAAGC TGATAATGTTGTTA'%AAT TGATCTC TAA-GCC-GTGGITCAATTT-AAATT ACTGGTTTGG ATrAAAGGCA'iCTTATGGCTTGGAAACTCAGCACCAGCAG GTTATGCGACATTGTCAGGT 15 GATGTAA7ACTTTGA.AGTA21ACTGCCACATCA7TATAGCAAA2GGGGCTA CAACTGACATC-GCATA15TGATAAAGGC TC T GTAPAA~ulA T GCC CAACATT CAAAC ACAAAG TA-ACC AT CQCCAC AAACVAGG TGG TAT TGG TACA ATTCTTTTCACAkATTATTGGTTTAACCATTATGCTTGGAGCAGTAGTTA.TCAGAAAAkAACG CAATCAGA.G GA-AGC TTAA .OPF amino acid so~qmencp (SEQ ID NO: 13,5)t 20 HKIKLTMFST ,LLLILTa SLFSV7APAFADDAT DTV& LHKINPQAAFDNqFTEGzTFKNDSDYVGR Q- INDL KSYFG.o-TDAREI KGAFFVF,-KNETGTKF-I TENGKEVDTLEAKDAEG-GA'VLSGLTKDNGVFVFNTAKLKGI YQI-V E LEE KSNY DNNGS I LADSKAVPVK1 TLQLVNNQGV7VKPAH I YPKNTETK PQVDKNEADKDLDY TDNEXDKGV VSATVGDRKEYIV GTKI LKGSDYKKLI~t' TDSM TKGLTFNNNVl'.KVITLDOEDFPVLNYKLV TDDQGFRLALNAT GLAA VAAAK~XDV E I I TYSATVNqGSTTVEI PETNDV'KLDYGNNPTEESE PQEQTPANQEI1 VI 1<DWAVDG 25 T I T DANVAVKAI FT LQEKQTDGTWVlNVA SH EATK P SRFE HT FTGLDNAKT Y RVE RVSGYT PE YVS FKNG V TI KNNKNSNDPTP2INPSEPKVVTIYGRKFVKTNQANTERLAGATFLKKEGYLARKAAATAEAKAAVKTAK IJAL DEAVKAYNDLTKE QEGQEGKTALAT-VDQ.QKYN DAFNY SYENA DKQ NVKLSAGGQ FE I TGLDKGTYGLEETQAAOY.ATLSODV NFEVTATSYSKGATTDIAYDKGSE,7KDAQVQ NKR7T I PQTGGIGT ILFTI IGLSINLOAl VIKKRQSEEA Strain 1C305 OR "DINA seq Iuence (SEQ 1D NO: 158): ATGAAAAAAATCAAkCAA-ATOTCTTACAATGTTCT-CO ACACTGOTATTGATCT LAACGTCAOCTATTCTCAGTT GCACC'-AGVCGTTTGCGG;ACGACG CAACAACTGATACTGTGACCTTG CACAAGATTGTCATGCCACAA',G- CCA 35 TTTGATAAOTTTAGTGA-AGGTACAAAA--GGT. AAAATOATAOCGATTATGTTOGGTAA7 ACAA ATTA%ATGACCTT AAA4; TQTTATTTTGGCTOAACCG ATGCTAAlAGA.AATCAAQGGTGOTTTCTTTGTTT TCAAA-ATGA-ACTGGT ACt'd ATTOAT TA'sCTG. AAATGGTA"AGGXAUGTCGATA' CTTTGGC.O -TAAA' GA IGCT.GA;AGGTGGTGCTG TT: CTTTOAGGGTTAACAAA..AGtAM TGGTTTTOTTT'TAAC'-ACTOiCTAAGTTAAA~AlATTTACCAAA..TOG'TT GATTTGAA14AGAAAA ATCARAC TACGATAACAACGGTTG TATC TTGGCTGATTCA AAAGOAGTTCCAGTTA.A AAACCACAAGTAGATAAPGAACTTTGCAGATAAA,4GATCTTGATT ATACTGACAACCOAAAAO .ACAA.AG GTGTT GTCTCAGCQAOAOTTGOTG. A-AAAAOAATACATA GTTGOAACPAAAATTCTTA.AOOCTCAPGACTATAAIG AAkACTGGTTTGGACTOATAGC.ATGAOTAAAGOTITOAOOTTOACAAI PCAAOGYTTAAASATAAOATTOG (ATO" GT GAAGATTTTCCTGTTTTAA.ACTACAZA3CTCGT.TAAAATGACCAAGGTTmTCCGTCTT GCCTTGAATOCAACA 45 GOTCTTGCAOCAG;TAO5CAGCAOCTGCAAAAGACAAOATGTTGA ,AATCAAGiATCAO TTACTCAOOTACGGTC AA2CGGCTCCACTACTGTTGRAAATTCOAGAAA CCAATGATGTTAA4ATTGGACTATGGTAATAACCCAACGGAA G'?1AAGTG, AACCACAAGAAGCTACTC-CAGCrTAACCAA"GAAaTTA?'AGTCA TTAAA.GACTOGGCA-PGT AGATGGT ACAA6TTACTGATGCTA4ATGTTGCAGTTAAAGCTATCT-TTACC'TTGCAGA.AAAC-'AAA.CGGATGGTAkCATGG G3TC-AACGTTGCTTCAC-ACGAG-CAACAAA.ACCATZCACGCTTTGAAOATACTTACGTTGATTC 50 AAA;ACTTACCGCGTTGTGGAACGTGTTAGOGGCTACACTC-AGAATCTATCAITTT-AAAIATO-GTGTTGTO AC-TATCAAGAACA.ACAAAAAaCTCAJA ATGATCCAACTCCAAl TCAACCCAT%CGAACC'AA2ATGC-TGACTTAT QQACOTA'.LATTTOTGOPJIACAT^AOOTOA.' CTGAAGC-TGCGAGTACTTCTCTTAGAAAV GAkAGGCA TAC-TTGGCCGTAAGCAGGTGCGCATCTGT(AAQC;AAC-GCGTGTIAAAfCTGClTAA C-TA.JSATTCGATOAAG CTGTTAAAO',CTTATAACGACTTOA-TAAAGAAAAA6CAAtGAGCCAAGAAGGTAAAz 55 ACASCATTGGCTACTGTTGATCXkAAAACAAAA-,,AGCTTACAlATGACGCTTTTGTT AAG,(CTAAC' (TATATAT GA ATGGGTTOCAGAmTAA5AAAGGCTGATAA6TGTTGTTA,%AATTGATCTCTAACGCCGGTGGTCAATTTGAAATT ACTGOTTTOGAPT-AAGGCACTTATGOCTTGGAAOAAACICAAGCACCAOCGO ~ TTATGCGAC-ATTGTCAGGT qATc3TAACTTTG AAGTAACTGCCOACATCTATA~GCPJx'tGGGGCTACAACTGACATC-CATATGATAAA %GGC TO GTAA-AAAAAO ATO.CCCPAACA4AG .TC.dxACAA1-AAAGTA',ACC-ATCCCAkCAAACAGGTGG'TATTGGrTACA' -96 GA&CTIAA ORFama a;id zs--une SQl O MK'IKCLTMFSTLLLI LTSLFSVA'PAFADDATTDTV TLHKIVMPQAtFDF-EGTKG NDSDVGrKQINI 4 5 KYcv STOAKE IKGA FFFNTGTKFITE NGKEVDTLEAKDAEGGAVL17SGLTKDNGF-IFl TAKLK-GI YQIV £LKL KSV!DfNN-GSI1LADKa VFPVK 3.TLPLV,-'NQGVVKDA.H1YFKNTETKPQVDKNFADKDLDYTDNRKDKGV VSATVGDKKEY IVOTA LXGSDYKKLVWTDSMT<OLTfl4NUVKVTLDGEDFPVNYK 2 VJTDDQG ALALNAT GIA -AAAAAKDKDVIE IKITYSATVNGSTTVE IPETNiDVKLDYGNNPTEESE PQEGT P-ANQVETKVIKDWAipVDG Ti TOANVAVE AI FTLQEKQTDGrTWVV ThSHEATKPSR, FEHTFTGLDNAKITYRVVERVSGYTPE?,VSFKNGVVI 10 T IKNNKNSNDPT PTNPSE FKWITYGRKFVKTNQANTERLAGATFLVKKEGI YLAPKAGA ATAEAK4AAV KTAK LALDE.AVKAYNDL.TKE'KQEGiQE&^TAL ATVDQKQKAfl DFAFVKANYSYE c'JADKKADWV~rTJPKLIaN-AGG QFET TGLDKGTYGLEETQAPAGYATLSG DVNqiETATSYSKGAT'T DT.AYDKGSVKKDA0QVQNKCVTI PQ-_TGGIG:7 1LFTI IGLS-IMILGAVIKKRQSEEA 15 Strain I0306 ORT DNA seguencc (SEQ ID10O 159). A.TGM.-AAATCAACA.AATGTCTTAGAATGTTG-TC-GACACTGCTATT.GATCTTAACGTOAO'TTTT'GAGT GCACCAGC'GTTTGC-GGAGGACGCAPACAAPCTG ATAO'TGTGACCTTOVGA. GATTGTCATGCO ACA"AGCTGCA TTTGATAACTTTACTOAAGGTAG-AAAGG CTAAGAATG AA~l CGATTATGTT-GOTjAAO!AATATGAilCCTT 20 AA ATCTTATTTTGGCTC.;AGCGATOOCTAAA,' GAAATCAAOGGTOCTTTGTTTGTTTTCAAAA' TGAAA CTOGT AGAAAATTGATTACTGIAATGGTA1GOAAIGTCGA 'TAG-TTTGGAAGrCTAA-,AGAITGCTGAAG GTGGTGCTGTT CTTTGArGGTPJXC.3A~AGACAATG.GTTTTG,'T'-TTAACAG.TG;CTPAGTTXAAAAGGAAC-VTTTAiCC AACGTT GC'IATTGAAAGLAAAzTCAAACTACO-ATAACAAG-GGTTCT ATCTTGGCTGATTCAAAAGCAG TGAGTTA .A AkTCACTCTGCOATTGGTA AAAACGAA;GGTGTTGTTtAAGATGGTCAGCATTTATCCAAA GAATACTG AAA; CA 25 AAG-' CACAAC-TAGATAAGAACTTTGCAGATAA AGATO-TTGnTTATAG7TGAGAACGAAAAt'GACnAAAGGTOTT GTGTGAGO GACAGTTGGT-G'CAAXAAGtAATACA5TAGTTG GAACAAAAATTC-TTAA.AOGC"TCAGA CTATAAG AAACTGGTTTGGAGTGATAG CATGAOTAAAGGTTTGACGTTCAA71CAACAGGTTAALAGTAACATTGGATGGT GAAGATTTTCCTGTTTTA.ACTACAAACTCGTAAA.GAGACCAGGTTTCGTTTGCTO-AATGGAAGA GGTOTTGCAGCAGC;TAGCAGCAGCTGCA.AAAGAGAAAGATGTTGAAlATCAA TGATCAGlTTAO-TCAGCTACGGTG 30 AA ,CGGQTCCACTA C TOTTGA ATT-CAGAaACCATGA TGT TAATTGGACTATGGTAATA2CCCAACGGAA GAAkAGTGAACCACAAGAACYGGTACTCCAGQ TA'ACCt'AAGAAATTAA AGTC'ATTA?1AGACTGGVGCAGTAGATGGT A CAATTAC-TGATGGC TAATGTTGC-AOTTAAAG ,'CTA. TCTTAGG.CTTrOAAAAAAAOAZAACQ2GAtTGGTAICATG GTGAA CGTTC'CTACAGGAAGGAPACAPAAACATCAOGCTTTGA.ACATACTTTCAG(-AGGTTTGOATAATGCT zAA.1ACTTACCGCGTTGTGGALACIGTT GCG GCTA'CCTCCAGAATAGCGTAT0ATTTAAA, AATGGTGTTGTG 35 AQ TATCAIAGA,2 AAAAAACTG'AA ATOATCCA"TCAA'-CAC'-CATAGlAACCAAVflTGGTOtAGTrTA GG'-ACGTA ATTTOTG VAAAAATCAAGCTA'ACAG!TGAACGOTTGGCAGGAG CTACCTTCTCGTT.AAAA GAAGGCAAA TACTTGGGAkCGTAAGCGCAGTCAGC\ GTGCTGAAGGAAAiGQ' GQTGTAAAAACTGCTAAJ- CTAGCATTGGATIGAAGGTGTTAAA Z.CTTATAAGICttCTTGAOTtAPAGAAAkAACAA'GjAGGCCnAOz.AAGGTnA. AGAGCATTGGQTAG.TGTTGATGAAAACA.AA2ACCTTACA.ATGA CGCTTTTGTTAAAGCTAAGTA2CTCAAT 40 GAA-TGGGTTGCAzGATAAAA.AGGCTGATAATOTTGTTA.AATTOATCTCTAA'%CGOCGGTGGTCAATTTGAAA,-TT AQTGGTTTGGATAAN-AGGCACTTATGGCTTGGAnGAAACTCAAGCAGGAGOAGGTTATGCGAGAT TGTCAGGT GATGTAAkACTTTGAkAGTPAG-TGOCACTC ATATAIGCAAA'GOGGGCTACAA 1CTG ACATCGCATATGAT.AGGC TCTGTAAAAAAGATGGCCAAC'AA4GTTCA-AAGAAAiA.AZGT-AAGCATGCCAG~A~zAAGGGTATTGGTA CA A TTCTTTTCACAATTATTGGTTTAGQATTATGCTTGGAGCAGTAGTTATCAT A,ZAAAA.ACGTCAA.TCAGAG 45 GAACCTTAA OPT amino acdIRunc SQ1 NO; 217): KSY"GSTDAKEIKGAFFV.FKNETGTRFI TENGREVDTLEARDAEGGAVL7TSGLTKDNiGFVFNTAKLKFGI Yoiv rLKEKSNYDNNOSI1LADSZ ,FVK1TLPLVNI IQGVVKD 111 TYPKNTETRPQVDKNFADKDLDYTDNP.KDKGV ItGLAAVz-.AAA DKDVIJ'%I.'gTYSATVIYIGSTTVEI PETNIDVKLDYGN.;NPTEESEPQEGT.PANQEK.VKDWA.,%VDGc *: "ITDiAVAVE,*A F'TLQEKQ~iTTVNVASNEATKPSPFEHTFTGLDNIAKTYRVVTERVTSGYT PEYVSFKNGVV, TI ElNKNISNDPT P -IPSE PKVVTYGR*KEVKTNQANITKIRLAGATFLV',K tEGXYYLA11RAGtAAEALKAVKTAKr .OSLDAVRAYNDLTVEKQEGQEGKTALAPTVDQKQKA.YNDAFVKANI SYEWV-ADKK.ADNVVr.KLTSNAGGQFEI 55 1 TGDKGTYGLEETQAPAGY(ATLSGDV-,NEFV,,TAT SYSKGAT DAYDKGSVKKDAQQVQNKKVJT I PQTGGI ST 11,, T. 1IGLS31MNLGAVV1IMKKRQSEEA Strain 10361 .ORE 01%' selu-nce (SEQ I O 6) ATGAU\AATAACAA ATGTCTT AC-AATGTTCTCGACACTGCTAT GATCTTAACGTCACTATT CCGY1 GCACCAGCGTTTGCGCAC'-GACCA-AAACTG'ATAC'TCTC-ACCTTGCACA'AGATTGTCAT-CCACI Xj'GCTGCAt' TTTG ATAA-3CTTTACTGAGGTACAAA.AGGTAAGAATGATAGCGATTATGTTGGTAAACAAATTAA TGACCTT A-AATCTTATTTTGGCTCAACCGATGCTA-AGAAATCAAGGgTGCTTTCTTTGTTTTCAAAlAATGA 1AACTGGT 5 nCAMA ,t-TCATTACTCAA.'ATGTA %AGGAAG TCGnTACTT'.TGG .ZA&CTzAZCACTG;AAGGWCGTCTGTT CTTTCArCGGTTAA, CAAAAPGACA.ATCCTTTTGTTTTTAACACTGCTAAGTTAAA -AGGAATTTACCAA TCGTT GAATTG AAAAAA,30,tV~ C-ACACGTAPCAACGGITTCT CTGGCiTG.TTC-AAAG CAiGT 'CCAGr.TTAA ATCACTCTGCCATUOGT'AACAA %CCPAAGGTGTTGTTA,'A.GATCCTCACATTTATCCAAAGATACTGAACl 5 AAA;CCACAAGTAGATAAGAACTTTGCAGATAAAGATCITTGATTATACTGACAACCAAAAGACAAAGGTGTT G T GC TCAG C GA C A G T T GGOT GA CPA GAA T AC eAT A GT T G GA?-JAAAT T C T TAPG G CTC A GAC TA T PPA A'.ACTGGTTTGGA.CTGA4TAG,/CATGACTPAGGTTGACGTTCACAAC.zACTTA.AG-TAACATTGGATGGT GAAGATTTTCCTGTTTTPAATACAACTCGTACAGATGACCAA- GTTTCGTCTTGCTTGAATGCAA pCA GGTGTTGCAGCAGTAGCttGCAGCTGCAAAA.GACAAAC ATGT-TGAAATCAAGATCA CTTA-TCA CTDCGGTG AA CGGC-TOCACTAC.TGTTGAATTCGAAACCATGATGTTAAjATTGGCTATGGTAATACCCAACGGAA 15 GAAkAG'CGAACCACAAGAAGGTACTCCAGCTAA 6CCA.AGAATTAAAkGTCATTAAkAGACTGGGCAGTAGATGGT ACAAT TACTGATGCTAATGTTGCAGT £AAA34-GCTATC-TTT-ACCTTGC-AAGAAAAC;AACGGAT-GGTA~lCAT GG GTGAACGTTGCTTCACACGAAGCAA-'CA?'sSACCATCkCGCTTTG" ACATACTTTCAPCAGGTTT4GG TAAlTGCT AAACTTACCOCGTTGTCGA.ACGTGTTAGCGGCTACAGTCCAGMJTACGTA.zTCATTTAAAAuATGGTGmTT ACTATC-PAAGAGR-AACTC ATGAT-CAACTCCA.ATCAACCATCGA ACCA AGTGTGA2CTTAT 20 GOGA C G T T T TT G AOA AT C GTA AC AC TG A AC GC TT G GCA GAG CT ACT T C CT CG T TA AG Aa GOAAG G CJATAC TT G GCAC GT A A.s.G CAGGT G CAG CAA CTG C TGAAG C AAAG G CA GCT G T AAACT G CTAAA CTACA~TTGGAT4GAA GCTGTTAAA GCT TATAACGACTTGACTA4AAGZAAAA ACAGAAGGCCZAG.rAAGGTPAA ACAGCAT T GGCWACTG T TATCAAAA ACAAAMOGCtTTACAAT GACCT T T TG TT lVAGCTAAC z TACATAT GAA3 TGGGTTGCAGATAA2AAGGCTGATAATOTTGTcrAAATTGATCTCTA2CGCCGGTGGTCAATTGAAA TT 25 AC GG7TTGGATXGAGCACTTATGGCTTGGAAGAAACTA'AGCA,-CA CAGTTATCGACATTGTCAGGT GA TGTAkACTTTC1AAGCTAkACTGCCAC-ATCATATAGCAkAAGGGCCTACAAC.TGACATCGCATATATAAAIGC T CT GTAAA2AAAAGAT GC CCAACAAG TTCAkCAAAAAVAGTAAC CAT CC CAC.A AACAG GT G GTAT TGG TAC A AWTTCTTTTCACXPSTTATTGGTTTAAQCATTATGCTTGGAGCAG7TAGTTAT CATSAAAAAA PCQTCA TCAG7AG GAAGCTTA.A 30 oar amiuno acid seaucence (SEQ ID NO. 11B); IKK1NRCLTMFSTLLLI LTSLFSVAPAFADDA.TTDTVTLRKIVNTPQAAFON -FTGTKONDSYVGKQIN.DL KSYFG rSTDANE IKO AFE-VEA-NETGTKFI TENGKEVDTLEAKDAEGAV:LSGLTKDNGFV1FNTAKLK3 IYQ1V ELI<EKSNYDIU4CS 5 LADSKAkVPVK ITLPLVNNQCVVKDAH V PKNTETE PQVDKNF'ADKDLDYTDNRKDKGV VSATVGDRKEY IVGTKI LR(SDYKKLVWTmDSMTEGLTFNNW$',KVT.LDG EDFPVLN,%Y JVTDDQGFRLALNAT 35 C-LAAVAAAAK D: . IF RI TYSATVNGSTT VE I PETNDVKLDYGNN PTEES EPQEGT-PANQE1I KVI KD)WAVDG TI TO.AV~tRI FTLQEKQTL TWV.NVASNEAzTKPSRFEHTF'TGLDNAKTYV',VEVSV TPEYVSFKNGVV" TIKNNKNSNDPTPI NP SEPKVVATYSRKF7KTNQANTERLAGATFLVRKEGKYL.ARKAGAnATAEAK.AAVKTAK LA'L DEAVKAtYNDLTKEKQEGQEGKTAI.ATVDQ .QKA'-YNDAFVP.KAWL SYE WVADKKAD-VIVKLI SUAGGQFE I TGIAAGTYGLEETQAPAGYATLSODVNFEVTATSYSKGATTDIAYDKGSVKKDA.7QQVQNKKVaT1PQTGQIGT 40 ILFTI IGLSIMNLG AV VIM KKRQSEEA Strain 1C363 ORE DNA sequence (SEQ I1D NOW 161) ATGA.A -AGAA-TCAACAAA2TA %TTT-TGCAAT-GTTCTCGGCATTGrTTACTG3AC'TT-TAACGTCATTGCTCTCAGTT 45 GC-ACCAGCGTTTGCGG ATGAAGCAACAACTAATACAGTGACTTTIGCPAAOATTTT-GCAAACC'-GAATCAAAT CTTAACY-A lGTA2CTTCCAQACTACAGGTITTA-CGGA.;AGAOCTP~AAGGTGGAGCTATTTCTGA -C CITT 'TGGTTACTTTGGCOGCGGATCTAAtAGAAATCGALAGGTGCGTTCTTTCCTTTAGCTTTGAAA(AGAC T AA AAGTGGTAAA.GTGCAATATGTAGCAAAGTAAATAACGCTJTAAAA GCSTACTCCTGA-AlATAAC, -AGTAA-ZATATTG'ATCGA.GG CC-GTGTCTOCATITGCACCAGAGGGAGATAkCT3GACTT s0 OTTTTCAACA CACGATTGAPAGGCGAC-TTTAAAATTGTTGA'AGTTAAA24TCAAAATCTACTTACAACA.AT A;ATGGTTCCCTCCTGGCTGCTTCAtrAACCGTTCCAiGTTAA;4CATCACTCTTCCATXTGGTAAA PTGAA7ATGGT GTTGTTGCTCATGCCCATGTT TATCCAAAGAr.2ACACTCAAGAAAACCAAA.TTGATk.AAAlACTTTCCTPAAA ACAACGATTTOACAGCAITTOCAC ATGTTAATAGCAC TT TGA,7CAGCTGGCGCA AATTATGCTPATTA7 TGCAZ CGTGACPAAACCAACTGCTACTGCTGAA.ATCGGTAAAGTTGTTCCTTATGAA %GTTAA-PAC.AMJAkTTC~AAA 3.5 CGTTCTAAIATACCAAA,-ACTTGGTTTGGACAGATATAATGTCAA ATGCTTTGACAAT-GGOTTCAACTT AGcC CTTAAAGCTTCAkGAACTACAGAAACTTTTGCTAA 1C-GATACAG7ACTATGAACTTAGCAPTTGATGCCCGTCGT TTCACATTAAAATTCACAGCTGATCGATTGG GCAAkATTGCAAAAQCAGCTAAA,-ACAQCTQ;'ATATTGA ATTT ACATTG7ACTTATA GTGC TACTGTTAATG GTCAAGCAATTATTGATALATCCACAGATCCA.ATGATATCAAATTG TCGTATGCTAACAAZACCA, GGTAMA.GACTTCACTGAACTTCCrTGTTACACCTT4CAACCGTGAAGTAACAGTT 60 CC-TAAAAUCTTGTCTG.ACGATSCACTATGTITAAGTTTTTAACCACCT"AAAiA'AA AOWG-TTGOTTOAGTnTCATTGACAAAA.ACATCThAAGGTAC'AATCGACCTTGG AAAT-IGGTnTCAATT TGAA GTATOTGGTAACTTCTCGGGTA,'ATTCACT'GGTQTAGAJ.ACAPATC-ATACA4GATCTCAGAAC-GTGTTTC2 GGTTAOVGGAulGWGCAATAPA 'TCTAGA~tAAWGGTAAAGTAAOOr-AT TACCAATA CC .AAATTCTGI,-ATAAICC CA ACACCATTGAACCCAAqCTGAAC-CAA, AAGTWGA AACTCATGGTAACAAA-5 sTWT'GTQA.AACTAATG;AOAA-GGT 5 GACCGTTTGGCtrGGTGCACAA TTCGTTGTGAAAVACTCAGCA.GTAATACCTGO;TOTTAAGOiAGATCAAt TCnGAAGGTCAAAAAAil. CTTTAGCTGCTAAGAAATAG(CTTTAGATVGAAGC TATCGCTGcT'rATAACAAGTTG TCTGCAA. AGACCAAA,%AAGGWGAA AAA2%GGAA.TTACWTGCAAAA&.SAACTTATCAAAACTAAACAAGCAGATTAF C G7ATGCAG CCTTCATTGAGGCTCGTACAGCTTATGAGTGG7ATAI2AGA.TAAGGCTAGAGCCATTACCTACAQT TCAAAQG -- ATOAAGG-TCAATTTGzAAnGTTACA'.GGTC-TTGzCAGACGGTACTTACAAkCCTTGAAAACACTTGCT 10 CCAGCAGG-ATTTGCTAAGTTGO CAGGTAATAiTTAAG TTTGTAGTTAATO-AAGGGTCATACATAPACAG GTGT .AOATTGACTACGTTGCTAACAGC nAAAAkAGATGOGAOAC^GTGTAG>AAAA.TAAAAGGTAnACAATCCCA CAAACGTGGTATTGG ACAATTOTTTTCACAATTATTGGTTTAAGCATWAT GCTTGGAGCAGTAGTTATC ATGAAA-AGACGCCAATCAAAGGAAGCTTAA l ORE aminio acid sequence fSEQ ID~ NO, 119): 15 NRRtNR:t~YFAN.FSALLLTLTSLLSVAPAFADEnATTNTVTnLfflULQTESNIJNKSNFP.21 TTGLNGKDYKGG-AI SD LAGYFGEG~tS RE ISGCAFFALALKE DKSGKVQYVKAKPRGN LT PALI 14KDGTPE I TVN I DEA~VSGLTPEG DT-GL VFNTKGLKGEFRIVEVKSKSTYNNNGSTLA.ASKA'rVVKITLPLV7NEDGWADA~IWYPKNTESKPEI DKNFAK TNDLTALTDVNiRLLTAGANiYGNYARDKATASTAEIGKVIVPYEVKTKI-IKGSKYENL WvTDIMSNGLTMGSTVS LRASGTI'ETFAKFDTDYEISIDARG 'TL .FTADGL& EKAF.,AKTADT'IEFTLTYSATVNGQAI IDNE-ESND2I % 20 SYGNKPGKDLTELPVT PSZGEVTVIAKTWSDGIAPDGV 'NVV7YTLKDKDKTV 1ASVSLTKT SKGTI DLGNGI EFE VSGNFSGKFWOLENSSYMI SER kSGYGSAI NLENOKVTTITNTKDSDN FTFLNPTEP VJETHGKKFVK<TNEQIG DRLAGAQE-%VWNS-AGKYLALK.ADQSEG-QKTL,.AKIYIDEATA.AYNKLSATDQKI'CITAKELTKT} .QADY DAAFIEARTAYEW ITDKARAI TYTSNDQGO FE VTGLADGTYNLEZETLAPAGFAELAG NlI KFVVN!,QGSY ITG NI DYVANSNQKDATRVENKKVT IPQTGOG TT 1 T I ILS IMLGAVVT-,;MKRRQSKEA ORF DNA setguence (SEQ ID NO: 162): A TGAA,ATCAACAAATATTTTCATCTTCTCGCATTGTAI CTACCGTAACATOCATTGTTCTCAGTT GCAGACAGTGTTTGGGGA.AGA.AGO~ AATACTGACACAGTGACCTTGCA-CA~AA"TGTCATGCQCTCGAA;CT 30 GCA-zTTTGACGGTTTTACTZGGTGGTACAAAGGGTAA,2GGA TAA TACTGACTACGTTGGTAA3CAAsTCGAAA OTTAJLAA-CTTAGTTTGGCTOAGGCGAAGC^GAA AP.A'ATCOAGGTGGTTACTTTGCTTTAAAAVTGAC-T OG(TAO',TAAAZTACA TCACT'GA.AAzATGGT GAAGAAGT TGATACTTTGG ATAGAACAGATGOO'CAAAGG;TT-GTGO .T GTTCTTAAAGG TTT. JYOAACAGACAAT - GGTTTCAAA'TTTACACTTCTAAAl-TTAAGAGGAAGTTACCAAATC GTTGAlATTGAAAG,;P,PAJ 1 ATGTACA'.TACAVCACGATGGTWGTATCTTGGCTGATTCAA.,AAGCAGCTTGOAGTT 35 AA-AATCACTCTTC-CATTGGTAA2ACGACAATGGTGTTGTTAAAGACGCTCACGTTTATCAPAAGAACACTGAA' ACAAGCCAGAGA-AC TT C;OCAGAT AAA GAAQ T TGAT TATGGAXACAAAAAAAGACAPAGG G ACTGTCTCA.GCATCTGTTGGTG3ATGTTAAAIAATA.CCATGT TGGAACAAAAA.TGO'TT AAAG.ikGTTCAAC(TAkT AAGAAATTAATCTGGACCGATAGCATGACCAAPAGGTT K'GACTTTCAACAAGGrATATTGCTGTAACATTGGAX GGTGGA .,ACTCTTG7ATGC'-TACAAAPTTAPCAAACTTGTAGCAGATGACCAAGGTTTCCGCICTTGTC-TTGACTGAC 40 AAA GGTCTTGAAGCAGTGGCAAA4-AGGGGCAAAAA4CAAAP-AGATGTTGAATCA-AGATGACITTACTGCAGGTACT TTGAACGGTTCTG CTGTCGTTG( AAG TTC4AA AACClATGATGITAATTGGATA-G CAAAAGOCCAAGA A TTGAA.AAT GAACCAAAAGAAGG TAT TC CAG TT GATAA GAAAATGAOPCTGT TAA-CAJAACAT GG'GC AG TAGAT (SGCAA TGAAsGTOAATAAAG CAGAT G AACAGT TGAT GC TG TC:TTOrAG-T TG CAAG TTAAAGA TGG T GACAA TGGGTGAA TGTTGATTCAG CTKA-;AGCAACAGCTG CA'ACTAGC TTCAAAPCAO-ACTTTTGAAA.tG.TTGGA'AA 45 GCTMJ..ACTTACCGGGTTATCGA.ACGTGTTAGCGGCTACGCTCCAGAATAOCGTCTICATTTG3TA.AAT.GGCGTTr C-TAA"CCATCAAGRACAAAAGACTCAAATGAGCCAACTCGA.ATCAACCCAT CAGAAGACIAAAAGTGGTGACT TATGGAGGT-TTTT'AAtACAAtAY tGATGGAAG,CAAGCTTGGCAGGAGTACTTCCTTGTTAAOX AAGATGGCAAG TACTTGGCACGTAAATCAGGTGTTGCA4ACAGATGOAGAlAAAGGTGGTGTAGAtTTCAAOT S'AA.TCAGGATTGGATGC TGCTO4-T TAAGCTT)'LAAATGATT TGASA-~vAACAAAA7AAGAAGGTCAAGCATGGT 50 AAATCA2IGCATTGGCTAICGGTTAGTG,3AAMAG$AXAAAGGTTACA2ATGATGCCT TTGTTA',GCTAACTACTCA TACGGAATGGGTTGAA GATZAAAATGGTAAGAATGTTGTTAAATTATTTTACAThAAAaGTCAATTTGA ATTACTGGCTTGAGTGAAGGTGAA.TAGTCATTCGAA3AAAnCAAGOACCAAG(TGGTTATGCTAAA.TTATCA GGTGATGTTTC-GTTTA'PATGTTA ATGCTACTTATA-AGTAAAGGTTGTGCTCAAGZATATTGAGTATACCGA~I GGTTCTAAAAC, TAAAG.rATG Cx'rACAAAGTTATCAATAAGAAGGTTA CTAzTTCCA CAAACsf-AGGTGGTATT4GGTI 55 ACsAAT TTTTTTCACAAT TAT KGGjATTAAGTATTATGC TTGGAGCGGTAOT-rTATCAiTGAAAAGnQGTcAkTGAp GAGGAAG,-TTTAA ORE amino acid seqfuence (SEQ ID NO; 120)t LKTYFGSGEAKSIAGAV ,FAFKtNEAGTKYITENGEEVDLDTTDAKGCA LKGLTTDGFKN'rSKIvTGTYQI, 60 VSLKEXSTYNNDGST I. LM DS.KP,5,VI TLPI;VNDNGP.C-VVKDAH,.VYPKNTETKPQVD)KNFt AKELDYANNKKDKC- -99 TVSASVGDVRYEiGWK I LKGS YKKL, IWTDSE4TEGLT FNIJDI' AVTI;DGA7,TLDTYLADGRVT KGLEAVARA AKT: tvt I{I TYSATLZJGSAlVLETNDV' KLDYGUN24TIENPEEI PVDIKITlVNKTNAVD GNEVNKADETVDAVIFTLQVKDGDKWV7NVDSAIAT5ATSFEHiTFEN4LDUAKTYRVI ERV1SG YAPEYVSF-VNIGV. VT IENNKDSNE PTINPSE PWA7'YGRKFV7KTNKDGKERLAGATFLVEEDGKYLARNSGV ATZDA-EKAAV DST 5 KSALDA.AVKAYNDLTKEI QEGQDGKSALATVSE{QKAYNDAFVIKANYS-YEWV EDKNANVV7KL I SN11DKGQFE ITGLTEGQYSLEETQAL'T GYAKLSGDVSFlIVNATSYSKGSnQDIEYT QGKTKDAQQVIN %KVTIFQTGQIG TIFFTI IGLSINLGAVVI,7'MERRQSEEV Strain =637 to ORE DNA aeguence (SEQ ID NO- 163). GCAGCAGCGTTT GCGGACGACGCAPACAAPCTGATACTGTGACC-TTGCACA-.2AGATTGTCATGCCACMAGCTGCA TTTGATAACTTTACTGM- GGTACAAA ,zGGTAAGAA',TGATAGCGZATTAIGTTGGTAAACAAAiTTAA ,TGACCTT AAA',TCTTATTTTGGCTCAPACCGATGCTAAAG.;AAATCAA GGGTGCTTTCTTTGTTTT"CAML.PATGAAkACTGGT Is ACAAAA TTCATTACTGA? AATGGTMAGGAAGTCGATACTTTGGAztCTAAAGATGCTGA-AGGTGGTGCTGTT CTTTCAGGGTTAA.CAAAAGkACAATGGTTTTGTTTTTAAC.ACTGCTAAGTTAAAGAATTTACCXAATCGTT GzAATTGAAA sGAAAALATCAAAG-TACGzATAACAACGGTTCTA34TCTTGGCTGnTTCAAAAGCAGTT-CLITTA A ATCACTCTGCCAkTTQGTAAA CA'ACCAA GGTO'TTGTTA'AAGATGCTCAi'CATTTATCCAAGA ATACTGAAA; CA 20 GTCT,-CCGAC -AGTTGGTGZCACAAAAA"AGAATA2CATAGTTGGAACAAAA.ATTCTTA2-hA GGC-TCAGACTATAAG AXAV-CTGGTTTGGACTGATAGCATOACTIAAGGTTTO-ACGTTCPA JPACAA CGTTAAAj'GTAACATTGGATGC-T (3A.'AGATTTTCCT''.GTITTAA.AGTACAAkACTCGTAACAG ATGAkCCiAGGTTTCCGTYCTTGCC"TTOAATOCACA C" CGTCTTG-CAGCAiGTAGrCAGCAGC-TGCAPeJSAOGACIL'aPGATGTTGAAATCAAGATCACTT ACTCAGCTACGTG AAC-GGC T CCA CTAC T GTTGAA1A TCCi-AGAAAC C AAT'GA TGT T AATTG GAC TA TGGT AATAAC CCAATGGAA 25 AAAGT.ZAACA.CAAGAAGGTACTCCAGCTAA2CCAkAGAAATTAAAQ TCATTAAAGACTGGGG.-AGTAkGATGGz(T ACA'ATTA'CTGATQCTAATGTTGA.TTAAA'CTATCTTTACCTTGAAAAAAACA~AACGGATGGTA-ATGG GTGAACGrTTGC'TTCACACG5AAGCAACAAAACCATCACGCTTTGAA-CATACTT-TCACAGQ-TTTGGAITAA-TGCT IJ-,iAPCTTCCGCGTTGTCGACGTGTTAGCGCTC-ACTCCAGAATAC-GTATCATTTAAArATGGTGTTGTG RO-TCAA2GAAG.AACPLAJAACTCATGTCOAAOTCOAkATCAkACCCATCAGAAOOAAAGTGGTGACTTAT 30 GGACGTAAATTTGTGAA ACA.AATCAPAGCTAACACWGPACGCTTGGCAGGrAGCTACOTTCCTC-GTTAAGAA GAkAGGOAA,7 CTTGGACGTAAGCAGTGCACACTOTGAAGCAAGGCAGCTGTAAAXACTCTAAA" CTAGCATTGGATGAAGCTGTTAA.GCT1TATnACGAGTTGACTA -RCA ZLMA-CAnAGQCGfCAAGAAQCGAA-A ACAGCATTGGC-TACTGTTG ATCAr1A.ACA7,AAACTTACAATGACG CTTTTGTTAARAGCTAACTRCTCRTAT GAA TCGGTTCAGATAAARR-LkGCTGATAATGTTGTWAAR-TTQATCTCTAIACCOCCGGTGGTCARiTTTGAAXXTT 35 AC-TGG TTTCCATAAA3 GG CACTTATGCCTTCGcAAG ZAAOTCACACCAGCAGGTTRTGCGA.CATTCTCACGT 1^GT4TATTTQA r.VGTRAsCTGOCACATCATATACAGCGCTACAAICTG" AC GCATATGATAAAiGS'C TCTGTAA.APAAAAG'ATGCCCAtACAA(3.TTCAAAAzCI-AAARMVGTAAQACA TCCCACtAAEICAGGTGGTAVTQGTAcR ATT-CTTTTCACAAVTTATTGvGTTTACGCATTATC-TTG-RCCAGTAGTTTCATRAR;SAACGTCAATCAG GAAGCTTIA 40 ORF aMino acid Secie (S.Q TD N4O- 121): KSYFGSTDAKE TKGAFFVEI{FNETGTKFl TE WGKEVDTLEAKDAEGGAV .LSGLTKDNqGFV ,FNTAKLKGI YQIV ELKEESNYDNNGS I LRDSKRAVFVKITLPLVN :NQGVVPKDANI YPKNTETKPQVDKNF-ADRDLDYTDNRKDKGV VSATVGDKKEY IVOTKI LKGSDYKKL ,VITDStATKGLTF-lNi'h rJTLDGEDFPVLNY JVTDDQGE-Ri-LLNAT 45 GLARAVAAARKDKDVE IKI TY SATVNG ST TVEI PETN DVKLDiGNN PTEES EQEGT ANE IKV I KXAVDG TI-TDRN'VAVK AI TLQEKQTDITWVNVaASHEATKPSRFEHTFTGLDNAK,-TYVERV-SGYTFYVS'KG-VV Tl Kr4NKNSNDPT 2INPSEP-'KVVTYG RKEVKTNQANTERLAGA,-TFLVK:KEGKYLARKA GRAPTAEAK.AVKTAK LALDEAVK7FAYN DLTKEKQEGQEGKTALATVDQKQKAYN-DAFKANYSYEWV7ADKKADOJ'VVKLI StIAGLGQFEI TGLDKGTYGLEETQAPAC YATLSGDV}WIEVTZT SYSKGA' TTDIAYDKGSVKKDA QQV QNEKV-nT IPQTGGIG-T 50) ILFTIIGLSIMLGAVVI I1MKEQSEEA ______ Strain 1C377 2LZ2AIAeanc (SQ ID NO. 164) ATGAA.DAAAAATCAAkCAARTCTC(.TTACAA T'GTTCTCGC7. CACTG,-CT4ATTGATCT"-TA. £2GTCAJTATTCT-AGTT 55 CCCCAGCO-TTTGCGGACGA CGCAACAA24CTGATRCTG;TGACC TT(CCAC.AL;TTGW'CATGCCACAAG7CTGCA TTTG - ATRCTTTACTGAGGTACAA,'AAGG TAAGAATGATAGCGATTATGTITGGTAACAAATTARTGRCCTT AAA"TCTTATTTTGGCTCAACCGRTGCT4AAG ~AAATC-AAGGoGTGCTTTCTTTGTTTT- AAARTGAAACTGGT RCAAAR; TTCATTACTGArAATGGTAAGGAA %GTCGATAOTTTGGAAGCTA'AAGATGCTGAA.PGGTGG TGCSGTT C T T TAG GG TTALACAKAGAtCAAT GGT T TTGT T TT TAACAC-T G CTAAGTARAAGGAAT TTAC CAAAG T T 60 GAAT T GAA.AGAAAART CRAzCAGTCGRTAACAAC GG TTC TAT CT T GGC TGAT TCAIUAGCAGT T CCA-T TAA - 100 ATCA;%CTCTGCCATTGGTAA ACAA CCAAGGTIGTTGT TAAAGATGCTCACATT TATCCA?4AGAATACTGAAACA A.AACC A CAAQT AGAT AGAACTTGAAGTTGTACTAACGAGCAG T GTCTCAGC-GACAGTTGGTGACA&AA.AAGA7 ATACATAGTTGGAkAC3AA.AATTCTTA-AAG;GCTCAGACTA.TA.AGr ?-kAQTGTTTGACTCTAGCAT-ACTA.GAGTTGACGTTCACAACACGTTAA' T-AACATTCGrATGGT 5 GACA6A tTTCCTGTTTTAACTACAQr4TCGTAACAGATACCAiAGGTTTCCGTCTTGCCTTGATGCAACA GGTCTTGCAGCAGTAGCnCGCAGTGC-AAGACAAAGATGTTGAAATCAAGATCACLTACTCAG CTACGGTG AACGGC-TCCACTAC TC-TTGAAATTCC'AGAA;ACCAATG ATGTTAAA4TTGQ'ACTATGGTAATAACC-CAACGGAA G7 AAGCTGAAJCCACAAZGAAkGGTACTCCAGCT AACCAAQA.AT TAAAGTCAXTAAAGAC TGGQCAGTAGATGGT ACAATT ACTCATGCTAATGTTGCAG TTAAAGC TATCW-TT CTGAGAACACGTGAAT GG 10 GTQAAICGTTGiCTTCACAGGCAAGC-jAACAAAiACCATCA2GCTTTGP.AiCATACTI'TCACAGTTTGGATAA TGC T AAAACTTACCGCGTTGTGAACOTGTTAGCGGCTACAGT-CCAGAkATACGTATCATTTAAAZATG GTGTTGTGv AC TATCAAGAACAACAPalC T CAA ATGAT CC AAG TCCAATCAAC CCATAGA-CAAAGTGG TGAC TTAT GG-AGTAATGTGAAAAik~CAAA~iTCAiGOT~AACTGAAGGT T(GAGAGC TACTTCCTCGTTAAGAAA G AAGGCAAATACTTGGGACGTAAAz C-CAGG TGCAGCAACTGCTGAA4-GCAAA GGCAGGTG TAAAAPACTGCTAAA 15 GTAGcAT TGGATG 1 uAGTGTT;AAGCT TATklrGNC.T TGAOTAAAAGJGGcAAGTA AC-AGCATTGGCTAOTGTTGATCAPkAAAAAUAAktGOTAGAA.TGACGCTTTTGTTAkAAGCTAAG.TAGTCATAT G-AA TGOGTTGCAGATAAjlAAA-GGGTG-ATAATOTTG;TTAATATTGATCTCTA ACGCC-GGTGGTCAATTTGAAA42TT A CTGGTTTGGATAJ\GACGCA'CTTA'TGGGTTGGAtAC AACTCAGCACCAGGAGGTTATGCGACA TTGTGAG3GT G ATGTAAAGTTT GAAGTAAGTGC-CACATCATATAGGA.AAGGGGTACAACTGACA.rTCGCATATGATAA,,GGG 20 TC-TGTA AAAAAkGATGCC'AACA-AGTTCAA %AAC7-AAAAAGTAACCATGCCAC-AAAGAGGTGGTATTGGTAGA ATTGTTTTGAGAATTAkTTGGTTTAkAGOATTATGGTWGGAGOAGTAGTTATCnTGAkAAA. AGTCAATGAGAG CGAAGOTTAA OR? a-mino acid senuenc (SEQ IDn~ 122) 25 KSYFG S&DARE I KGAFFVFKNETGTKFI TENGEEVDTLEAKDAEGGA2'VLSGLTKDNGFVFNTARL KG1 YQ IV VSATVGDKKEY 1V GTKI LKGSDYKKLVWnTDSMTKGLT'N TTJVCTLDGEV)FPVL"NYKdVTDDQGFRLALNfAT GLAAVI~aAAAKDKDVE IKITYSAT'VN-GSTTVEI PETNDVIKLDYGNNPTEESE -PQEGTPANQeE1 EVI KDWA.VDG TI TDA.NVAVKAI FTLQEKQTD-GTWVNV-,ASHEATKPS9RFEHTFTGLDU.AKTYRWvERV SGTPEYVSFKNGVVP 30 TI KNNKNSNDPWPI NPSEPKV VTYGRKFVK' TNQANTERLAGATFLV' KKEOKYLARKAGPAATAE7AKPAVKTAK LAIDEiAV.KAYND4-'LTREI QEG(QEQKTAL AT-VD)Q}QKAYND.-AFJKANVY SYEWVnOKKADVIL I SNMIAGOQrz I TGLDKGTYGIAEETQAPAGYA& LSGDV;NFEVTATSYSROzATTDIAYDKGSVKKDAQ-QVQNKKVTI PQTGGIGT ILETI lGtS ItLG AVVIMKKRQSBEA 35 Strain 1C379 OR? DNA sequence (SEQ "' D NO: 165): A-TGAAAA AATCAACAAADTGT-CTTACAATG;TTCTCG7-ACA,''CTOTTTGATC'-TTAAC'(-C-ACTATTCTAGTT GCACCAG CGTIYTGCGGACGACGC AACTGATACrTGT-GA'CCITTGC'AGA3AGATTGTC-ATGCCACAAG( CTGOA T TTG-'ATAAkCTTTAGTGAArGGTA ,C AAAGGTAAGAATYGATA',3GGATTAICT TGIVAkATTAATGAccTT 40 ;-'ATQ-TTATTTTG GCTCACOGATGCTAPG.-ATOAAGGGTGCTTTCTTTGTTTTA-AAATGAA-CTGGT ACAAJAATTOATTACTGAA)TGGTAGGAGTCGATATTTGGAG CTAAGATGCTG7aJ400TGGTGCTGTT OTITOAGGGTTAACAsAAGA-AMTG-GTTTTGTT, TTAtICAO GOTnAGTTAAkAAGGAA.TTTAOOAA.TCTT G77ATTGAPAGA.Z'AAzATC.AA-ACTAO~rGAT?.ACAIACGG,'TTCTATCITTGGC-TGATTCAAAA-UGGAGTTCCAG(TTh'AA ATOAGTQTGGCATTGGTAACAA-kCAGTGTTG'TTAtAAGATGCTO"AGATTTATCGAA1AG.AATACTGAAAGA2% 45 AAACC-ACAAGTAGAT7AAGAACTTTGCAGATAAAGA 3ACTTGATTATAGTGAC-AACCGAAAMGAC-AAGGTGTT GTGTCAGCGAGAGTTGGTG ACAA.A.lAAGAATACATAG TTGGAACAAAA-;AT ICTTAAAGGCTCAGACTATAAG ,AAGTGGTTTGGACTGATAGGATGAGTA AAGGTTTG'AOGTTOA.AGACAAO GTTiAAGTAAGATTQOATOQT G7AAG.-ATTTTCC-TGTTThA ATCAYAG-TCGTtAGrAGATGAO.CAAGGTTTCCGTCTTGGCTTG AATG-CAAOA GWTOO GCGCAGTAG CAGGAGCTGGPWGACAASOATGTTGAA ATG -AGATGAOTTAGTCAGCTAOGGTG 50 AAICGG CTCCAC-TAC :G'TGAAATTCCAGA AACCAATG ATGTTAAA TTGGAO'TATGGTAATA.ACOGAAC-GGAA GAAGTGAACAAAGAAGT-ATCAOTACAGAAATTAA'GTATTAAC-ACTG'GGCAGTAGATGG T ACAATTAO-TGATGCTA24ATGTT-GCAGTTAA-AGGTATG'-TTTACCTTGCAAGAAkfAAAMGGGATGGTACA5TGG GTGCG'TTGOTTCAC-ACGAAz'GCAAiCAAAeACGATCACGGrTTTGAACATAGTTTCACAGGTTT aGATAATGGT PA%AGTTACCGCGTTGTCGAAOCGTGTTAGCGGGTAG,,ACTOOAGA',ATACTATCATTTAAAAATGC-TGTTGTG 55 .CTATCA.AC-AACAACAAAAOrCTCAAATGA TCCA 4AGTOATCAACGCATCAGAACCAAAGTGGTGAGT TAT GGA 'CGT 'AATTTGTGAAMCAAPATGAAGCTAAzCACTGA,'ACGCTTGOOAGGAG JTAG JTCCT-GTTAAPGAAA; GAzAGGCAAzATACTTGGOAOGT&AAC.CAGGTGOAkGCAAGTGCTGA-AG -CAAAGGCAG7CTGTAAAAAG(TGCTAAAu CTAGATTGGATcSAAGGCTGTTAAAGCTTATAACGA6CT L'GACTAAAGAA.AAAAAAGGCCAAGAAGGTAAA ACAGGATTGGCTACTGTTG.ATC.AAAACAAA 1AAGGTTACAATGACGCTTTTGTTA7 AAGOTAACTACTCATA-T 60 GAA' TGGGTTGC'-AGATAA.AAAGGCTGATAATGT ,TGTT-i')A TGATCTCTAACGGCGGTGGTGAATTTGAAATT IAC2GGTTTGGA, T~zAGGC-ACTTA2TGGVCTTGG-AAGAAATC:CAA GCACCAGCG GTTT-GCA CAfTGTCACGT TC-TGTAAAWAAGATGCCC-A.ACAACTTCAAA-AAAAAGTA ACCATCrCCAC-AAACAGGTGGTATTGOzTACA ATTCTTTWACAATTATTGGTTTACATTATGTTGGAGCAGTASTTATCTGA AAA.ACGTCAATCAGAG 5 GAAG-CTTAA ORE amino apid sexaence (SZO ID NO: 123) MEKIN tTCLTNFSTLLLI LTSLFSVAPAFADDATTDTVTLHKIVMPOAAEDNFTEGTKGKNDSDYvGKQ XNDL, ESY EGSTDAKE I IGAFFVFKNETGTKFITENGKSVDTLEAKDAEGGAV.LSGLTKDN4GFV FNT AKLKGI YQIV~ ELKEKSNYDNNGS ILADSd-tAVPVK ITLPLVN-NQGVVKDAH 1- YPKN4TETKPQVDKNFADKDLDYTDN4RKDKGV 0VSATVGDKKEYIVGTKI LKGSDYKKL tITDSMTKGUTFNNNVNVTLDGEDFPVLNv YKLTDDQGFRLLNAT GLA"AVA,"AAAKDIDEIKI TYSATVNGSTTVEI PETNDVKLDYGNNPTEESEPQEGTPANQ^-EIhVIKDWAVDG T XTO~aNVAVEAl FTLQEKOT L*TvNNASHEArK2SRFEHT kONLl AKTYRWSREVSG YTPEYVSFKNGVV. TIKtJ4KNSNDTPINPSEPVVTYGRKVKTNQATERLrGATFLVKKEGKYLARAGAATAEA'AV K AK LALDEAVKAY NDLTXEKQEGQEGKTALVYVDOKQKYN DAFVKAN YSYEWWADKKADT4VVKL ISNAGGQFEXI .5 GLDKGI YGLEET.APAGYATLSGDVN'tFEVT.ATSY SKGATTDIAIDG SK 4KDAQQVQNKX I TI PQTGGI T ILETI IGLSIHLGAVTVIMXKRQSEEA Strain IC432 ORE DNA sequence (SEQ ID NC- 166) 201 ATSA)%.AAAA.ATCAAkCAAATGTCITACAA %TGTTCTCGACACTCTATTGATCTTAAC.3TCIACTATTCTC.,A.GTT GCACCAGCGTTTGCGGACGAO-GCArACAAOTGATACTGTGACCITTSCAtCAAG ATTGTC-ATGCCACAAGCTGCA TTTG ATAACTTTAC m G AAG GTAC'AAAAGGTA AGAATGA TAGCGATTATGTTGC-TAAAOAAA TTAATCACCTT AATCTTATTTTGGCTCAACOGATGCTAAAY GAAATCAAGGGTGOTTTCTTTGTTTTAALA TGAAGTGGT ACP-A.AATTCAZTTACTSAAAGTAAGAGTC2ATACTTTGAAGCTAAGATGCTGA,'GGTGGTGCTGTT 25 C TTTQ-AGGO-TTAACPJuzAGACAAiTGGTT TTGTT TTTA-CAOTGCTAAGTTAAAAVGGAAi %T TTAQC CAAA.TCGTT GAkATTGAAPGA. eIkTCAACTAC AAA.CA CGTTCTATCTS-'GC-TGATTCATAAG-AGTTCAGTCTA p' ATCACTCTGCCATTGGTAAALTCAACCAAGGTGTTG TTAAAj GATGCTCAC .TTTATCCAAA~iGAA TAC'TGAAkACA GTGTO-AGCGAC-AGTTGGTGAOAAAA-tAGAAlTACATAGTTGGAACAATAATTCTT AA5JGGOTCAG 1 &,CTATAAG GAAG,~rATTTTCCTGT TTAAACTP AAATCGTAACAGATGACAAGGTT TCCGTO-TTGO-CTTOAATGCAACA.f" GGTCTTGCAS' CAGTAGOCAGCAS'CTSCAA AAGACAAAG CATGTTGAAXATC:AAGATCACTTA'CTCAGCCTthCGGTG AACGGCTCCACTACTGTTG2AAA %TTCCAG3AAACCAATGATGTTAAATTGGAC',TATGGTPATAA'CCAACGG AA GAAAGTGSAACCACAAGJAAtGGT ACTCCAGCTAACC-AAG AAATTAAGTCATTAAAGAC'-TGGG-CAGiTAGATGGT 35 ACAA7lTTnCTGATGCTAAkTGTTGcCAGTTAAGCTATCTT -TACCTTG CAAGC AAAACAU.AOGGATGG;TAATG GTGAACGTTGCTTCAG-ACGAAGCAACAAAACCA CACGCTTTGAAO-ATACTTTCACAGGT TGGATAAT 7GC-T AAAACTTACCOCGTTGTCGA ACGTGTTAGC GGCTA CACTCCAGAATACGTATC'ATTTAAATGGTGTTGTG AQTATCA-AGAAkCA'ACPIAAAA-CTQAAAt3TSATCOAACTCQAATCAACCCATAAACOAAnAGzCTGG GACT TAT GGACGTAAZATTTOTC4AAA!-zCAA,,%ATCA.AGCTAAC-ACTGAACQCTTN.GCAG3GACTACCTTCCTCTTA %GAAU 40 GAA;UGGCAAYATAC^TTGG-CACGTTAAGCAQ^GTGCAGCAkACTGOTGAAJGCAAAuzGGCAOCTGTAPSIAAACTOCTAAAt CTAGCATTGGSATGAA GCTGTT.AAAGCTTATAACGtCTTGAC.TAAGL A 2 ACtAGf AGGCCAAkGAA GGTA.AA ACAG CATTGGCTACTGTTGATCAA2AAA4C.AAAAAGCTTAOAATGAC GCTT-TTGTTAAAOC ~rTAACTACTC-ATATI G, ATGGGITGC>.G:. TAAAAA~~iGGCrTG. AA.TGTTGTTAAATTGA'TCTCTAAO.GCCGGTGGTCAiATTTGAAAV-TT ACTGGTTTGGATAPACGCACTTA GGCTTCGAAG AAAZCTCAAGCACCAGCAGCGTTATCCGAC-ATTCTCAGGT 45 G ATSTAAA CTTTGAAOTAACTGCOA CATCATATAO-CAAAGGGGCTACAACTGACATOGCATATG7ATAAAGOC :CTGCTAAPAA.AATCCACAAGA TCAAAA4AAAAGACCATCCC~'ACAAACAGTG-,rATLTGGTACA ATT CTTTTCACAATTATTGGTTTAAGCATTATGCTTSGASCIAGTnGTTATCATGAAA AACGTCAA' TO-AGAG GAASCTTAA ORE amino acid leuec (SW1060 124): 50 M1KKINKCLTNFSTLLLI LTSLFSV.APAFADDAkTTDTVTLI:KI VNIPQAAFDNFTEGTXGKNDSDY-VCKQ IINDL KSY FGSTDAkKE IKGAFFVFKNETGTKEI TENGKEVPTLEAKDAEGGA' L SGLT ,DNGTVFN.RTA2KLKGIEQ IV ELKEKSNYDWNGS ILADSKAVPVKl TL2LViNNQG'VVKDAH IYPKNTETKPQVDKNEA.DDLOYTDNRKDKGV VSATVGDK .EYIVG TKILKGSDYKKLVWTDSMTKGLTlNNtVKVT-LDGEDFPVLNY(LVTDOQGFRLAiLN T GIJAAVAAAAKDKOVE I 1 TYSATVNGSTTV I PETNDV IKLDYCNNPTESSEPQEGTPA4QE lEVI DWA VOG 55 ITLANVA t AKAI 'QKTTNNAH KS REEHTFT-GLDNAKTY~rWVRVSGYT PEYVSEKNGWV I ALDEAViKYNDLTEKQEGQEGKTALATVDQ.KQKA YNDAFV-,KAN4YSYEW ADKANVVY',7L I SN:AGGQFE I T GL4DKGTYGLS-ETQA PAG-YATLSG DVNFE:VTATSYSKGA'PTTDAYDKGSVKKDAQVQNEKVTI PQTGGI ST ZLFT I I GLSTIMLGA%',VIMKKRQSEEA 60 -102 Strain 1C455 0R1 DNA seguience (SEQ ID NO: 167) CTGMAAGAATCAACXAtATATTTTGC 4AXTGTTCTCGGCATTGTTACTGACT TTM ACCTCA TTGCTCTCAG,'TT GCACCAGCGTTT GC-GGATGAAGC--PCA2,CTA~aTACAGTGACTTTG-ACAGATTTTGAIAACCGjAATC-AA;AT 5 CTTAACAAiAGTA2,CTTCCCAGGAA~CTACAGGTCTT'ACGAAATIAGACTACMelAGGTGGAGCTATTTCTGAC *CTTGCTGGTT ACTTTGGCCAGGGATCTAAaGAATCGAAGGTGCGTTCTTTGCTTTAGCTTTGA. AGAA2sGAT 5 A)Jd7GGTAAAG CTGCAATATGTTAAGQAAAA GAAGGTAA CAAATTA ACACCAGiCCTTA.A tTAATAAGA-i~T * GTACTCCTGAA.TAACAGTAAATATTGATGAGGCCGTGTCTGGATTGAC(ACCAGIAGGGAGcATACTGGACTT GTTTTCAACAC CA AGGATTGAA-GGCGAGTTTA~lAATTGTTGAAGTTAATCAAl sATCTACTTA'AACAAT 10 AATGGTTCCCTCCTGGCTGCTTCAAAACCGS TTCCA GTTAACATCACTCTTCCATTGG TAAATGA.AGATGGT GTTGTTGC-TGATGCCCAT GTTTATICAAAAACACTGAGAAAAAC -CAGAAkATTGATAAAA7 ACTTTGCTAAA ACAAA %CGATTTGA&AGCATTGAC'-AGATGTTA'ATAGA.CTTTTGACA GCTGCGCA- ATTATGGTAAITTATGCA CGTGA4CMA,34GCAACTGG TACTGCTGAI ATCGGTAA-A GTTGTTCGTTATGA.AGTThAk-AC LMAATTACAAA, GGTTICTAAATA-CA AAACTTGGTTTGGAC-AGATAT'AATGTCAAAl'-TGGTTT GACAATGGGTTCAACTGTTGCC 15 CTT,1AAGCTTCAGGAAC(TACAGAA2ACTTTGCTM.-GGtTACA ACTATGA ACTTAGCATTGATGCCCGTQGT TTCA-CAITAAAAzTT-ACAGCTGAT GATTG- GCAATTGAA-LAG(CAGCTAA AACAG CTGATATTGAA'TT AC'ATTGACTTATAG TG-TACTGT TAATG GTCSAr3C7-k TTATTGATAPATCAGAATCC;'ATGATATCAAATTG GCTA.4AACTTGGTCT"GACGGAA-TTGCAGCTGATGGTGTAA.ACGTTGTTThCACATTGAA.AGATAAMGATAAA 20 ACTQGT TGC TTC A GTAT CAT TrGA C iAAAAC A.TC TAG G T A CAAT CGAC CTT G GAAATGG TA.TCAAkT TTGA GTA'TCT-GGTAACWTCTC-GCGTAAATTC.ACT3(TCTA5A.AAATCAAA,. TC>TAJYAC.TGATCTCAGAkACGTGTTTCT GGTTACGGAAQTGCAATAAATCTAGAA,-AATrGG-,3hAAGTAAC-CAT.TACCAATACC-.2AAGATTCTGATAACCCA ACACCATTC-AACCCAA- CAA CCA AAAG TTGAPLAACTCATG GTAAGAAA-TTTGTCA-AAACTAATGAACAAGG T GACCGTITGGCTDGTGCAkCAA14TT-CGTTGTGA--AACTAGCAGG3TAAA-7TAGCTT-GCTCTTAAAC(-AGATCAA, 25 TC-AGAAGGTCPAAAAAAC-TTTAGCTGCTAAGAAATAG CTTTAG ATGAAGCTATCGCTGCTTATAACAQTTG T C TQCAACA0ACCAAAAVAGG T GPAAAG GAAT TAC T G CAAAAGAiC T TA TC PAAAC TAACAAGC AGAT TAC GAT GCAGCCTTCATTGAG0CT CGTACAGCTT.ATGAkGTGGATAAkCAGATA AGGCT.AGAGCCATTACCTACACT TCPSAUCGATCA AGGTCAATTTGA PAGTTACAGGTCTTGCAGACGGTACTTAC-AACCT TGAAGAA?.C(-ACTTGC-T CCAOCAkGGAlT'T.TGC-,'~TAATTGGCAGGTAAT'ITTAG-TTTGTAGTTAATCIAGGGTCATACTAA~iCAGGGT 30 A C AT T GAC TACG TT G C TACA GCAC CAAAAGAT GC GACAC GT GT A GAAAA,.TAAAPA'iG G T AACAAT CCA CA71AICAG jGTGAT - TGG TACAAT TC TT TTCACAAT TA TTGG T TTAA.GCAT TAT GCT TGGA GCAGPA,"G TTAT C ATGAAA-AGACGCCAATC2 AAGGAAGCTT;A QRF am nno acid av en eQ 5 ID_ N-_125) 35 LAGY FGEGSEE I EGAFFALAL{E DKSGKVQYVI{AKEGNlKLTPALI NKDGT PEI TVNI DEAVSGJT PEG DTGL TNlDLTALTDV.NRLLTAGANYGNYARDKATATA.E IGEVVIPYEFVKTEK I HKG SKYE. LVWTDIMSNGLTMG STVs LK ASGTTET'ARDT DYE LS1IDARGFTLKFTADGLGK LE~kAAKTAD I EFTLTY SATVNGQ I ID Me ESNDI KL SYGN ;FGXDLTELPVT DSKGE-VTVAKTWSDG IAPDGVNVVJYTLKD: DKTVAS1VS LTKTSKt3T iDLGNlG W~ 40 VSGNFSG:KFTGLENKSYMI SERV SGYG SAl NLENGKVTI 1TNTKDSDNFTPLNTE PKV ETE{GKKFVRjTNEQG DPLAGAQ-V-VKNSAGKYLALKA DQSEN3QKTLA'AKKIALDEAIA' AYNKLS-ATDQKGEKGI TAKELIK ETEQADY DAAFI EARTiAYEWI TDKARAI TYTSNDQGQFEVTGLADLGTlYNLEETLAPA&.GFA;KTAG'-N IK1E-,VNQ',GSY I TGG NI DYVANSNQKDATRVENKKVTI1 PQTGG IGT ILFT I IGLS INLGAVTVIN-RRrQS KEA 45 Strain 1C457 DNA sequeane ( SEQ -ID NO: 168) TTTTAT A.TCAAAAAATCACAAAGTTTACAATTTCICCACACIGCTATTGATCTTAA.PCGTCACTTTTCQT GCA CCAGCGTTTGCQGACSACGC4-'AC?2CTGATAC-TGTGACCTTGCACAGATTTAPTGCCACAAG CTGCA TTTG ATAACTTIACWGA.AGGTACAAAAGk,-GTAkAGAAITGATAGCSATTATGTTGGTAAACAAATTA %ATG ACCTT 50 AkATQTT.ATTTTGGCTCACCGATGCT42S AGAAATC-AAGGGTGCTTTCTTTGTT TCAAA ATGA.ACTGGT ACAAAAkTTCATTACTGkAA;TGGTAAGGAAGTCGATACTTTGGAAGCTAAAGATC-CTGAAG GTGGTGCTGTT CTTTCAGGGTTAAACA3\z AAGACAA TGGTTTTGTT TTTDAACTGCT AAGTTAAAA;%GG-AATTTACCnAATCGTT GAA TTG AAGAAAAzATCAAACTA CGATAACAACGGTTCTATCTTS GCTGATTCAJT-AAGCAGTTC ACT AA ATGACTCTGCCATTGGThCAA,-kCOAkrGTflTT(TTAAGTGCTCACATTTTCCAA iGAjTACTGA AACA.z 55 AAACCAPCAAGTAGATAArGAAQTTTG(.AG ATAAAGzATCTTGATTATAC-TGACIIACCGA--AfACACAAA.GGTGTT GTCTCAkGCGAICAGTTGGTGrACA',)AAG AATACA!TAGT' TGGAAkCAAAAkATTC TTAAAGGC TCAGACT ATAAG PAACTGGTT-TGGACTGATAGCATGACTAAA tiGGTTTGSACGTTCAACAACM& AGTTAAAGP CTAAiCATTGQATGGT GAA-zGATTTTCCT43T TTAAA CTACAAA CTCGTAACAGATGACCAAGGTTTCCG CTTGC-CTTGAAk'TCnAtCA GSTCTT0CAGCAG-TAGvCAGCAG CCTGC3QAA3GAiCA12GATGTTGzAAA"TC~zAATCACTTACTCAGC-TACGGTG 60 AAC-GGCTCCAC-TACTGT TGAAAt7TTCCASAAAkCCAAWTGATGTTAAAT TGCAC-TATtGTAATAACCCAACGGAA- -103 5GAAAWSAATC.-7.CACAAG-AAGG TACTCCA, GCTA' ACCAAGAAAT TAAAGT CAT"AAAGAC TGGGCAGTAG.ATGQT ACAA7%TTAC.'-TGATGCTATGTTGGAGTTAGk, CTAXTCTITTACCTTGCAAG ;PAAAC AAACG GATGGTACAT,-GG IGTGAAC GTTGCTTCACACGAAGCAACP'AAACCATCACGC-TTTGA.2ACATnCT-TTCACAWSG TTTGGA,-TMT 'GCT 1 SAAACTTACCGCGTTGTCGIA%CGTGTTArJCGGCTAPCACTICCAGA;ATACGTATCA'TTT1iAAA: ATG GTGTTGTG 5 ACTATCAA-GAAQAPACAAAA ACTCAATGATCCACT-C(2ATCACCCACAGAAtiCCAMA %. GTGGTGOACTTA%.T GGACGTATTTGTAM\jACA%'JTCAGCTAACATGAACGCTTGGCAGGACTACCTTCTGTTAGAA'-2 GAA GGCAA;%ATACTTGGCACGTiAAGAGGTGCTAuG.AAC TGC TGA AGCAAA GGCAGCTQTAAMU.ACTGCTAA CTAGCCATTGGATGAAG~rCTGTTZ,A4AGC-TTATAACGACTTGA-TAAG kAAAACAAG.CAAGGCCA sAGAAG GTAAA ACAGCATTGGCTACTCTTGATCMAAA4.uCAAAAzGCTWA,'CAATQ.ACGCTTTTGTTAAAGCTAACTAC-TCATAT 10 GAATGGGTTGCAGATAAA.ZAGGCTGATAA.4TCTTG TAAkATTG3ATCTCTAACGCCGGTGGCTCAATTTGAAATT ACTG'TTTGGA'rAAA. GGC''AC^TTKTGG CT TGGA-AGAAACTCAAGCACCkSCAGGTTATGCGACATTGTCAGGT GATGTAA ACTTTGAAG TA.ACTGCCACATCT(,TATACA.AGGGGCTACAACTGACATCG-CATATGAT AAGC TCTGTA. A-AAGAzTGCC-CAACAAGTTCAAA ACAAAAA7AGTAACCATCCACAAYACAJGTGGTATTGGTACA 147TCTTTTCA.CAATTATTGGTTTAGCATTATGCTTGAGCAGTAGTTATCATGAAAAACGT-AATCAGAG 15 GAAc-CTTAA GET amino acid seune(EQ3 Q 26) KSYFGSTDAEE I GAFFVFKNETGTKFI TENGKEVDTLEAKD AEGGAV LSGLT tDNGFV FNTAELKG1 YQ IV ELKEI<SNYDNNGS ILADSKAVFVKI TILVN NQGVWVKDn-HI YP: ITETKPQVDKNFADKDLDYTDNREDKGV 20 VSATVGDKKEYIVG '(TKILKG/ SDYKKLV7WTDSMTKGLTFINNVKVTLDGEDFPVLNYKLVTDDQGFRLALNAT GLAAVAAAAKDKDVE I I TYSATVN-GST-TVE IPETN'eDVEILDYGU4NPT-EESE PQEGTPANJQE I VI KDWAVDG TI TDAN-VAVK'-Al FTLQEI QTDGTWVPNVASHEATKPSRFEHTFTGLD JAKTYRv 7WRVSGYTPEYVSFKNGWA TI KNNKNSNDPTP INPE DEVVTYGRK-YV KTNQAI.4TE-RLZ A,-TFVFKKGKYLA RKAGAATAEA7FAAVTF-AK LALD EAVKAYNDL!TKEEQEG,-QEGKTALATVQ KQKAYNDAFVRZUIYSYEWV ,ADREADW iKv.LI S -AGGQFEI 25 T GL, DI GYGLEFETQAPAG-YATLSG,,-DVNFEVTATSYSKGATTDIAYDKGSVKDQ, QVQN XVT IPQTGGI GT ILFTI IGLSIMLGAWIMF~tKKRQCSEEA _________ Strain 1C458 GET DNA seq ue-nce (SEQ ID NO: 169) i0 ATGAAALAAATGAACAAATATTTTGC-AGTCTTCTGGOGTTGQTA'CTGACCGTAA2-CATCAT TGCITCTAGTT GCACCAGCGTTTGCGGACG AAGGAACAACTAA-1TAO.AGIGACTTTGCACA.AG(ATCTTGCAACTGAATCAAT' CITTAATAAAAGTAAC,-TTGCCCAGG(ACTACAG GCCTT;AAlGGPJ2, ATGA CTATAA;AGGT GAATGTATTTGTGA CTTGCTGAATACT TTGGATCAGGTTCTAJA&,iiAATTGACGGTGCTTTGTTTGGTTTGGCTTTAGAAGlcAGGAA AAAGCATGGTGT' CGTACAATATGTTAAGGCAAAA GCAAA TGACAA7ATTAAOACGAGAG-TT-AATTACT~zAAGGT 45 A-CACGTGCAG ACAAMAAGTTG~ISAGAiGCTGTA GTGGTTTGACZC TGGTACGGGTATTGTTTTCAAT A'CAGCTGG'TT-G;AAGGTAATTTGAA?.ATTAzTTGAA-zTTGAAADACAAAkTCAAGTTACAA-kCnATAATGGTTCG CTGTTACCAGGTTCAA AAGCAGTTCCGGTGAAAAATCACTCTT JTATTGGTAAGCAAAGATGGTGTTGT TAAA GATGCACAC-GTTT-ATGCAAkAG3AOACTGAAAG AAACCAGAAGTAGA CXjC-L .CTTCGCTAAPAACAAACGAT 7TGA4 CAGCTCTCA4AAGACGCTACTCTTCTT~zAGGCTAGGTGGAGlACTACAkAIATAzTTGA GCGACTAAAGICTC 40 AGTGTAACAGOTGAAATCGGTAAAQTTA.TCCCTTACGAAGTTAAACAAAA GTTC'TTA?.AAGGTTCTAAAA GA7%2,AAATGGTTTGGACCGA3TACCATGTCAA %ATGGTTTGACAATGGGTGA-TGkATGTT AACCTTGCAGTTTCA GGGACTACAW2.AACTTTCATTAAAGATATAGA'TT4AOACTCTTAGCATTGATGACCGTGGTTTGACATTGAAAl ' TITCAAkGCTAGTGG AT TGGAGAAATT GGAAGAAG-AGCAAAGCATCTC4AT G TGAAT TTACATT GAC TTAT A? 1AGOTACTGTTAAz TGGOCAAGCAATTATTGACAACCGAGAAkGTCAATGA,'CATCA'AATTGGACTATGGTAAT 45 AAAGCT GGTAGAGAT T TATC AGAACAAC C TOTGAC AC CTGA.AGATG GTGAAG TTAA AGTGCAC T AAA.A-AT GG GCAG CAGGTGCTA.ATAAAGCAGACGCTAAAGTTCTCTAGAGC-ACTTIAAAAA -2TGGTACTAAACAAGTCGTAGCT TCTGTCGGATTGA CCGCAGCTGATACAAA'AGGTAG-GATTAATO.TTGGTAAAGGGATGACCTTTGAAA-TCAGA' GGAGCTTTC-TCAGGTAGCATTCAtAAGGCCTTCAAAATAAAGGCTTACAGCTGTTTCTGAACCTGTTGCAGGTTAT ACTAATGCTATTAATGT TACTGGTAATGCTGTTGCTATCAGCAATAG-ACCAGACAGTGACAATCCAACGG'lCA 50 CTTAA %C CAAGTG~A~CCAAGTTr4A ACAGATGGTAAVGAP ,ATTTGTCA-ZAGTTGGCGATGCAGATGCG'GC TTAGCTGGTGCACAATTCGTTGTGAAAAzATTGAGGCTGGTAATTCCTTGTCTTAXAGA-AGA m GCAGGTGT"A TCAGGAGCTCAAAG TGtiAATTGGC? ACTGSTAAACAGACTTGGATAATGCCA CAYAAGGTTACAACGGTTTG A CAAA4G C GCAGC-AAGAAGGT GCT GA TGGTACA TCAGCAAAAGAAC TT AT CAAC ACTAAACAGTMcAGT TAC GA.CGCAGCCTTGATGAAAG PCACGTACAGCTTA:TACATGGGTAGATGAAAAAG'Vl-TAAAUGCTATTA CCTTCACT 55 TG1AA.TkATCAAQ(GTCAATTTG AA GTTACTGGTCT7GAGTAGG TTCTTAGAAAGTTGAAGz'AAAPCTCTTGCA GGAGCAS2GTTATGCTAA;ATTGTCAGGCIGACATTGAGTTTACAGTTGGACACGATTCTTACACAPGTGGTGAC AT CAAGTACAAGACA GATGAT GC TAGCIAACAT GCAC.AA A-AG TTT TCAeA.AATAAG TAAC CATOCC ACPA t ACAGGTGGTATTGGTACA'ATTCT TTTQCAI,',ATTGG TTTAAGCATTA ,GC7TTGGAGGG( GTAGTTATCATGy AAAkAGAG GT cAAT CAGAGGAAGC T T414 60 ORE ami~no acid seq:uence (SEQ ID NO:0 127).

-104 M-KKINXYFAVFSALLLTVTSLLSVA7;%PAFAzDEnTTN-TVTLH d LQTESWLNKSNFPGTTGLNGDDYKGE SI SD tAEYFGSGSKE 1 DGAFFALALEEEKDGVVQYVKAEAND: .LTFDLI TKGTF TTTK'VEEAVGGLTTGTG IVFN TAGLI<GNFKI IELKDKSTYNNNGSLL~aASKAV.%PVK I TLPL:VSKSV%VKDAHVYPKNTETKPEVD MFA' KTND IJTALI DATLLKAGADYKNYSATKATVTAE'IGEVI PYEVKTKV LKGSKYEKU &~fTDTM,,SNGLTMG"DDVNLAVS 5 GTTTT SI KDI DYTLS I DPRGFTLKF tATGLDKIEEAAKASDVEFTLTYKA&TVN1,GQAI I DWPEIVNIDI KLDYGN KPGTDLSEQ-PVTFEDGEVKVTKTWAANtIKADAKVVYTLKNAkTKQWAISVALTAAiDTKGTI NLG. GMTFEI T GAFSQTFhC LQNKAYTVSERV AGTTNAINtVTGNAV"qAI TNTPDSDNPTPLN;PTQKETHGKKFVKV",GDA)A.R LAGVAQWVVKNSAGKFLALKEDAAVSGAQTELATAKrI{TDDNAl RAYNGT, PA-jQQEG,-ADGTSAFEL 1 ?TSQSA4 Y DYAAF1 KAPRTAYTWVDEKTKITFTSNNQGQFEVT GLEVGSYKLSETLAEPAGYAnI(SGD1 EFTVG2' :DS'YTSGr) I0 IXYKTDDASNNAQVFNR- KTIPQTGGIGTILFTI lOLSIMLGAXINKRRQSEEA Strain 1C459 ATGAA,AAAATCA, ACAAA-TGTCTTA CAATGTTC-TC A CACTGCTATTGATCTTAACGSTCAC-TATTCT-AGTT 15 GCACCAGCGTT TGCGGACGACGCAAPCAACT GATACT-GTGAC,'CT TGCACAAGAT TGTCA7,TGCCACAAGCTGICA AAr ATCTTATTTTGGCTCAAkCCGATGCTAAA,-GAAATCAAGGGTGCTTTCTTTGTTTTCAAAUATGAT$ACTGGT ACAAAATTCAT TAC TGAzuzAT GGTAAGGAAGTCGATACT TTGGA.GT'.AXAGATGCTGAAG,.'GTGGTGCTGTT C-TTTCI CSGTTAACAAAAGACATGGTTTTGTTTTTAPACACTGCTAkAGTTAAAAzGGAAiYTTACC~kATCGTT 20 GAAT TGAAANzCCAAACTAGATACAACGG-TCTATCT TGGI-CTATT--A7- AG',AGTTCCAGTTA.A ATCACTCTGCCATTGGT-AAACACCAAGGT GTTTAiztUATGCTCCATTTATCCAAAAZTACTGAACA zAAACCCAA0 TA-GAT.AAGP A-CTTTGCA-ATAAA CPATCTTGAT-TATAC-TGACA('CGAAA.1GAC,-A-3 GT G TCTCA.SCGACAGTTGGTGACAAAAGAANTA'CATA'iGTTGGj!AO? 4jJTATTCTT'AAGCTCAGCTATAAG AACTGGTTTGGA, CTGATAGC ATGACTAA4AGGTTTGACGTTCAttCAACAAZCGTTAAA.GTAACATTGGATGGT 25 (AGA~jTTTTCCTGTTTTX-A.%ACTACAPAACTCGTAACAG ATGASCCAAGGTTTCCGTCTTGC-CTTGAATGGAACA GGTCTTG CAGCAGTAGC.AGCAGCTGCAPAAGACAAAG,'dC-TTGAIAATCAACAPTCACTTAC-TCAGCTAC-GGTG AACGGCTCCACTACTGTTGAATTCCAGAAA CCAATGATGTT-)AATTGGACTATGGTAATAA-CCCAACGGAA 2 G7AAGTGAkACC-ACAAG AAGGTACTCCAGCTA 2 ,CCAAGAAP ATTAAAGTCATTAAAG',CACTGG 'GGTKS3ATG GT ACA'ATTACTGATG 'CTAATGT GDAGTTAAAGC-TATCTTTACC'TTGCAAGAAAAAkCAA AC(SGATGG TA'CATGG 30 GTGAACSTTGCTTCACACGA.AGCAA-CAAAA-VCCATCAC-GCTTTGA.ACATACTTTCACAGG.TTTGGA-TAATGCT AAAA 4CTTA CCGCGTTGTCGAACGTGTTAGCGC.CTACACTCC-AGPJATACGTATCATTTAAAAATzrGGTG TTGTG ACTATCAAGACAAA- '~AAAACTCAAA TGATC A-ACTCCAPATCA.ACCCATllCAGAACCAAAAG,'TGGTGAC'T lTT GGACGTAAATTTGTGAAGTCAA7AGCTACACTGAkCGCTTGGCAGAGTCCTTCITCGTTAAGAAA11 GAAGGCAAATACT TGGCACGT,'AGCAGGTGCAG:CAACTGCTGAA.GCAAAGGCAGCTGTAAAA-1ACTGC2TM-A 35 GTAGCATT(GGATQAkAGCTGTTAA-IGCTTATAACGACTTGACTAAAGA.AAA CA-AGAA.GGCCAAGAAGGTAzl ACAGCATTcGiCTACTGTTGA TCAAAAAL& CArAAA'kC'C~z ATGACGCT'-TTTGTTA-AAGQTAACTACTCATAT G-AATGGGTTGCAGATAAAA GGCTGATAATGTTGTT~aAATTGATCTCTAACCCGGT1GTCAATTTGAX ,TT ACTGGTTTGGAT;Az AGCCACTTATGCTTGGAGJ ACTCALAGCACCAGCAGl~GTTATGCGAC-ATTGTCAGGT GA ,TGTALA-ACTTTGAA-GTAACTGCCACATCATATAGC-AAZGGrz2GCTA(nA3%CT3ACATCGCATATGATAAAGGC 40 TC T GTAA.AAAAJAGATGC CCAA CAA GT TQCAAACAAAAAAG TAAC-CAT CCCAC AAAkCAGG T GGTAT TGGTACA ATTCTTTTGAkCAATTATTGGTTTAAGCATTATGCT TGG7AGCAGTAGTTATCATGA-z AAAACGT CAATCAGAG GAAGCTTAA QRF aiatno acid se~uence (SS Q ID NO:," a28): MYKKIN KCLTMFSTLLLI LT SLFSV APAFADDATTDTVT4{KV3FQAVAFDINFTEGT KGKN4DSDYVG( KQIDL 45 $3YFGSTDAKE I KAFFVFI NETGTKFI TENOKEVDTI 2 EAYKDAEGGAVLSGLTRDN)tGFVFN'TA'KLKGl YQI, V ELKEXSNYDNNGS ILADSKAV'PVK.1TLPFLVNNQGVVFKDAH IYPKUTETKPQVJDNNFA DKDLDYTD)NRV.DKGV VSATVGDSREY IVGTK 1 LKGSDYKKLVIWTDSMTKG ITFNNvNVKV.TLD'GEDFPVLt. j-KLVTDDQGFRLALNAIT GI.AXAV AAAKDKDEIKITYSAT-VNGSTTVEI PETNDVKLr)iGNt.1PTEESEPQEGTPAiQEIVKDsAVDO( TI TDAt AVKAI FTLQEKQT DGThNN' ASBEATXSFFEHTFTGLD~fNA TYRVVE'PRVS5GYTPEYVS>FKNG V 50 TI KNNKNSNDPT F INPSEP VVTYG RKrIKTNQANTER AGATLKKEGKYLARK.AGAA.TAEAXAAV, KTAK LALDEAV!KATYNDLTKWFQFEGKTAAVDQ QKA.YNDA FKAN YS3YSWVADKKA-DN KL ISNAGOQFE I TGLDKGTYGL-EETQAPAGYATLSGDVNIkFSVTAT SYSK ATT!)lAYD OSV{KDAQQVQNKK'VTI PQTGGI OT I L F TI-. IGLS1 MLGAVVlI MIKRQ S EEA 55 rStrain 1C460 ORF DNA sequence (1250 If) N40 1711 IATG AAAA, GAATCAACAAATATTTTGCAATGTTCTCGGCATTGTTACTGAOTTTAAICGTCATTGCTCTOAG TT IGC~kccAGcGTTTGCGGATGA. GCA AOAACTAATAcA',GTGSACTTT'lGCAc'AATTTrTGcA-,Vj\O,-cGAITAAA -T CTTAACAAAAI-GTAACTTCCCAGGAA 4CTACAGGT("

T

TAAkl'GGAAAA' GACTA'-CAAAGGC-GAG.CTATTTC-TGAO 60 CTTGCTGGTTACTTTQGCGAGGATCTAAAkG2AATCGA2AGGTGOGTTCTTTGCTTTAGCTTTGA-AAGAAGAT -105 '%., GTGGTA XAGTGCAATATGTT ,ACGC. AAA2GAACGTAA 'AAATTAACACCAPGCCTTAARTTAATAMC-AAT CC TACTCCTCMAUlT.AA-CAGTYAAAATiuT CA'GAGGCCGTCTGGATTGAC'CCAG-AGGA.lGATACTGQ- ?2,,T T 1GTTT TCAIXCACCAAA-'-GCATTGAAA6GGCGAGzTTTAAAATTGTTGAAGCTTAATCAA-AATCTACTTACnA,,CAAT Ui kT( GTTCCCTCCTGQCTCTTCJWAGCGGTTCCAG TTAA2CATCAQTCTTCCATTGG3TAATGAAGATGGT GTTCTTCCTCATGCC ATCTTT ATCC-AAAGAACACTGAP.AAAAACCAG AAATTCATAAAAACTTTCCTAAA &tTGMAkAAG-CA.ACTGCTACTG CTQ-AAA TCCYGTAAAC-GTTGTTCCTTATGAAGTTA, AAAAAAATTCAzCAAk CCTTCTAAATACCAAA.-CTTGGzT-TGGACACATATAAITCTC.AA ATGTTTCAATGGGTTCAA;CTCTTACC CTT? kAACTTCAGG AACr-TAC-AGAAACT-"TTCCTAAGATAC-AGAPCTATG-AACTTAGCATTGA CCCTG GT 1 T TC2-CATTAAAAT TCACAGQTGATGG-ATTGGGCAAzT-TGGAAAAuAGC-AGC TAAAaACAGC TGAT ATTGWT T ?CA4TG'ACTTATATC-TCTAC-TCTTA-ATGGTCAACCAATTATTGATAT CAAATCCAATG ATA CAA;ATTG (-'GTATGG.TAAC.AAACCAGGTPAAAC.TGACT PACTTCcTGTnck'ACCIT~CAAGTAAVGTAACPGTT GC TAAAACT TGTCTGCCGvAAT TGCACC TATGGTGTAAACGTTGTT TACAC AT TGP4AGATAA;ATAAA AC~ TGCTTCGTTCTTACAAAAACTCTAAAGCTACAATCGAC-CTT-GGAAATGGTATCA4AATTTG AA 15 CT? CTCGTAA4CTTCTCGGG'TAAATTCACTCLGTCT.AGAAA.,ACAJATCA'TACA3TS3ATC.TCASAAl CCGTTTCT &S-T AC-GCAACTGCAA TAAA TCTAGAAATGTAA.ACTAAC-CATTA CCAATACCA.AC-ATTCTGzATAACC-CA. P. -ACCATTGAACCCAA'.CTCA' ACCAAAA'GTTC.,.A(. CCTGG-T,'AQAATTTGT-ArAA CTAA, TGAACAACGT GACCGTTTGG.CTCGTGCACAATTCGTTGTG.AA,,AACTCACAGGTAA.ATAC(CTTGCT-CTTAAAGCAG -, TCAA 'C 'C kACGTCAjeVAC TTTAG CTGC.TAAGL-AATAGCCTTTAGAPTGAAC 4CTATCGC-TGCTTAThAGAAG ITGz 20 TCTC CAA7 CAGACCA.2AAA.d3GTGA.AA~AAGG.TTACT-GCtAMAGA.,7.AC.TTATCAAA.ACTA; AACAAGCAC%.ATTAC CGAT(;CAGC-CTTCATTCAGCC-TCGTAC-AGCT TATGAGTGGz-AT AACACATAACSCTASACCCATTACCTAkCACT -CAA. CGATACGTCAATTTGAAGTTACGTCTTGCAGCCGT2 TTACACTCGAAALCCTTGCT cCAGcACGATTTCTAC3TTGCCAGGTAAT4'-ATTAAGTTT GTAG TTAATCA.k~GCGG CAXrACATAiACAC-GGT AACATTGACrTACCTTCCTAACAGCAACCAAAA, GATCACAGTGTAAA.,ATAAAAGTAPCAATCCCA 25 1CAIA.CAGGTCGTAzTTQ GThAAPTTCTTTTCACAAT'A'TTGGL'TTTAAG CA'TT-ATIGC'TTGGAGC JTACTTAT~C IATGt'-AAAGACCCCAATCA-AAGCQAAGCTPA iORF amino acid sequ wice (SEQ I D NO, 12 9) LAIGYFGOESE IEG-AFFALALREDKSGVQYVKeAKEGNKLTFALTNKr a 'PET TVUI DEAV'SGLT PEGDTGL .30 VFUiTEGLKGEFKIE lVKSKSTYCiNNG,,SLLAASKAVPVTI TLPLVINECXNV"%fADA!4VYPKN4TEEKPE I CNFA.K ITNDLTALTDVNl-RLLTAGANeYGNYARDK ATATAET GK'VVPYEVKTK 1HK<GSRYENLVWTDIMSNGLTKG STVS LKASGTTETFAKDTDYELS IDARGFTLKFTADGLGELEKA.AKTADI EFTLTYSATVNCQAI11 NPESNDI EL SYGNI PGK DLTEL PVT PS8KGEVTVAKTWSDG IAFDGVN',VV2TLKDKDKTVJASVSLTKTs FGTI DLGNG IKEE VSGNFSSKFTGLENKSYCI S;'ERVS.c'GYGSAINLENSIGVT ITNTKDSDN PT PLC PTEPKVEFTHGKEKF'7<TNEQG. 3.5 DL' :AGA,,QBVVE'%rNSAG YLAL.KADQSEGQKTXLAAEI{ IALDEAI1YN WLSATDQKG-EKGI TAFELI IT QADY DAAFIEARTAYEW ITDKAP.AITYSDGFV-GArTNETLPG K-INKrJV'n h7GcSY I -TG NIDYVANSNQKDATPRENKKVTIPQTGIGTILFrTJIGLSIMLAVVI71TMKRQSKEA Strain 1C461 40 OFF D14A sequence (SEQ ID NO: 172) AkTGAAAAAAATCAACAAATGTCTT ACAATGTTC TCGACAC TGCTAT TGAT CT TAA CGTCAOT",ATT CTCAG-1,TT GCACCAOCO-TTTGCGGA3CGACGCAACAACTGATACTGTGAGCTTGCACAAGATTGTCATGCCACAAGCTGCA TTTGATA.ACTTTAOCTGAAGGTACAiAAGTlAG2^,'IXGAT.AG2CGATTATGTTGGTAAIACA?.ATTAATGACCT AA ATCTTATTTTGGCTCAA .CGATGC TAAAGAATCPAAOGTGCTTTCTTTGTTTTCAA.AAtvTGApAACTGGT 45 ACAAAATTCAtTTACTCAAAATGGTAAGGAAG TCGATACTTTOGAAOOGTA AAGATGCT GAAGGTGGTGCTIGTT CTTTcAGGGTTAACA.M AAA,%AnGTTTT;TTTTTAACACTCTAAGTTAT hAGMTTTACCAl ATCGTT GAATTG AAA G7 AAAATC;'AAOTACGATAAPCAACG TCTATCTTGCCTGrATTCAAAA.GCAGTTCCAGT TAAA ATCAOz.TCTGCCATTGGTAAAPCCAAGGTGTTGT'TAAGPATGOTC.ACATTTATCCAAAGAATAC,-TG AAA'CA AArACCACAAOTAGATAAGAACTTTGCAGzATzAACATC 2 TGAT- TATAGTG 1 ACACCGAAAA(kC;CAAAO GTGTT 50o GTCTCAGOC.-AGTTGGTGAC %AAAAGAATACATAGTTGGPACAAAATTCTTAAAGGOTOAGACTATAA%-G AAPACTGGTTTGGACTGATAGCATGACTAAAGGTTTGACGTTCAAICAACA-ACCTTAAAIGTAAC7-CTTGGA TGGT GAAGATTTTCCTGTTTTAAA CTAOAzAACTOGTAACAOA'TOACOAAGGTTTCCGT. CTTGCCTTAATGCAACA GGTCTTGCACCAGTnGCAGCAGCTGCAAFAAGACAAA Gn'TGTTGAATCAAC'ATCACTTACTCAGCTACGGTG AACGGCT CCACTACTOTTGAAATTCCAGAA.AC(CAATGA'iTGTTAAATTGGACTATGGTAATAACCCAACGC-A 55 C?,-GTACCACAAAGTATCCGCTCCAGA AT AAAGTC TTAAG(-ACTGGCAGTAC- GATG AATTACTGiATGOTAATGT 'TGACCAGTT,AACCTATCTTTACTGC GAAAACAPAOGGiCATGGTACATGC OTGAAPCGTTGCT-C^CACGAAGCAACAAzAACCATCACGCITTOAAOATACTTTCACA.GGTTTGGATAA TGCT AAM.1CTTAOCGCGTTGTCGAACGTGTTAGCGGCTACACTCCAGAATTACGTATGCATTTAAnA-ATGGTGTTGTG5 ACTATCAAGAzACAAC-AAAS.CTCAAkATOATCCAA /tCCAAlTCAACCCATC-AGAACC AA-AGTGGTGAkCTTAT i 60 GGACC;TAATTTGTGAAPUJACJkATCAAG ,.TAAC C TGAACCC'TTGG CAGGAGCTA7 CCTTCCTCG-TT;AAAA -106 G AAGGCAAA -TACTTGGCACOTAAAGCA GGTGCAGCAPACTGCTGVAAGC,AAGGCAG 'CTGTAA jAAACTGCTA.A CTAGCATTGGATGAAGCTGTTAAAGCTTATA- CGAC'TGCTAA'GAAVAAC-XGIAGGCAA -AAG(GTAAV ACAC-CATTGGCTACTCTTGATCAAAACA AAA 2AGC-TTACAATGACGCTTTWGTITAAAGCTACTAOTCATAT GAAT GGG TT G CAG ATLAAAGC T GA TAAT G T TGT TAAiT TGATC T CTAACGCGGrG GT C AA T TT GAAT T 5 AOCTGGTTTGGA TA.AAGGCAOTT-ATGGCTTGGAA GAlAOTCA AGOACCAGCAOiGTTATGCGACATTGTOAGGT GA -1A G -TAz CCACTCTATAIAAGGGGCA ACTGCTC TA AG TCTGTAr AkAAGAATGCCCAACAAkGTTCMP-AA.'CAAAAi-AAGTAACCATCCCACAA %.CAOGTGGTATTGGTAICA i 1 AlTTTTTTCACAATTATT GOTTTAAGOATT ATGCTTGGAGCAGTAGT'ATCA GAAA, AACGW-AATCAGAG I GAGCTTAA 10 ORE amino acda 7ae, DN: 3f MM.0 - NKCLITMFS.CTLI L1TSLF'SVAPAFA'DDATTDTVTLH IVN PQAAFDNIFTEGTKG KNDSDYvQCKQ INOL It OFSTDAKEITKGAFF-VFKN'ETG,-TK<FTTENG(KEVD)TLEFAKDAEGGAVLSO- (LTR)NGEVFNTAKL JG1 'QIV ELKEKSNYDUNGS~I LADSKA%?VVKITLE'VNNQGVVKO71-AHI -YPKN-TETK/PQV-' DRNFADKDLDYTDNRKDRGV V#AIDKKEY IVGTKlIIKGSOYKL7'dTDSM4TKGLTFNNNVt',KVTLDO-EDFPVLNfl(LVTDDQG-FRLALNA.T 15 GLAAVAAKD1Dr1cKTY 0 ATVNlGSTT~VE I PETNDV'%KLDYGNNPT EESEPQEGTPANQEKV5IKW 'AVDG I ITDANVAV'iKA I FTLQEKQTDGTIPJ VASHEATEPSRFEHTFTGLDNAKTYRW' ERVJSGYT PEYVSFKNGVVJ I IKNNKN 4 NDPT 22NPSEPK'VVTYGREEVKTNQAN4TERL, 4 A GATFLVKKEGKYLARKAQAAP-TAEA A'VJKTAK LADDEAVKAYNiDLTKEKQEGQEGKTALATVDQKQKAYNDAFVKANYSYEWgVADKKADNMVKLISNAGGOFEI . LDGTYG1EETQAP;AGYATLSGDVNFEVTAs SYKGe(ATfI 'YDC WKRDntQQVaNKFKVII ?QIGGI-G.

20 ILFTI IGLSlNLGA7%TVMKKRQSEEA Strain iC462 CR2 NA ecjunce(SEQ TO NO; 1,3); ATGAAATCAACAAL ATATTTTGQ. 4ATGTTCTCGGCATTGTTAC TG-ACTTTAACGTCATTGC'-TCTCAGIT 25 GG-ACCr.GCGTTTGO-GOATGAkAGCAkACPAC'TAATAOAG TOACTTTGCkAAAGA.TTTTGCPkAACCG tATGAAkAT C7TTAACAPAAGT.ACTTCCAGGAACTACGTCTAC.GGAAAGACTACAA. GGTGGAGGTATTTCTGAGk CTTGCTGGTTACTTTGGCGA GGGATCTAAAuGAAATCGrAAG-GTGCGTTCTTTG CTTTAGCTTTGAA AGAAGAT A,,AAGTGGTAAAGTGCAATATGTTA AGGCGAAAAGAA %GGTAACAA.AT1'AACACCAGGCTTAATTAATAkAGA T GGTAGTCGTGAAATlA AATAATATTGATGAAGGCOGTGTOTGGATTG ACAO'-CAGAG-GGAGrATAOXTGGAtCT 30 GTTTTCAACACAAAGGr-ATTCAAArGGGAGTTTATGTAGTATATTGTCAAT AAZTGGTTCCCTOCTGGCT GCTTCAAAAGC GGTT4CCAGTTAAC f ATCACTCTTCATT&STAAATGAAGATGGT GTTGTTGCTGMXGCCOATGTTTAT-CAGAAOAG J iGC-AAGjAAACAGAiAATTGA-TAA? OITTWGCTAA P~AAAAGATTTGACAGCATTOACAGATGTTAATAGAGTTTTGACAGCTGGCOOAAAt)%TTA.TGGTAATTATGCA CGTGAICAAAIGCA4ACTGGTACTGG-TGAAATCG GTAAAGTTGTTCCTTATGAAPGTTAAAACAAAAATTGACAA 3j GGTTOT AAAAGAAAAGTTGGTTTGOACAGATATAiATGTCAAATGGTTTGACAATGGGTTCAAGITGTTAGC CTTAAA-PGCTTZCAGGAAUCTAC .,GAAACTTTTGCTAPAGGATACAGACTATGAACTTAGGATTGA.TGCGCGTGGT :TCA CATTAAATGAGAGOCYTGAPiTGGATTGGGCAM~TTG,4AZXAAGC GGTAAAQAGCTGAPTATTGAATTT NCATTGACTA AGTGTACTTTAATGT AAGCA.ATTATTG.TAATCAGAATCCAA73TGATATCA-AATTG VCGTATGGTAACAAAzCCAGGTA2AG~rACTTGAG-TGAACTTCCTGTTACACCTTCAAA' GGGTGAAGTAAGAGTT 40 GG-TAA CTTGOTC"TOACGC'AATTGCAGC"-TGATOC4GTAACGTTGTTTACATTGAAGATA %AGATAA AC^TGTT GCTTGAGTATCATTGAGAAAAAC-ATGTA)%AAGGTACA'ATCGACCTTGGAAATGGTATCA ATTTGIV GTATCTGGTALACTTCTCGGGTAA ATTCAO TGGTCTAGAAAz ACAAATCATA CATGATGTCAGAOGTGTITTCT GGTTACGGAAGT GCAAT.TCTATGAM- ATGGTAAGT.('A CCATTGGAAVTACC"A3AGA ITTCTG'ATXAAGCCA ACACCATTG A ACCTAC'TGAACOAAAAGTTGAA 'ACTCATGGTAAr GAA ATTTGTCAAA-ACTAkATGMkACAAGGT 45 GACCG'-TTGGGTGGTGCAGA ATTCGTTGTGA-P'CTCAGCAG GTA-,'AAACTTGCTO-TTAAGP,,CAGA-iTCAA TOAGAAGGTCAAAPCTTAGCTGCTAAGAtAAT-AGTTTGATGGTA'T'CGCTG2TTATAGMGTTG TC-TGOAACAGACCAA~i GGTAJ4AA^,IGAATTCTGCAAAGAOTTATCAAACTAACAAGCACGATTAC GATGCAGCCTITCATTGAGGCTCGTACAGGTTATGAGTGGATAACAGATAAVGGCTAGAGGCCATTAGCTAGCACT TOC;AAAOGATCAA;5GGTCA ATTTGAAGTTAOAGGTCT'TGCAGACGGTACTTACAAOOCTTGAAGM-PACACTTGGT 50 CCAGCAGGATTTGCTAAGTTGGGAGGTAATATTAAG(TTTGTA IGTTAAITCAk, 3G00TG:ATAGATAAiCAGGTGGT AA CATTY GACT ACGTTGCT AACAGCAACGA.AAGfATGCGAAGT-TAGAAAATAAAAAGGTAA.CAATCOCA CAAlACAGGTGGTATTGG'-TOJ rATTCTTTTCC.CALATTATTGGTTTA AGCAT TATGCTTGSGAGCAGTAGYTATC 2CATAAAGACOCGAATCAkAAGG AAGOTTAAk ORE amno 2une(E DN:11 55 MKRPTNKYFAM1FSALLLTLTSLLSV APASFADEA'TTNTVTLHJEILQTESNLNKSNF PGTTGLNGKDYKGGS-ISD LAGYFGEG SKE IEGAFFALALKEDKS>GKVQYvKAR$.EGN-KLTFPAL I NOG T PEI IMVNI DEAVSOGLTPEGDT GL T-NDLTALTDVI!R14.TAGAkNYGNYARDK<ATXTAE IGE.VV PYEVETKI HKGSEYENL',VWTDI NSNGLTE GSTVS I LKASGTTETFAKDTD)YELS IDARGFTLI FTAEYLREAKAISIl STWQIIOPSOE I0 SYGN4KPGKDLTSLPVT-PSRGEV'TVIATWSDG-IA'PDGVN JVVYILKD'KDKTV ASVSLTKTSRGTID OLNG IRKS 107-~ DRLAAQFVKNAGKIAL{ADSETLTAA KKIALDEAInAYNKLSAT DQKGEKGI TAKE L I KTKQADY IDAAFXEARTAYEWI TDI(AIAITYT-SNDQGQFrEVTGLADG-TYNLEETLA2A GFA'KLA, GNI K VYPNOGIY 1TGG Strain IC470 ORE DNA sequence ISEO 1D NO: l74):

ATGAA

1 JkA.A.A.TCAACAAATTCTTACAATTTCTCSACACT GC-TATTSATCTTAAQSTCACTATTCTCAGTT GC ACCAGCSGZTTSCGGACACGCA.ACAAC-TCATACTGTGACCTTCACAGATTGTCATGCOAOAAGCTGCA .0TTTSATAACTTT ACTSAASGTACA-'AACGTAASAATC ATAGCGA.TTATSTTGTAAAAPAATTAATG ACCTT

PAAT

m CTTAT:TTCGGCTCAACCSiATGCTAAA, GAAAW-CAGSGTSCTTTGITTTGTTTTCAAAA.ATSAAkACTSST ACAAAAT T CAT TAC TSGAAAT GG TAAOSGAAG TC GAT ACT T TCSAGC TAAASAT GCTOAACGTSGGTGC TGT T CTTTCAGGGTTAACAAAAGAOAATSSGTTTTGTTTTTAACAC-TGCTAAS%,'TTAAAG-AATTTACCAAA.TCGTT SAAT T GAAGAAAAiT C AAAO TACQATAACAACS T TC TATVC T TSGC TSATTCAA.ASCASI T CCAO TTA AA 15 ATCACTGTCATTGGTAUtACA COAAGGTSTTS TTAAAGATCT'AATTTATCCAAG ATACTAAACA AAC CACAAG TAIGATIAAGAACT TT CAGA TAuVAGAT CT TIA T TATACTGAC AAQ CGAAGACAAAGT GTT GTCTCAGCSCACASTTGSTG3ACAA AAASAA TAiCATAGT TSGAAkCAKMAAT TCTTAAA5SCG'TCASACTA2 TASG AMOTSGTTTGSACTSATASCATSAGTAjASSTTTGA CSTTCAACACAACSTTAAA-GTAACAZTTGOIATCGvT CAAGATTTTCCTTTTTAACTACAAWTCGAPCAATACCAS~lGTTTCCTCTTCTTGATCAiSZCA 20" GGTCTTGCASC"AUTCGCASGTGCAAAASACRAATGTTCAtAPTCAAC ATCACTT'ACTCAGCT1CSGGG AAC&ECTCCACTACTGTTGAAATTCCAG AAACrCA-ATATSTTAtTTGGCTATGGTA'ATA7,ACCCAACSS A S7A;ATSAACCAC' ;AAAGSTA CTCCASCTAkACCPAGAMATTAAASiTCA,%TTAAYAGACTSSGCACTASA74TSCT AOAA kTACT.GATCTAATSTTG-CAGTTAA.ASCTATCTTTAC-TTCAAA~AAAACAA'ACGG;ATGGTAC-ATGG. SvTCAACGTTSGCTTCACACSCAAGCAAC-AA?4ACCATCAC-GC-TTSAACATACTTTCACAGTTTSSATAJI tCT. 25 AA.AACl^TTACCGCCTTGTCCAACCTGTTAGCGGCTAACArCTCCAAATACCTATCATTTAAAAATSSTGTTGTS ACTATCAAACAACkA l CTCAAATATCzACTCCAATC.A-CcCA'4CAGAACCA.AASTGGTGAc-TTAT GSACG TAAAT TT G TGAAAACAA-ATCAAS C TAACAC TSGAAk -CT TGSGCAOGA CTACOCT T CC TCQGTTAACAA CAAS%.GCAAATAC(TTSSCACGTAAAGCAS~rGTSCASCA.ACTCCTSAAGCAAAkGGCACTGTAAAAzACTGOTA-AAz C TASCATSGAT GAASC TGTTAAASC TTATAACCGAC TTSGAC TAAAAAAACAAAAGSCCGAMkGAGAG TA 30 . CAOCATTGSCTA,'CTGTTGATClA.ACLtAGCTTACATGACGCTTTGTTA-AAGCTAA %CTAC-TC'ATAT4 OAATGSGTTSCASATAAA-AAGSCTSATAATGTTTTAA,'TTGAT'TCTACGCCSTGGTCATTTGA&ATT AQCT T T G-,ATAAAGGC AC TTA TGS CTTGAA(GAAAC TCASCACCACAG. T'~' TATGG-A GTCA GATG3TAAkACTTTGAAGTAACTGOCAGATCATATAGCAAGGSSCTACAACTCGACATCSCA-PTATSATAASGC T CTSGAAAAAUAAGAT GCC CAA.JAGTTCAAAAkC!APAAATAACCAT CCC AC~AACAGSGT GSTAT T GGTACA -35 1ATT C TT TrCACAkTT AT TGSGTT TAAG CAT TGCT TCGGAO""AGTAG TTAT CATGAMAAAAC GT CAATCA G.z S G AACCTTAA KSYESSTDA.KE IKGAEEv,.FKNETSTKE1 TENGKEVDTLEAKDAEGSAV',LSSLTKDt4CTVIFNTAKLKSI YQIV 40 ELLEKSNY DM01 LADSKAV' PVKI TLPLVNQVVGrKDMIYPKNTET<PQVDKNFADKDLDYTDNRKEDKSV V SATVSDKKEYIVS7TKILKGSDYKKLVNITDSMT KCLTENNNVKFTLDEDPVLNY(LV.TDDQSEFRIA LNA-T GSUA,1VAAAA KDKDVeE 1RI TYSAT*VNS'STTVE I ET MDVKLDYGNN PTEESE PQESTPA-NQE I :VIKDW A7VOG TITOANVAVOAI ETLQEKQTDC-TWVN VASH1-EATKPRPEITFTGSLDNAKTYRVVERV-,SYTPEYVSFKN\PJ TTK .NNSNDPTPINPSEPKVnVTYSREKTNQAN-TERLAGATFLVKKEGKYLA RKASAA'TAEAAvKTAR TSLDKSTYSLEETQAPASYATLSIYVNEiEVTAT SYSI SATTDIAYDKSVKKDAQQVQNKKVTI POTSI ST ILETI ISLSIMLSAVVrIMKKRQSEEA 50Table II.- Amino acid and encoding DNA sequences of gbsL478 proteins derived from different strains of S. agalacdiae Strain 12401 ORFBDNA seu ence (SEQ ID NO: 204): ATSASAAA%-ATACCAPAAT TT TCTAtAAATATTSACGTTAASTCTTTTTGTTTGTCS"CAAA STACCGCTT zAT 55 ACCAATSTTTTASSSSAAT-ACCTACCSAAAATSSTCTAAASAAATTAT-TTTAl-AAASACP Ski SACCASAACAAiACCACT TTCAMASwI CTACCTT TSTT TTAAAAVCCTACTTCAC ACTCAGAAASGCAAAST7 C. .%AAASTAACTA'GASGTAACV2ASGTGAAGCTACTTTTGATAATCTCACACCGCASATTACACTTTATCAGAA. SAGACGSCACCCS;AA. .TACdAAAASACTACCAS'.CAC TTSCAASTTAASSTTAATATSAAA - lox ACGAzTAC'AA.ATAGTGATGATAiAAAATCTA TAA;TTGAACAAAGvCAAC-AtGGAACTAG7ATAAGCAGTAT CCC C T TACAGGAG CT TA TGAAGAT A C.JAGAATC TTA T AATCT TGAGCATGTTA;A !%TTCAATTCCAAA.TGGG AAA;%TTAGAGGCAAA-UAGCAGTTAATCCATATTCAAGTGAAGGTGAGCACATAA4GAGAAi ATTCAAGACGGAACA TTTCTAuzACGTATTTCA3AAPGTA-,TGATTTGGATCATATAATALtfTX 5LAITTAGTTACTGTTAGCGGT 5 AAZATCCnTALATA-AAAACTATAAATAAAG(.ATGAACC.TCTGGATGzTTGTT TTTGTTCTTGCATAATTCP-AATCT ATGCAAGAATAAT GC-MJAAAAT AA CAA G G CAAAAAGC- CAG G TGAAGC AG TAGAAACAAkT TATAAA;AGAT GTT TTAZGGAG'CAA ATGTTGAAAiC',(-CACAGCTTTA GTTACTTATGGTTCAGATATTTTTGA TTGGAAGCACAkGTT A.AAGTTATA.A.AAGGTTTTkAQAGGATCCTTATTAT(GCTTGAACTAGT TTCAC-AGTTCAGACAAATGAT 4 ATAGCTATAAAAAGTT S CT-,AATATTGCTGCTGATATTATAAMili.AGATCCCTAM GAAiGCTCCAGMIGCT 10 AAG;TGGGiGGGA;(C-D-AAG2TCTAGGATTAACTCCAGAAkAAAAQm.AGGGAA3TATGATTTA AGTAAGTAGGTGAZG ACCTTTACATGAF GCTTTTATGGAGGCG ATCCTTGTTAGTATATACAGCTAGAGTAPIUAGATT nTTGTTCATCTAA CTGACGTTTCCAACAGATCATATGCCATTATAGTTTTGT~fAAAGGTTCAtACATAC GCAAATC-AATTTGAGAtLGATAPAUGAAAAACGT TAT TTAGACAAPAATAAT TATT TTATPACTATGATCCA GAA. -iAnTCAAAGGCAATGGGG-AGf AGTTACTTTXTTGTTTCFCTPTAGCATAGTTATCAAAC'ACAG3ATAAkTTTCT 15 GGtA.4ACTTzAA-AMACTTCATTATTTAGATTTAA ATCTTAATTACCCTAAAGGTACA_;ATTTATAG.AAATGGn CCAGTAAG-AGA ,ACATGGAACACCAACCAAAiCTTTATATAAATAGTTTAAAACAGAAAAiATTA'TG ACATC-TTT ~ATTTTGGTATAGATATATCTQGTTTTAGACAAGWTT.KAA~ATGAGGATTATAAGAAk AAhTC-Ai2GAT-GGTAGT TT--~.TCAAATTGAAGG AGGTACTTTTGAACTTTCA(IATGCGATAAQAGP CAACTAA TG-AATTCATTCTCTF TCTAAAV-CCTGAG TATTATACCCCGZTAGTAACTTC'AGCTGATGTATQTA ATA ATGA-ATTTTATCTAA- tATT 20 FCA-.GAACAAT-TTGA.AAGA'-TTTTAACAAAGMAzACTLCAATTGTTAATGA.2ACT-AWAG AAGATCCTATGGGT F FGATAA&1-LATCAATTTACATCT TGGCAAPCGG ACAAkACATTGCAA'CCAA,'GTGATTATA CTTT CAGGGAGA2 ,Tt FGGAAGCTATTAAA -GTAGC' TGCAACTGAGGGCCTAiTAT;ATGG TGGGATACTTAAGGGGT-TAAAP FTTAGAATnCATC3.AAATAAACTCTA-GTTAGZ'GTTTG',ACTTAGGGAGGGGCAAAA~nAGTIAACAG-TCACA 1 TATQATGT-GAA-ACTAQ.ATGACAC-TTTTATTA2TAACAAAPTTCTATG C.ACTrATGGTAGAAtVCAA CATTGAA T 25 CCTAAATCAGAGGAACCCGATACAC(TTAG SGkTTTTCCAATCCCTAAJATTCGTG ATGTGA(;AGA.ATATCCT AC7AATAACGATTAAAAACGzAGA;AGAAGTTA.rG'-TGAAATTGAATTTACA.AA-AGTTGTA.UfGAATAATAATAA-G T'NCTTCTCAAGG AGCTACATTTGAACTTCA.A GAA-TTTAATGAAGATTATAAACTTTA" TTACCAATAA A AATAATAAT TCA.XkAGTAGTGAkCGQCAGAAAA.CGGQWATTTCTTAQMAQATVTTGAAAGATGGCAAkATAT CA'GTTAT-AGAA GCArGTTTC*3CCGAAGGATTATCA-%2iTACTAATAACCAXTTTTAACTTTT-AAGTT 30 GTTAi AAACGATACAAA tATATAZATAGCTGTTAATAACAATTTC TGAATAT CATGAGGAAG*TGAAAG CATTTAATTACCAACAC, GCATATTCCACCAP3kAG(l -rAATTATTCGATGACAQ GTGGGAAAGAATTCT'ATCT TT C AT TTThA\TAG GTrGGAG CTA TG A TGT C TA T TCAGGWTG GPAT TTATUT TWGGAAAAjG ACA T UAAAATC T A GTGATCAT CAAT CGAGAA.AGAT TV ORF amino acid seciuence (SEQ ID NO: 185) 35 M I'K KVlTTEVTGEATFDNLT PGDYTLSEETAPEGYKKTTQTWi QVr iVESNGKTT IQNSDOES IT X1QPQE LDKQYP LTGrAYEDTKESYNLEHVKNSIPNGKLEAYAVPYSSEGEHIREIQEGTLSRRISEVJNDLDHNEYKIELTVSG EI KGFKEDPYYOLETSFTV. TNDY.SYKKFTN IAADI I KR FKEAPEAKNGOTSLGLT PEKKREYDLSKViGE 40 TFTMKAMlEADTLLSS ORKSPEKI iVNLTDGVPTRSYAINSFVKGSTYANQFERIKE-KGYLDKNNt-YEI T DP SKI KGNGESYFLFPLDSYQTQI ISGNLQKLNYLDLN LNYPKGT I YRNGPVREXGTPTKLY INSLEQENYDI F NE-GI DI SGF~RQ*VtNEDY'KKNQDGTF-QKLKE'EAFELSDGSE I TEL' fNSFSSXFEYYTFIVTSApVSNNzI LEE! QQQFEKI LTKENS IVNGT'IEPGK-LLNQLQS'TQNG MD ITGN G EV LEYIKNKLYVP.,GLNLGEGQKV'-TLTYDVKLDDSFI SNKFYDTNGRTTLNPKSEEPDTLRDFPIP: IREYP 45 TITTESELGE 1 EFTKVDKDRNfKLLLKGATFELQEFL14E-DYKLYLP IKNNNE NKVVTG-ENGKI EYKDLKDGKY FILGGA 2k SIA2GGTYIWKRHIKK;SDAS fIEKD Strain SAA23 50 ORFLDNAseuec(SEQ ID NO: 205): ATGAG.'AAAPATAGCAA2 AAA-ITTTTCTAM, ATATTGAGGTTAAGTGTTTTTTGTTTGTGCAAA.TACG .,WAAT A'CC2aATGTTTTAGGGGAAAGTA02CGTA CCGGAAATGGTGCTAzGGAAA"GTTAGTTGTTTAAAGACACAT GACCAG5AAC; AAACCACTT-TCAXAAGCTACCTTTGTTTTAAAACTGTCCTCATCAA AGTAAATA AA .AAA SGTAA CTGCTGAGC LzAAnGGTGAAGCTA CTTTTOGATtA1TCTCATAGGTGGAkGATTATACTTTAT CAGAA 4 55 GAAACAGCGCCCGAA GGTTATAAAAGACTAACC-AGACTTGGQ AAGTTAAGGTTGAGA, GTAATGGA.AAALCT AG-GATACAAADATAGT'-GGTGA34TAAAATTCCACA ATTGGA.CAAATCAGGAAGAA %CTAGATAAtGCAGTATCCC CCCACAGGAATTTAT4GAAGAT ACAAAGG-AATCTTATAA.AOfTTG AGCATGTTAAAsGGTTCAkGTTCCAAALZTGGA AGTCAGAGGCiVtJ&A GGAGTTAACCC-ATATTCAAG TG-AGGTG AGCA'TATAA2GkSAAATTCCAGAGG-AAGA TTATCTAAAGGTATTTCAGAAGTAGGTGATTTAGCTCATAA-XTATATAAAAITTGAGTTAGCTGTGAGTGGA 60) AAAAPCCATAG T;AAAACCAGTGGACAAAC-AAAAGCCC-GTTAGTGTTGTCTTC'GTACTCGATAATTCTAA2%CTCA ATGAATAACGATGGCCCAAAT -TTTCAAGGCATAAAAGCCAGA-AGCTGCC3AAGCTCTT2GGACCGCA GTb-AAAGATATTTTAGGAGCZAA4ACAGTG'CATA. TAGGGTTGCATTA14GTTACCT ATGGTTCAIGA .TAiTTT TTGAT GGTAG-GAGTGTAGATGTCGTAAAA GGATTTAAAGAAGATGATAAATATTATGGCCTTCA2AACTAAGTTCA.CA ATTCAGACAGACAATTATAGT-CATAAZACAATTAACAAATAATQCTG-A.AGAGATTATAA $AAAGGATTC-CGA.CA 5 GAAGrCTCCTAAGCTAAGTGGGGATCTACTACCATGATTACTCAGACACA AAGGA GTAC-TAT4CTT AGTAAAGTAGGAGAAA-CATTTACTATG~tAAGCCTTCATCJrAG' GCAGATGATATTTTGAGTCAAGTAAA.lTCGA AATAGTCJAAAA~zATTATTGTTCMAGTAACTGATGGTGTTCCTAGGAGAT(ZATATGCTATTAAI-TAA2 TTTTA, CTGGG TGCATCATATGAAAGCCAA7TTTGAzACAAATG?2A' AAATGGATATCTAAAPTAAAAGTAATT TTCTA C-TTAC-TGrATAAG,-CCGAGGrAT-rTAPAAGG7CAAAtTGGGGAGAGTTACTTTTTGTTTC-CCTTAGATAG,'TTATCAA 10 A CACAGATAATCTCGTGGAAACTTACAAAAACTTCATTATTTAGATTTAA ATCTTAATACCCTAAA GTACAr AATTATGACATCTTTAATTTT-GGTATAGA TATATCTGGTT-TTAGAC6AGTTTATAATGAGG-ATATAA 'GAA% AAkTGAAGAT GGTACTTTTGAAA ,AATTGA.AAGAGGAAG7CTTTTGAA2CTTTCA ATGGGGAAA'TAACAGA2PCTA ATGAAGTCATTGTGTTCTAAPACCTGAGTATTATACCCCGATAGTAACTTCATCCGAGCAT -CTAACAAGCAA 15 ATTTTATCTAXu T TCAGCAACATTAAAATTTTACAAAGAAACTCAATTGTTAATGGAACTAT GAAGATCG TA T GGGTGACAAAATGCAAT TTACAG CTT7G GCM'AC GGCACAAAC AT T GAACC AAGTGAT TATAG T TTACAGiGGAA,4ATGATGGA AGTAI TAATGAAA . GATAGCIATTGCAACTGGTGGGCCTAAZTAATGATGGTGGAATA CTThAAGGGGTTA ATAAPATAATCA.AAATAAA-TC'TACGTTAGAGTTTGAATTAGGGGAGGACAAI% AA-AGTAAGACT-CAGATATGATGTGAAAGTAGATGAQAGTTTTAz TAAGTAAA.AAzITTCTATGACACTAA'GGT 20 AGAA CAAC-ATT4GAAT CCTAAPATCAGAzGGATGCTAI A--CACTTAGAGATTTTCGA"ATCCC-TAAAs-ATTCGTG-AT G TGAGAGAAT ATCC TAGAA TAAC GAT TAAA-AACG'AGAAGAAG'1'TAGGGAJT GAXT T TACAAAAG T TGA? A.%,GATATAATAATTGCTTCTCAAGGAGCTACGTTTGAACTTCAAGATTTAATGAA sGATTATAAAkCTT TATTTACCAATAAAIL k TAATAATTCAAAzAGT AGTGAJGGGAGAAAAC(GCAAAsJTTTCTTACAAA2GATTTC AADAGATGGGAAA)STATCAkGTTAkATAGA AGCAGTTTCGCCGAA-GGATTATCAAAAAlATTAG.TA.ATAAi.ACCAMZ.T 25 TTAACTTTTGAATGTTGTTAAAGGATCGATAGAAZAATATAATAGCtVGTTAATAzhACAGATTTCTGAATATCAT GAGGAAGGTGAC -AAGCATTTAATTAQGAAC.AC-GCATAT-TCC.ACA-AAGGAATTATTCCGATGACAGGTC GG AAAGGYAATTCTATC'TTCATTTTAATAGGTGGYATCTAZ TGA) TGTCTATTGCAG-GTGGaATTTATA TTTGGnAAT AGATATAAGAAATCTAGT.ATATATTAGAG-AAAAGATTAA ORFamno.acd ecq.unce (EQID NO. 186) 30 MRKYQKF7SKI LTLISLFCLSQI ?LNTNV,-LGESTVPEGAKffGKLWEKYTDDQNKPLSKTV LKTTAMPE -AI E KVTAELTGEATFDNLI 2GDYTLSEETAPZGYEI{TNQTWQVRVFJESNGKTT -NGKST GNELKY PTGI YEDTKE SYKLEHVEGSVPNGKSEAKAN PYSSEGEE IRE 1PEGTLSKRI SEVOlDLA.NEYKI ELT VsC KTi-VKPVDKQLDVPJfL~DSSMNNDGFNFQHNtKAKAAEALGTAV11KDI LGANiSDN RV7ALVTYG5JI 1FD GRSVDvVKGFKEDDKYYGLQTKF'TIQTEN4YSRKQLTNN4AEE 11 E'l PTEAPKAKWGrSTTNGLT PEQQ,,KEY YL 35 SKVGETFTMKAFMEADDI LSQVNRNSQKI NTlPR A NKGSEQEI GLKN LTDKPRDI KGtGESYFLFPLDSYQTQI IS351 LQKLRYLDLNLNYPKGTFYRNGPVREXGT PTKLY INSLKQY NYDI FUS I DI SGFRQVYN EDYKKNQDGTFQKLKEEAFELS DGE I TE L KS FSSKPEY YT PI VT SSDASN IF I LSKIQQQFEK ILTKEN,,S IVUS T IEDPI'IGDKI NLQLGNGQTLQPSDYTL QGNPGSIT1KDS IATGGCPI4ND' ; I KGVKLEY IKNKLYVRGLNLGEG3QKVTLTYD)VKLDD)SF1 SNKFYDTN-GRTTLNPKSEDPNTLRDFP IPFEI D 40 VREYPT ITT KNEKELGET EFTKVDKDNNKLLL;KGATFELQEFNEDYELYLPI KN4NNSKV VTGENGE ISYI-DL KDGKYQL IEAVJSPKDYQKI TNEP ILTFEVVKGS IONI IAV{TKQISEYHEEGDKNI U-T IlPPKGI I4TGG KGILSFILGGSMM1SIAGGIYINKRYKKSSD.SR EKD Strain IC98 45 ORF DINA sequence (SEQ I-D NO: 206): ATGAAAAAGAG%AAAAAAATATGGAGAGGGTTATCAGTTACTTACTAATGGTGT'CCGAAATTG(-CAITh SC £ ATATTGGTACAAQ."GTGAACOCAATAGATCAGACTGAXGT TGT TAAUJAA GGGAGmZA C AATGCTAC-ACCA 1TTAGGCAA'AGCC-ACTTTTGTGTTAAzAATGAJATGAT2AGTCAGAM4GA'.AGT(-GA A ACGGTAGAGGGTTC TGGAG^AAGCAAlCCTTTGAAAA-tCATPAVAACCTGGACACrTACACATTAAGAC-AAGAlAA 50 GCACCAAT TGGTTAT ThAAA1' CTGATAAACCTG.AAkAGTTAAGT TGGAGATAA7 CGG AG.CAA.CAkATAkPJ C OASGG-TATGGATGCAGATAAJAGCAGA.GAAAC-AAAAG.AAGTT TTGAATGCC-CAAT ATCCA2%AAATCAPGG T MT TATGAGGATAkCAAAkAGAAA'tATTACCCA TTAGTTAAUTGTAGAGrGGTTCC,AA TTC-GTGAAC-AA TACAAAOCC TTGAATCICAATAA zTGG.BAAAGATGGTGGGAAGAG~TTGCTGAkAG-TTGG-TTATCSI'AAAA%.A,-TAGC GTCAATGATCTCG7ATAAGATGAATATATAATT'PATACTGTTGAGGTAAACCACTGTTGJXACGAAA 55 GAACTTATCA.AGGACTAGATGTCGTTGTGCTATTAGATAATTCAA%-ATAGTATGAATAATGAAA GAG-CAM AATTCTGAA6PAGGATT?,AAAGCTGGGGAAG CAGTTGAAAA7 GCTGATTGATAA-?AATTACATCA%ATAAA -GA( AATAGAGCTAGGTCTTGTG ACATATGCCTCAACCATTTTTATGGTACTGAGCGACGTTCAAGG(,AGTT GC-CGATCAAA-ATGGTAA JAGGGCTGA ATGATAGTGTATCATGCOATTATCATAAiAACTAC'TTTTA CAGGAArCT AC-ACATAzATTAC-AGTTA TTTAAATTTAACAAATG.TGCTAC,-GAGTTAATATTCTAAAGTC.A AGAATTCCAI 60 AAGGAAGCGGAGGATAAATGGGGATCGQACGQTCTATCAATTTGGTGCG ACA TTTAPCTC?-AAAAGC- TGTK -. 0

ATAWG

4 CAAAWI.GAATTTTAGAG- ACACAAG2TCTAATGCTAGI3A-AAAA',ACTTATTTTTCA- CGTAAk.CTGAT GGTGTCCCTAJ3GATGTC-TTAT GCCATA-ATTTTAAT-CTTATATATCAACATCTTACC--AA CCV3TT TAAi TC'TTTTTTAAATAA-AATACCAGATAGAAG TGGTATTC'TCCAAGAGG ATTTTATAATCAATGGTGATGATTAT CAAkATAGTzAAAGGcAGATI GGA:GAGAGTTTTAAAPCTGTTTTCGGATAGA'%AAAGTTCC-TGTTAC'TGGAGG-AACG' 5 ACACAAGCA GCT'TATCGAG TACO-GCA AAATC AACTCTCTGT AATGtGTAATGAGVGGATATGCAATTAATAGT GGATATATTTATCTCTATTGG~AAGA TTACAACTGGGTCTATCCATTTG TCCTAGCAA.GAAG(TTT CT GCAACGAA-kACAAATCAAAACT CA TGGTGAGCCAACPACATT ATACT TATGATTAGCTA TATGACATTTTTA CTGTTG GGATTG GTGTAAACGGAOATC-CTGGTG CAACTC-CTCTTGAAGCTGAGAA~t4TTT ATGCAATCAATA.TCMAGTAA-AACAOAAVAATTA TACTAATGTTGATGA.TACAAATAAAA5TTTATOATGAGCTA 1 0 AATAAATACTTTAAAA-CAATTGTTGGrAAA-AACATTCTATTGTTG~ATGGAsAATGTGACTGATC-CTATGGGA GAAGTGS.TCTAT'siiTGI-VIGTTAAA~.",GTAGTTGTGiTA GGCAGT CAATT.AAAAAATGGT GTGGCTC2TGGT"GGACCAAAlCAGTGA TGGGGGAAT-ITTTA7AAGATGT TACA GTG ACTTATGATAAGAQ, ATCTCAAACCATCAAAATQAATCATTTGAACTTAGGA,'AGT,-GAC,'A-AAGTASTT OTTACCTATGATGTACGTTTAAAA GAT AACTATAT-,ASTAACAAA TTTTACAATAOAAATAnTCGTAO.AAz. C 15 CTAA GTCCGAAG AGTGCAY AAASACCAA- ATAC2TATTCGTGATTTCC-CAATT CCAAAATTCGTGATGTTCGT GAGTTTCCCGTACTAACCATCAGTAATCAGALAGAA-AATGGGTGAGGTTGA.ATTTATTPAAGT'-T~A.ATAAAGCAC AAA2sCATTCAGAATCOC TTTTGGGAGCTAAG TT £ CAACTTC-A3ATAGAA?.AGA.TT £TTCTGGGT ATAOCAA TTTGTTCCAG AGGGAAG'TGATGTTACAACAAGAAWATG-GTAAAATTTATTTTAPLAAGCAC-TTCJCGATGG T AACTATAAATTATATGAAATTTCAAGTO CAOA7TGGCTATATAOAGGTTzAAA.ACOAAACCTGT TGTGACATTT 20 ACAATTCPAAz TGGAGAAG'TTACGACCTGAJSCAG~e ATCAATCATAAAAATCAATCGGGTATCTT GAAJ GAAATGGTzAAA.CATCTTATTACOAViACtTrCCAAOGCCCACCAGOTOTTTTTCCTAAA CAGGGGGAp ATTSGTACAATTG TCTATATATTAGTT-GGTTCT.ACTTTTATC .kA-TCTTAC-CATTTGrTCTTTOCGTCGTAAA., CA-ATTGTAA 04W amino ,acid zaluence {8EQ, Irl NO: 2187) 25 MKK QKIWRGLSV.TLLI LSQI PEG! LVOG>7 TQPT',JOALGKV1 VRKTGDN AT PL-GKATFJLrTKNDNDKSETSNE TVEGSGIFATFEN IKFGDYTLREETAP IGYKKTD{TWKVK'VADNGAT II EGNDADKAEKRKEVLN. QYPKSAI YEDTEENY ?LV'NWEGSKVGEQYKALNPINGKDGRRE IAEGWLSKIITGVNl~DLDKNKYK IELTVEGKTTVETK ELNQPLDW VLLDN SNSMNNERANNS,,RSALKAGEAV7ELIDE I TmSNKD Rv ALV7TYAS;TIEGTEATVSKGV, ADQNGK;nL DSVSWDYRKTTFTATTHNYSYLNLTND.ANEVI LKSRI PEEI NGDRTLYQFGATETQKAL 30 MRANEI1LETQSSNAP&U<LI FHVTDGVPTMSYAI-NENPYI1STSYQNQENSELNKI PDRSO LQEDEIIiNODDY O 1VKGDGESEKLESDRKVPVTGGTTQAAYRV PQNTQLSVNSNEGYAINSGYIYLYWRDYNWVY~rPEDPKTKKViS ATEQI ETHOSPTTLYENIGN I PEGYD! ETVGIGVN,.GOGAT PLEAEKEMt~QS1-'SSKTENqYTNVDDTNKI YDEL NEYYFET IVEEKIS IVDGNV'.TDPMGRMI EEQLKNsGQSE. TIDDYVLVGT(NDGS'QLRNGV7ALGGPNSDO.-GI LEDYT V TYDRTSQT I 1INHLNLGSGQK-VVLTYDVIRLKDNY1 SNFEYNTNNRTTLS PESECE NT IROE I PKIRDV R 35 EFPV-ILT ISNOERMOGEVEFI KVKDKHSESLLGAKEQ.LO1 EKDESGYKQFVPEGSDVTTKNDG I YEKALQIx; NYRLYE ISSPDGY1EVKTKP'VVT"FT IQNGEVTNLKA-DPNANKNQ IGYLIEGNORH I TNT PKRPFGVFPKTGG IGTIVYILVGSTEMTLT£OSERRKQL Strain 0C105 ATGAGAAA7,ATACAAAAATTT GTAA.ATATTGAG-GTTIAAGTCTTTATTTGTTTGT-CGAATAO'CGGTTAA. T ACCAATGWTTTAGGGGAAAGCTACCGTAGCGAAAATGGTGCTAA -tGG AA-AGTTAGoTTGTTAAPAAGACAG-AT GACCAGA-;ACAAACGAG-TTTCAAAAGCTACC-T- TG.TTTT.AA %AATATGCTATGA-AA ,GAAATAGAAz AAAG -TAACTGCTGAGG TAACA GGTGAAG CTACTTTTG ATA ATOTGCAG.-CTGGAGA$TTACACTTTAGf-AGAA 45 GAAA.CGGCACCCGAAGGATACAAAAAL~GAO'IACCGAGOAC TTGGCAAGTTAAG GTTGAiGAG'TAA LGGAAAAA,7CT CT TACAGSAG-CTTA TGAAGATACAAAAvjGAATCTTATAATCTTGA CATGTTAAA, AATTCAATTCCAAATGGG A.AATTAGAGG CAAAAG-,'CAGTTAATCC-ATATTCAAGTGAAGGTGA(C CA TAG AGAAATTAAV GAGGGAAP.CAZ TTATOTAAGTATTTCAGAA %GTAAA'TGATTTGGATCATAA'TAAATATAAAATTGAGTTAACTGTTAG CGGT 50 AA ATOCATAATA~AAACTATAAA TAAA,;GATGAACCTCTG-GATGTTG3'T~TTTGTXTCTTGCAT~ATT'GAAATTCT A TGAAGAA TAAT GGA.AAAAATATAO AAG GCAAAAAAGG C AGG TGAAG CAG TAGAA ACnAT TATAAAA.G ATCT T TTAG GAGCAAJ'VIGTTGAAAOCCGAGCAGCTTTtGT TAO TTATGGTTCAG-ATATTTTTG ATGGAAGG4ACAG TT A.AzAGTTATAXRAAGGTTTTAeGAGGATC-CTTATTATCFiACTTG AAAOCT.AGTTTCACAG TTCAG-ACMAzTG7AT TATAGCTATAAAAAGTTOACTAATATTGOTGCTGATATTATAAAAAAGATCCCTAA2AGAAGCTCCAGAAGCT 55 AAkGTGGACSGGGGACAATCTAGATTAACTCCAG-AAAAAA AGAGGGAATATGATT4TAAGTAAAGTAGGTGAG ACCTTTACAATGzARPAGCTTTTATGGAGGCAGATAGCTTGTTAtAGTAGTTAC, 'GCGTAAGTAAyAAGAlTT ATTGTTCATCTAACTGACGGTGTTCCAACAAC-ATCATATGCCATTAATAGTTTTGTAACAGGTTCAACATAO GCGAAATCAAT TT GAGAGAAkTAX4GAhAGGT TAT TTAGA CAAAATttT TAT TTT ATAAC TGAT GAT CC A GAAAA"z.GATCAAAGGCAATGGGGAGAG TTAO,'T'TTTTTTCCCTTAGATAGTTATCAAACACAGAlTXTTTCT 60 CGPIAPC CTTACA3kAA,-CT T CATTAT TTAGkT T T AA C TTAAT TAOCC TAAAGGThACAAT T TATA GA.T GGA CCAG'TPAAGA~,ACATGGAACACCAACCkAAACTTTATATAAkATAS-'TTAAA.PACAGAAAAATT;,ATGAC-ATCTTT AAT TTTGGTATAGATAT AT CTGGTTTTAGCAAG~TTT ATAATGAGA,,'TTAT AAAAAATC,7AGATGGTA-,C2 TTTCXAAAAXTTGYAGGAGGAAGCTTTTGAACTTTCAGATGGGGAAATrAACACAACTALATGAATTCATTCTCT TGTAAIACCTGAG/ TATT ATACCCGATAGTAACTT"CGCTGATGTATCTAAT AATGAAATTTTATCTAAAATT 5 GCAGQCAATTTGAAAACGAT TTTAACA2UGG2JkAAC TCAAT TGT ThATGG.AC-TATAGAAGATCCTATGGGT G CATAAAATCAATTTACATCTTGGCAACGGiACAAA.CATTGCAA CCAA.GTGATTATACTTTACAGGGAAjATGAT I GGAAGTATAATGAAAGATAGC ,ATTGCAACGGAGGCCTAATAAT GATGGTGGG ATACTTAA' AGGGzGTTAAA 1 TTAGA ATACATCAiAAAATAAACTCTACGTTAGAGGTT4TGAACTTAGGGAGGGGCAAAAGTAACACTCACAz TATGATGTGAAACTAGATGAC-AGTTTTATTAGTAACAAATTCTATGACACAATGGTAGAACAACATTGMXT 10 CCTAkATCAGAGGAAC-CCGXTACACTTAGAGAT.TTTCCAATCCCTAA AATTCGTG.ATGTGAGA.GA.ATATCCT ACAATAAC(-GATTAAA -ACG-AGeAAG'AAGTTlAQGTGAAZATTPGAATTT-ACAAAAGTTGzATA'AAGATAATAkATAAG TT4GC-TTCT,-AiAGGAGTCATTTGACTCAG(AA TTAATGAAGATTATAA'%CTTATTTACCAAi-AAAA A . TATATTCAAzPAGTA GTQ ACGGrGAJ&z GGcATTTCTTCPAAGz'tPATTTrAAGfAT(3CAAA'TAT CAGTTAATACA.AGfzCAGTTTCG 'CCGAAG GATTATCA.PAAAATTAC TA.ATAkA2' CAATTTT-AAC TTTTGAAGVTT CATTTAA .TTACAAiCACGQATATTCCACCAAM AGGMr,!TTATTCCGATCCGGTGGGAAkAGGPATTCTATCT TT'CATTTTAATAGGTGGAG CTATGATGTC TATT GCAGGTGGAATTTATTTTGGAA-lAGACATAAG-AAATCT AGTG-ATGCATCAAzTCGAGXt'AAGAtTTAAPJ ORF amino acid._ eqnce (SEQ I D NO: 1886) zO RI{QRFRI TLSFCLQIPN LGESPFEOA (GLWRJKTDDQNKPLSKATPJLKTTA H PESRIE KVTAESVTGEATFDNT'PGD)YTL SEETAPEGCYKRTTQTWQVKVr~ESNGKTT TQNS ,DFS II EQRQ-:ELDKQYP LTGrAYEDTKESYNLEHIVNS I PNSRLEAF- fl4PYS-SEG-EH IRE IQEGTLSRRI SEVU,,DLDE:NKYRI EL'TV SG JEI 1 T INRDEPLDWF -- VLDNSNSMNNG4"K tIFAFGEAVIET 11 DVJLSANVPENRAALVTYGSDI -FDGRTV 1(J RGFKEDPYYGLETSFT-VQTNDYSYRRKFTN IAADI I KRI PEAPEAKWOGTSLGLTPERRREYDLSKVGE 25 TF7TNRIAFMIEADTLLSS IQRKSRKI IVHILTDGTVPTRSYAINSFV!TGSTYANIQFERI RSFGYLDRNNYFJTOOD SRI RGNGESYFLF'PLDSYQTQI I SNLQRLH'YLDLNLNY PROT IYRNGPVREI4OTPTKLY 1 NSLRQKNYDI F QQQFEKI1LTRENS IVECYT IEDPNGDRJ NLXLGNC-QTLQFS DYTLQSRDOS lORDS IATSGPNNDGGGI LKEOVE LEY 1 RNKLYVRGLNLGEGQRPtT YDVRfLDSF-I SNKFYDTNIGRTTINPRSE'E PDTLRPDFPJ.PR RVREP N0 TI T INEFFL'S I EFTKV7DKDNNR'LLLRGATFELQEFNIEDYKLYLPIXRNNNSFVIVTGENGRI SYRDLRDORY FIL100AN44IS!AGGJYIWe RRWRSSDAkSISRD Strain MC108 35 RDNseune(EIDNi28: ATG;ALA.rAGACAAAAAATATGGAG-A-GGTTATCAGTTACT2TTAC,-TAATCCTGTCCC.AAT'TCCATTTGGT ATATTGGTACAA(GGAAAGCCAAGr-ATACCA ATCAAGCGAO'-TIGGAAAAGTl3-AATT.GTTAAAAA ACGGGAGAOr ?JTGCTAOACCATTAG-GCWGCCATTTGTGTGTAA-.AATACAlTATAAGTAGAAOAAGTCACGAAk ACGGTAGAGGS TTCTGGAGAG.%.'CAOCTTTG~ AAACAT-AAzACOTGGAG' CTCACATTArGAGAIGAAACA 40 GCACCAATT4GGTTATAAzAA!CGATAA-ACCTGGAAGTTA..GTTCAGATA CGGAGCAACAATAA C QACGTATGGATGCAG' TAA, GCAGAGCG2A ACGVtAGTTTATGO.,TCCATATCCAAATCA CTATT TATGAGGATACZAAMtGAAAATTAC-CCATTAGTTAA.TGTAGAGGG3(T TOG kAGTTG3GTGAACA!,ATAOAAA.tiGCA TGAATCC-AATAAATGGAAAAGATGGTCGAA GAGAGAT TGCTGjAAGOTTGGTTATCAAAAA ,AATTACAG(G GTQAA-TGATCTCGATt'AQAA-T.hAAiTATAAAA'IlTTGXATTAAOTGTTGAGCGGTA AACAG17TGTTGAAAJGPAA 45 C-AACTTAATCrAACCTAGATGTCGTTGTG C 'TTTAG ATAATTCAAATAGTATGAAsTAATGjAAA GAGCGAAT AA,"TTGTGA?.AG,-AGCATTr AGCTGGGAAGCAG,-TTG2AAAAG CTG7ATTGATAAAA' TTACATCAJ2ATAtAGAC A.ATAGAGTAGOTGTTCTCACATATGGO"TCAA %COATTTTTG:ATGGTACTGAAGCGACGGTATCAAGGG AGTT GGOGA 'TCPA3ATGGTAAGCGCTATGATAGTGTATCATGGGATTATATAA-ATA-TTTTACAGCAAG .T ACAGATAATTACAGTTATTTAAA--TTTAACAAATGATGCTAACGAAGTTAATATTTA-AGTIA; GAATTGGA 50 AA GG7AAPGCGGAGCATATAARTGGGGATC-GCACGC-TCTATCAATTTGGTGCGAGIrATTTACTCAAAAGCTCT A ATGAAAGCAkAATGAAATTTTAG7AGAG,-ACA-AYGTTCTA ATGCTAGAAAAA-,VAACTTATTTTTCACIGTAACTGAT GGTGTCCGTACGATGTCT TATGCGATAAA~mTTTAATCCTTATATATGAGATCTTACAAAG.CAGTTTAAT TOT TTT TTAAATAAA3TA-COAGATAGAAGT GGTATTCTOOCAAGAG GATTTTATAATOAA-?TGGTGATGA-TTA-T C7AAATAGTAAAAGJ- AGATGGAGA .,GAGTTTTA CTGTT-TTGGATA*GAAGTTOTGTTACGGGGAAOG 55 AO-AOAAGQ-A-TTATO GAGTAOCGOAAAATCAAOXTOTOTGTA.ATGAGTAATOAGGGA.TATGO3AAT.-TAA TAGT GGA 'TATATTTATCTOWATTGGAAGATTAOAP.tCTO-GGTOTATVCATTTGATCGTAAG ACAAGAAAGTTTCT GCAAGAAAOAA, %ATOAAAAOCTOA TGTGAGCAAOAAOAC ,TT A'.TATTT'GG;XAAA TAGACCTAAAG7GT TATGAOATTTTTAC-TGTT GGGzATTGGTGTAAA4CGGAGATCCTGGTGGAAOTCCTCTTGA',AGOTG3AGAAATTT A'TGCA'ATGAATATCA2lAGTPAAAGAAA 'ATTATACTA TGTTGATGATAC-AAATAAAATTTATGATG.AGOTA 60 AATM ATAOTTTAAAAQAC 'ATTGTTGAGGAAAAA.CATTOTATTGTTGATGGAAA.TGTGAOrTGATOOTATGGGA - 112 GAGATGAT TGAATTC CAAWTTAAAAAATGGTCAAAGT TTTCACACTAGATVWACGIZTTTGGT TGGAAATGAI., GGCAGTCA.AT TAAAAAA,,tTGGTGTGG7CTCTTGG GAG (CAAQCAGTG TGGGGGATTTTYLAAGATGTTACA, GTGACTTATGATA-AGA21CATCTOA.AACCAWCAAMTCA&TCATTTGAACTTA6GGAAGTGGACAAAAAGTKPGT'I CTTArCCTATGATGTA'CCTTT~AA-iACTTATAAGTAiCA.A'TTTTACAATACAATA TQGTACAviCG 5 CTAn.GTCCGAA'GA.G GAAAAAGAACttAATnCTATTCGTOATTTOC" CATCCCAAAA TTCGTGATOcTTCGT GAGT TTCC aGThC-TAACCATCA GTAAWtCAGMA.PAAA ATGGGTGAGGTTGAA7TT TAT TAAAGTTAATAAAGAC AAACATTCAGAATCG :CTTTTGGG AGCTAAGTTTCAACTTCAGATAAAAGA TTTTTCTGGGTATAAGCAA TTTGI7TCCAGAGGGAAkGTGA'IGTTACAAO~ AG ATGATGGTAAAATTTATTTTAAGz.'CACTTCAGATGGT AAC TATA AT TA TAT GAAATW7TCAAGT CCAGAT GGC TATA TAGA GG T TPAAGAAAC CT GT TGTGACAT TT C) ACAAT TCALAATG GAG AAG TTAC G PAACCQTCAGCA GATC C ATG CTAA TA.AATCA_?AT CG GGTAT C TT GAA GGAAATGGVTAAAC'ATCTTATTACCAACAC-TCCCAACGCCCC'ACCAGCTGTT TTTCCTAASAACAGGA ATTG-GT~r'ACATTGTCTATATATTAGTT GG7TTCTACTTTTA'TG ,ATACTTA CCAT TGTT'CGCGkA CAATTGTPJA ORE amiuno acid IDunc NOQ XL'1NO 9) TVEGSGEATFENI KPGDYT LREETAF IGYKKTDKTWKVKV' ADNGAT II EGMEJADKAEKFKEVLNAQYPKSA'I YEDTKE 4YPLVNVEGSI<VGEQYKALNFINGKDGRRElAEGWLSXK ITGVI4.$DLDKNIKYKI EIJTVEO-KTT VYETi< ADQNGwKALNDSVSWDYHKTTFTATTHNYSYLNLTNDANEV'N1 LESRI PKEAEH 1 GDRTLYQFGAVVTTKAL 20 LKANE ILETOSSNARKLl FRVTDGV',PTMSYAINWnPYI STSYQNQFNSFLNK1 PDRS(31 LQEDF1 INGODY QIVKGDGESFKLFSDRKVPVTGGTTQAAY.,RVPQNQLSVNSJE 2 YA1 NSGY IYLYWRDYLGVY PFDPKTKKVS ATKQIKTHiGEFTTLYFNGNIRPKGYDIFTVGIV2-4GDPGATPLEAEKFMQSISSKTENYT4VDDTNKIYDEL VTYDKTSQTIK I NHLNLGSGQKVV LTYDVjRLKDNYI SN: .FYNTNNRTTLS PESE £ PNT IRDE-PJ PKIRDVR 25 EFISVL.T' SNQR Kt4GEVEFl KVIDKHSESLLGAKF QLQI EK DFSGYKQF-VPEGSDVjTTKNDGKIYFKALQEX; NYF,,LYA 1 ST XYEVETI PVT FT IQNGEV',rITADNNINIGYLEGNGKN LI TNT PKRF PGVFPKTGG 1TGW IVY ILVGSTFMI LTICSFRRKQL Strain 1C216 30 ORF DNA sequence (SEQ ID NO: 209): ATGAA,%AAGAGACAA4AAAATATGGAsGAGGGTT-ATCA~GTTAOTTTACTAATOICTGT CCCAAATTCOAT TTGGI ATATTGGTPAAGGTGAAA-CCAAGATAOCAATCAACCACTTGG AAAAG,,-TAATTG TTAAAAAP- AC.G7GAAO. AATGCTACkC'CATTAGGCAAAGCGACTTTGTGTTAAAAkTACAATATAAGCAAAC'ATCACG-ZA. ACCOT. GAGGOTTCTGGACAAGCAACCTTTC AAACAT!' AAACCTGGACkACTACACATTAAGzAGAAGAAA CA i5 GCACCAATTO"GTTATAAA!,VAACTGATi AAACCTGG-kAGTTAA71AGTTGCAGATAACGGAGCAACAATAAT GAGGCTATGGAT GOAGATAAA;%GCAGAGAJ& ACGAADAAAAGTT TTAATGCC"CAATATCCAAAATOAGOTATT TzATGAGGATA CA.Al~'AAGAAAATTACCCATTAGT'TAATCTAGAGG GTTCCA~zAGTTGGTGAACAATACA-,AAGCA T TCAATOOAAVTAAAiTOG iAAAOATIGOTCCAV-AGCAOATTGCTGAAOO-TTOG-TThT'-CA^-!AAAATACAOCGG GTCAATGATCTCGATAAGA.ATAAATATA-AAWTGAATTAAOTGTTGAGGGTZ'JUAACCACTGTTGAAAC,'GAAAZ 40 GAACTTAA TQA-ACCA4TAGATG;TCG TTGTGOTATTAGA'TAAZTTCAAAT. CTAT CGAA)TAATG AA.rGAOOCtAW AAWTCTCAAlAGAOCATTAM-,AGCTGGGGAAGCAGTTGAAAGCTGA~TTGATAAM-ATTACATCA.ATAACAC AATAGAGTAGCCTCTTCTGACATATGCCTCAACCATTTTTGATGGTACTGAACGACCGTATAiAAGCGGTT GCCGATCA? TGGTAAGCGCTGJ TATATGTTCTGGGATTATCA.TMJ'%.CTAZCTTTTACAG CAA.CT ACAOAATAATTA %CAGTTATTTAATTTAACAAATGATGCTAQGAAGTTAA.TATTCTAA.AGTCAOAATTCCn 45 AAGGAAuzGCGGAG CATATAA7 ATGGGG3TCOCACGCTCTATCAATTTCGTGCG7ACATTTACTCAAAALAGCTCTA ATGAAAGCAAATGAAATWrTTAG2AGACnCAAA3T TCTAATGOTAGAAAANAAnCT TAT TTTTCACGTAACTGAT &GTGTCCC-TACCATGTGTTriTGCCATAAA- TTTTAATCCTTATATATCAACATCTWACCA-AAACCAGTTTAA4T TOTTTTTTAATAA-4ATACCAGA-; TAGAAkGTGGTATTCT0CAAGAG,-GATTTTATAAkTCA ATGGTG AT AT TAT CAA; ATAGTAAAA%?,GGAC.ATGAGAGAGTTTTAAzACTGTTTTCOGATPAAAACTTCC-TOTTArCTGGAGCAACC 5 0 ACACAAZGCY AGCTTTCGAC TACCGCAAAA TCAACTCWCTGT-AATGAG7TAATG-AGGGAkTATGCAATTA %ATAGT GGATATATTTATCTCTATTGGACAGATTACAACTGGGTCTATCOATTTGATCCTAGACAAAGAAAGTTT CT GC-AACG-AAAC,-AAATCA,AAAOCTCATGGTGAGCCAACAACATTATACTTTAATCGAA'ATATAAGvACCTA AAGGT TTA C AT TT T TA C T GT T G rA TT G GTG TACG G A GI%7CCT G GT G C1-kC TC C TC TT GAA GC"T G;AGAA.;A T TT A CCA.ATCAAiTATCAAGTAAAAO-ACAAAkATTAkTACTnAirTGTTGATOATACAA.l AT~kt'ik TTTATGATGX 5 00TA 55 AATAAATACT TTAPAJACAAkTW GT TGAG GAPJAAC AT TCYAT T G TTGATGAAAWGTGACTCGAT CCTAT GGGA CAGATGATTGAA TTCOAATTAAM,;AATGGTCAAAGTTTTACACATGATIGATTACGTTTTGGTTG~GA;%ATG;AT GGCAGTCAAITTAAA-AAATGGTGTGGCTOTTGCTCGAPCCAA, ACAGTGATC3GGCGM.TTT TAAAAGzATGTTAICA GTGACTTATG,-ATAAC-ACATCTCAA ACCATCAA.AATCAATCATTTGAACTTAGrGAAGTGGACAM\A'L ,AGTAGTT OTTACCTATCATGTACGTTWAAA.AGATALACTATATAAPGTAACAAAVTTTTACAATACA AATA.ATCCTA-AAC-G 60 CTAAGTCC-GAAGAGTG.AA2 PA'GAACAAAACTATTCCTGATTTCCCAATTCCO-AAaA TT CGTGATGTTCGT GAGTT1'TCCGGTACTA ,ktCAT cAGTAAT CAGAA4,GAAAATGGST GAG GTTGAATTT AT TAAAGT TAATIAAAGAC TTTGTTCCAGAGGGAAGTGzATGTTACAAC-AAAGAATGATGGTAAAATTTATTTTAAAGCACTTC-AA A.TGGT i AA CTA TMA TTATATGNAiTTTCAAGTCQAGATGGCTATA TA AGCTT2,AACG A A-CTGTTGTGACATTT 5 ACAtTTCA.AAATGGAGAAkGTTAC"GAACCTGnAAGC"AGATCCAA2%ATGCTAATA.AAATCAATCGCGTATC.TT GAAGG AAzATGG TAAAC-ATCTT.ATTACCA.ACAC-TCCCAAAC (-GCCC-AC CAGGTGTT TTTCCTA4AACAG GGGGA ATTG GTACA;'ATTG TCTATATA'TTAG'TTGGTT4CTA %CTTTTATGAPTAC TTACCATTTGTTCTWTI-CClGTCGTiAA CAATTGTAA - R C) MKKQK1, 1GLS VTML.L 7SL ?FG 101LVsC3YQD 2QAL V1 VKTG DNATFLGRA-T FV L KNDN DK S E T RE TVEGSGEATFEN KFGDYTLREETAPI 0Y XTDK T ,-N<rJADNGAT1 IEG MDADKAEKRKEVLNAQY SKSAI YEDTKENYPLV rNVEG-SKVGEQYKALt 21NGKDGRREI',AEG4WLSCKK1TGVNDLf)-DKNKY KI ELTVEGKTTVETIK SLNQPLDVVV,,LLDNSNSMjNNERANNSQRALKAGEAVEELI OKI TZ*4KDNRVAVTYAST1 FDGTEATVSKCV ADQ NGKALNDSVSWDYHKTTFTATTHN2SYLNLTND)ANEVN1iLKSPU PKEAEIIITNGDRTLYQFGATFTQK AL .5 MRM4EI LET QSSNAW .KLI FHVTDGVPTNSYAI-NfNPYI NTYNFSLK PSGLQDI NDD QIVKGDGESFKLFSDRKVPVTGGTTQAAYRVPQNQLSVNS. )EGYAINSGY IYLYWRDYfNWVYPFDPKTKYVS AITEQI KTHGEPTTLS FNGN I EPGYDI FTVGIGVNGDPGA'T PLEAEKFMQS ISSKTENYTVDDTNKI DEL NEYFET IVE ;iSIVDG'VTDPMGEMI EFQLIKNGQS FTHDDYVLVIGND GSQLKNGVAPLGGPNSDGGI LXDVT \TTYD 'TSQTIKICHIALGSGQKVVqLTYDVIRLKDNY ISNEFYNT NNRTTLS FESEKE PNT I RFO I 21(1DVA, 20 EFIVIT ISNQKKMGEV,,F.FI rV'DKHSESLLGAKFQQ11EKDFSGYQFVPEGSDVTTNDGRIYFALQDG I4YKLE I SS PlAIT I EVrKTKPVVTFT I QNGEVTNLKADPNANKNQI GYLEGNGKHILI TNT PKPP GVFPKTG IGT IVY ILVGSTFMI LTICSFRRKQL Strain 1C244 25 GEE DNA sequence (SEQ ID No, 210), ATGCAAAAAGk'AGACAAAAA ATATGGAGAGGT TATCA-TTACTTTAC'-TAAT-CCTGICCCA-AATTCCATTTGG T ATATTGGTACAAuzGGTC-AAACCCAAlGATACCAAT CArAGCATTGGAAAzAGTAzATTG TTAAAAAA%42 CGGGAGAC ACGGTAGA.GGGTTCT GGAGAAGCAAC-CTTTGA.AA ACAThA'LzACCTGGAGACTAZCACATTAJ4GAGAAG.ACA 30 GThCCAATTG(3TTATiA.-AAMACTGATAAACCTGG AAAGTTAAA7,G2TGCAG CATAA-tCGSAGCAiACAAJTAAlTC GAGGGTATGGATGCAGATAAA GCAGAGAAACG'AAAGAAGTTTTGALATCCCAPATATCCAAAAt'TCAG;'CTATT TATGAGGATAC AAA'AGAAAATTACC&ATTAGTTAATGTAGAGGGTTCCAA~zGTTGGTGAAPCAATACAA1lAGCA TTGAPATCCAATAAPATGGAAGAATGGTCGAAGCAAGATTGCTG AG-GTTGGTTATCAAAPLA~lAATTACA'GG GTCA.ATGATCTCG.ATAAGAATAAATATAAAATTGAA T A4ACTGTTGAG.rGGTAAAACCAC'TGTTGAA ACG ,lA 35 GAA %CTTAAT-CAACCACTAGAPTGTCGTTGTGCTATTA'GATA'ATTCA ATAGTATGAA %TAATGAAAGA GCCAAT A4ATTCITCAAAGAzGCATT~AAAGCTGGGG,-AA GCAGTT GAAAA.GCTGATTGATAA?%-ATTACAWCAAATAA; AGAC AAkTAG AG TAGC-TCTTGTGACAPTATGCCTCAACCATT TTTGATGGTACTiAAGCGACCGTA.TCAAA 1GGGAGT GCCGATC7AAATGGTYAAAGCGrCTGAAPTGIATAG TGTATCATGGG ATTATCATi'AAAACTACTTTTA CA GCAlACT A.CACATIA.TTACAGT TATTTAAAtTTTzACAAATGTGCTACGA32AGTTAATAITCT'tAAGTAGAAi.ZTCCA 40 AA GGAA^GCGGAGCATATAAA TGGGGATCGCACGCTCTATCAATTTGGTGCGACATTTACTCAAAAAGi CTCTA ATGA.AGCAAATGAAkATTTTAGAkGACACAA7%AGTTCTAATG;CTAGAAAAAAA.V-CTTA^,TTTTTCACrGTAAJiCTGAT C-GTGTCCCTAC-GATGTCTTAT GCCATA AATTTTAAT CCTTATATATCAACATCTT-ACCA,AACCAG'-TTAT TC'TTTTTT&1<ATAAVurTAPC-'CATA GAAGTGGvTAc'TTCTCCAAG-AGSATTTTATAATCAATGGTGATGATTAT CAAATAGTAAAA.GGAGATGGAGAGAGTTTTAAACTGTTTTTCGGATMAAAAGTCCTGTTACTGA.-GGA C 45 ACACAtAGCA, GCTTATCGAGrTACCGCAAAATCAACTCTCT2TAATGAGrTAATG G GGATATGCAATTAATAGT GGATATATTTATCTCTATTGGAG3AGATTACACTGG5GTCTAzTCCATTTGACCT'AGACAAGAGL%-TWTCT GCAAC%.^GAAACAAzATCAAAACTCATGGTGAG CCCAACAA$CATTATAC-TTTAzATGGAA.TATAAGACCTA IAGGT TATGACSATTTTTACT,--GTTGGG2ATTGGTGTAAACGGA %GATCCTGGTGCAkACTCC.TCTTGALAGCTGAGAATTT ATGCAATCAATATGAGTAAAACAGAAr AATTATAC-TAnTGTTGATGATACAz AATAAA,TTTATGnTGAGCTA 50 AATAk-ATACTTTA. -AACAATTG-TTGAG GAAAAAACATTCTATTGTTGATGGAAATGTG ACTGATCCTATvGGA GAGzATGATTGAATmTCCAATTAAAAATGGTCA-AAGT TTTACACATGATGATTACGTTTTGGTTGGAAsATGApT GGCAG':TCAAPTTS'AAAAATGGT'GTGGCTC'TTGG TGGACC-AJA CAGTGATGGGGGATTTTlaAAAGATGTTACA GTGAQ .T' TGATAAGA ,CATCTCAL %jCCATCAAAAVTCP3C',CATTTGACTTAGC-kkGTGGACAAAAAGT-C-T CTTACCTATGATG.TACGTTTMkA.AGATAAkCTATTAGTAACAAltTTTTACeATACAATAAzTCGTACA'ACG 55 CTAA-GTCCGAAGAiGTG ^Ai AAAAGAAaCGAAtATACTATTCGTG ATTTCCCAATTCCCAAAA TTCGTGATGTTCGT GAGTTTCCGGTACTAACCATCAGTAATCAGAA-GAAAAJTGGGTGAGGTTGA2It',TTATTAAXAGTTAATP,AAAAC .AACATTCAGT.CGCTTTTGGGAGCTAATTTCACTTCG(ATA(AAAAtGTTTTTCTGGTATA GCnAA TTTGTTCCAGAGGGAAGTGATGTTACAZ;ACAAAG AATGATGGTAAzAATTTATTTTnA AGCACTTCAAGATGGT AACTATAA,4ATTATATGAA4ATTTCAAkGTCCAGATGGCTATATAGAPGGTTAAAA ,CGAAT1ACCTGTTGTGACA TTT 60 ACAA: TTCAAAzATGG. GAAGTTACGzAAC-CTGPAAGCAGnTC-CAAA%-TGCTAATAA,AA CAAAnTCGGGTATCTT GAGQATSGTAA ACATCTTATTACCAAC-AC-TCCCM..A.ACGCCCACA-.4GGTG"TTTCCTAAAACAGGGGGA A TTGTACATTGTCTATATATTAGTTG GTTCTAkCTTTTATGATACTTACCATTTGTTC-TTTCCGTCGTAAA.F C AATTGTAAi 2PY amino acid euec (SEQ ID N-3. 191) 5 MKEQ( WR~SVWL LEI ro LVQETDTNALKV IVKKTGDNATPLQKA TFW7LKNIDNDKSETSH-E TVEGSGEATFENX KPGDYTLREETAP1 GYKZTDI TWKVKVADNG3AT 1IEGMDJADKAERRKEVLNAQY ?KSAI. YEDTKENYPLVNV- EGSKVGEQYK'ALN PTNSKDGRRE IAEGWLSKKXTGVN4DLD)KNKYE'I EITVEGETTV/ETK ELNQPLDV'VVLLDNSNSM,,NNERANNSQRALKAGEAVEKL1 DKITSNKDNRVALVTYASTI EDGTEATVSXGV ADQdNGKALNDSVSWDYHRTTFTATTHNYSYLNLTNDANEVNI LESRI SKEASH INGDRTLYQFG ATFTQKAL 10 MKAN EILE--TQSSNeARKYKLIFHIVTDGV1TSYINfllIPYISTSYQNQF-NSFLNKIPDR-SGlLQEDFI INGDDY QIVKGDOESFKLFSDRKVPVTSGTTQAAYPVPQ'PNQLSVMISNEQYA1 NEGY 1YLYWRDYNWVYPFPPKTKKVS ATKQ1-KT)-GEPTTLYFNG'NIRPKGYDIFTVGGVNiSDPGATPLEAEKFM4QSISSKTENYTNVDDTNKIYDEL NKYFET IVEEKSIVDSNVPTDFNGoEN, I FQVLlS4GQSFzHDYVLGrNDGSQLKNGVA, LGGPNSDOG1 LKDVT' VTYDKTSQTIRINXLNtLGSGQKVVLTYDVRLKDNYISNKFYNTNNRTTLSPKSEKEPNTIRDFPIPKIRDVR? 15 EFPVLT I NQEENGE VEFI NKDKWSESLLG-FQLQIEKDFSGYQFPEGSDVTTKNDGKIY-KALQDC~ NYKLYS ISE PLOY IEVKTKPVVrTFTI QNSEVTNLRADPNANKNQIG? LEOGNGERL', I T1TPKRPPGVJFPKT GG, ICY IVY ILVCGSTFMI ET ICSFRRKQL Strain 1C245 2 0 ORF DNA segiuence (SEQ ID NOQ: 211) ATG AAAAAGAGCAAA%AATATGOAAGGTTATCAGTTACTTTAC-ThZATCCTCTCOCAAZATTOCATTTGGT ATATTCGTAC-AAGGTGA AACCC'-AAGATACCAATCAACCACTTGGAAAA2GTA;ATTGTTAAAAAAC.CGGGAGAC AATGOTACACCATTA'CCGCAAA GCG ACTTTTGTCTTAaAAAATGAA-)ATATAAGT-AAA2 ACAGTCrACGvAA ACGOTACAGSGTTCTOGAGAAC CAAC:CTTAAACATAAACCTOQAGACTACACATTAAOCAACA,,AAC A 25 CCACCAATTG-GTTATAAAAAAAC-TGATAAAAO 1CC-AACTTAzAOTTGCAGATAOOGAGCAACAAkTAATC CAGSGTATGCATCCACrATAACAAS-AAAGA-AAGAA lGTTTTGAATGCCJAAiTATCCAAA ATCACCTA'TT TATGAGGATACAA-AACAAAzATTACCCATTAGTTAkATGT.ACAGSGTTCCAMG.7',TTGT'ACATAiCAiAC2A ,TCAA.PTCCAATAAA UTGGrAAAZAGATCSTCGrAAGAGACGATTCTCAACCTTCCTTATCAAA AAA.AlATTACACvGG GTCALATGATCTCS"CATAAGAATA^iAATATAiAATGA ATTAzACTO-TTGAGGO^TtAAAOCA CTGTTA1 AACGAAA 30 (1 GAAOTTAATCA-ACCA CTAG ATGTCGT4TGTG CTAT-TA-ATAATTCAAATACTATCAATAATGAAAGAGCCAATm AA)TTCTCAACACATTAVAGCTCCGAACATTGJAAGTGATTATAAATTACATCA-,TAAASGAC AATAGAGTAGCTCTTGTGAzCATATGCCTCAAZCCATTTTTGATGGTACT A.AGCCCGTAnTO" AAGOCAGTT CCSATCAATOGTAAAOGCSCTGVAATGATAGTOTATCATGGSATTATCATAAAA ,CTACTTTTAACAAO rT ACACATAA,,TTAOCAGTTATTTAAJATTTAACAAATCA TSCTAACOAAGTTAATATTCT- AACTCAAGAATTCCA 3,5 AAC-GGAAOGGAGCATATA-AATGGGGATO-GCACGCTCTATCAATTTGCTCACATTTACTCAAAACC TCTA ATGAAAOGCAAAkTGAAATTTTAGAGACACAAAGTTCTAATGTAGAAA~i-AATTATTTTTCACTACTAT~l GGTGCCCTACGATGTCTTATGCCATAAATTTTA.ATOCTTATATATCAACATCTTACCAAACOAG; TTTAATil TCTTTTTTAAATA?2AATA CCA GATAC-AAGTOGGTATTOTCAACAOGGATTTTATAiATCA.ATGGTGATGATTAT CAz h.tATAAAAC(GAGATGzC-AAGAGlTTTTAA CTGTTTTCGCATACAAAAG-TT COTGTTA-TC-CAO G.AG 40 ACACAACCAGOCTTATCOAGTACOOCZAAATOAACTCTCTGTAATSACTAATrGGCATATGCCAAiTTM' TAGT GCATATATTTATCTCTATTCGGA~GATTAC'AL'CTCGGTCTATCCATTTGATCICTAACACAAASA ASTTTCT GCOOS O; ,LA.AATOAAOkTOATOCTSACOCAAOAAOA ,,zC~TTA'TACTTTAA-TS-GA'AATATzL-AAGACCTAAAS-kGT WATGAOA'TTTTTAkCTGTTGCGATTCGTGTA.2AOGCAGATCCTGGTGCAAC-TCCTCTTGAPGO-TCAGAAkATTT ATCAATOAATATCAAGtCTAAAAOJAGAAAA~uTTATACTAATGTTGA TGATAC-AATAPAAATTTATGATGAGCTA 45 AATPAATACT'TAACAATTGTTGAGGAAA AACArTTCTATTO-TTGATOGGAA-TTOAOTGATOCTAT GGGA GAGATGATTGAATTOOAATTIAPiATGGTCA.AGTTTTAAO1rATGATCATTAO-GTTTTGTTGGAAATGAT GGCAGTCAATTAAPAA.ATGGTGTGCTOTTGGTGGAOOAAACAGTGA'TGGGGGAATTTTAAAAGAiTGTTACA GT(OLO TTA TCAI-TAAAATO TCAAAO-PCATO'-AAA' ATOAATCATTTGAAO-TTAGGAAGTG GAO-A,-AAAAO TACTT OTTAOCTATG ATCTACGTTTMAAGATACTATATAGTAAAATTTTA-AATA-AAA TAATCG'ACAA-G 50 TAAG,,-TOOGCAAG AGTCARAAGAOAAATAO-TATTCGTGATTTCCAATTCC-.AAA,?TTCGTG.ATCr'TG GAOTT TCOGGTAO.TAAOCATCAG2TAATO AGAAO2 7AAATGGGTCGAGGTTCAAT TTAT'AAAGTTAAAAAGAC AAACATTOAG.AATCCTTTTGCAGCTAC -T.TTAATTCA3TAGAAAAC-ATTTTTCTCG,'GTATACCA TTTGTTCCASAGGGA~tCTCATGTTAOAAOAAACAAzTG ATGG 'TAAAATTTATTTT-AAAGCAOTTOAAGOATG AACTATAA ATTATATOAA ATTTCAAC TCAGATGGOTATATAGAGGTTAAAOO'iCAAACCTGTTGTGAOATTT 55 AOAATTCAAA-UATGGAG AACTTACGA-AOCTGAAAGCAGATOCA.AAZTGC'TA.ATAAAAATOAAiATCGGG7TAITCTT " G AA7GGAAA TOOTAAAO~rATCTTATTAOCAACTCCOOAACOCCCAOOAGOTGTTTTOOTAAAACAGGGGA ATTGGTACAATTGCTTATATATTAGTTCSTTCTAOTTTTATGA' TACTTAO-CATTTG ITTTTTCGTCGTAA, CAATTGTAA OAF amino acid sequence (SEQ ID NO: 192).

-115 NKEQKI WRGLSVTLLI LSQI PFG II LVQGETQDTNQALGKV IVKKTG DNATPLGKAPTFVJLKNDNDKSETSHE WVEGSGEATFEN 11<PGDYWL REETA? 1GYKET DXtThKVAADNGAT IIEGMLDA.DKAE KRKZVLNAQY P1SA: YEDTKENYPLVN 9EGSKVGrEQYKALNP 1NG-KDGRPRE IAEGW ,LSKKI TGVNDLDKNKYK1- ELTVEGKTTVETK, EL PIJVVVLDNNSMNEANNQRAKAGAVEL1DK ITSNI DN. ,RVALVTYASTI FDGWS-ATVSKGV 5 ADQNGKALNDSVSWDYRWTFTATENYSYLNLTNDANEVI LXSRI PKEAEHINGDRWLYQFGAWFTQ-A.L MKANIEILETQSSNARKKLIFI-VTDGV'P~TSYAINFNPFY1STSYQNQFNSFLNKIPDRSG1LQEDFI INGDDY QIV KGDGESFKJSFSDRKVPVTGGWWQTAAYRV PQNQLS-VN SNEGYA1 NSGY IYLY RDYNWVY PFDFKTKKVS AWKQIKTHGEPTTLYFNTGNIRPKGYDTFTVGIGVNGDPG- AW PLEAEKFAQSISSKTENYTNVDDTNKI YDEL KYFK.WIVEEKXS IVDGNVTDPMCE4I EFQLKNGQSFTNDDYVLV GNDGSQLKNGVA' LGG PNSDGG ILKDVlT I0 VTYD XTSQT 11< NI NCGKWTDE 3DY NKFYNTNNRTTLS PESEKEPNT1 RDFP I P1<1 R-DVE EFPVLT ISNQKEMGEVEFIKVNKD 1tSESLLGAI{,FQLQIEKD)FSGYKQjFVPEGSDVTTKND)K 1 YFKALQDG NYI LYE I. SSPDGY I. EV'KTKPVVTFW 1QNGEVWNLKADPNANKNQI GYLEGNGKHI TNT F9KRPPGVFPKWTGG 1GW IVY ILVGSTFMI LW 1CSFPRRKQL 15 Strain 1C246 QRF DNA sequence (SEQ ID NO:l 212). ATG.MAkGGCkA~AAGAAGTAF,,ATTC TCATCGCCJkTCATTG A.TATTGGTACAAGWGAAACCCAACATACCAATCAG.'-CACTGGz~AA AGTAATWGWTAAAAAA, ACGGGAGAC AATGCTACACCATTAt.GCAAAGCCACTTTTWTGTTW,AiAATGACAATGA ,TACTCAGA%.eACA',AGTCACGrAA 20 ACGGTAGAGGGTWCTGGAGzAAGCAACCTTTG.AAAACATA-AAA.CCTGGAGAC.-'TAG-ACATTAAG.3.-AAAGAA74ACA GC ACCAATTGGTTATAt; ACTGATA ACCGGA-AAGA3AA GTGCAATAACGGAGCAACAATAWC GCAGG G T AT GGATQG.CA A T AAGCAAGAAAC G AAAG iAGTWTT T GAA TGC CAAvTAT C CAAAA T-CAG CTAWTT TATGAGGATAC- aAG(AAWATACCATG TTAATGTAAGGTTCC7ACTGfTAACAAT CAAAGCA TWG ATcC ATkAT GGAAORATG T CGA AGA GAGAT T-G CWGAGG TTG GT T 7,T C AA!AA*A2 T ACA GGG 25 GW CA-T GAT CTC GA TAAGAAWTAAA A TAAAA T T GAAT A AC TGT T G AGGG TAAAA C CA C T G TG ALAa GPACTWAATCA ACCACTAG7AWGTCGTTGWGCTAWTAGATAATTCAA.AWACTATGAATA IATGAAACACCAAT AWTT CWTCAAAGAGCATWAA'%AAGC T GGGGAAGCAG TT GAAAGC TGATWTGATAAAATWTACAW CAAATAAUAGAC AAT CAGTAGCT .. TTGTGACATATGCCTCMkCCATTTTGAGTACGAAGCGACCGTAWCAAkAGOGAGTT GC-CGATCAIMVATGGTAAz'AGCGCTGAAWz GATAGTGTATCATGGGATTATCAWAAAACTACTTTTACAGCAA CT 3 0 AO-ACAW AATTACAGTTATTTAAATWTAA-AAATGATGCTJA%CGAA %GTWAAWTATTCWAAAGWCAAGAATTCCA YAG7GAAGCGGAGC-ATAWAAAW&GGATCGCACGCTCTATCAA TTTGGWGCGACATTTACTCAAA-A AGCTCWA AWGCA~AGAATAAAWATTTAAGACACA~AGTCTAAT CTAGAA,AAACTTATWTTTTCACGTAACTGAT GGTGTC-CCTACGrATGWTWTATGC-CATAAAW.TTT TAATC'CWTAWATAWCAAZCATCWTACC--AACCAGTTTAA3%T TC-TTTTTTAAATAAAATACCAGATAGAGTGGTW'T-TCCAAGAGGTTTATAi4TCAATGGTAWCATWAT 15 CAA AWTAAAIAG GA GA TCGGAG AGAC TT TT-AAACWG TTTWTC GGA TAG^AAACTTWCCT G TTAQCTCA GC0AA CG ACCAGCACGCTWATCGA -TAC(2GCAAAATC. ACT-CTCW-GTAATGAGTA ATGA'GCA71TA2TCAATTAA TAG T GG;ATAW-ATTTA TCWCTATWGGAGAGATTACACTGGGOTATCCATTTGATCTAGACA,ACAAACz',TTTCT GC'-AACGAAA.CAA,&ATCAAADACTCATGGTGAGCCAACAACA.TTAACTTTAAiTGGtAAWATAAGACCTAAAiGGT TATGAilCATTTA~'CTGTTG GGAWTCGT-GTAAACGGAGAWCCWGGTGCAACWCCWCTTGAAGGTGAG,AAWTT 40 AWGC.ATCAATAWCAAGTAA.. bQAGAAAA~jT'TATACTtiAWGT TGATGAlTACPAAWAATTTATCAWTGAGCTA AATAAATACTTTAIAAACAATWGTTGAGGAAAAZACATTCTATTGTTGiATGGAAAWTGTGACTGATCCTATGGG7A GAGAt'TGATTGAATWCCAATT AAAAAAT ,GGTCaAA2GTTTTA-CACATGAWGAWWACGTTTTGGTTGGAAATGAT GG-CnGTCAATTAAAtAATGGTGTGGCTCTTGGCTGGACCAAACAGTGAGGGGGAATWTTAAA GATGTAPCA GTGAPCTTAWCATAAG?'ACACCA;ACCATCA.AAWCAA± CAWTTGACW £-- AGGAA43-TGGACA.2-AAGnTAGTT 45 CWTACCTAWGATGTACGTTWMACAATACTATATAGTAA AAWTTTACAAWACAAAPTA4ATCGTACAAPCG CW;AACWCCC'AAGAGTGAc.-AACACCAZAnTACTIATTCGTG TTTCCCAA-T-CCAAiAATTCGTCAWGTTC-GT GAG7TTWCC-GGT ACTAACCATCAGTAA"TCAGAAGAAAA T GGTGAGCTWGAAWTTTATTAAkAGTTAAPT.AAGAC AACATTCAPGAAWCGCTTWWGGAGCAA'AGITTTCACWWG-'- AGATAGA.,AGWTTTTCTGGGTA ACCAAI TTC-TTCCAGiAGGAALGTGAWTGTTA CAAC AAGAATGAW 'GGWA, ATATTAWTTWAAA GCACTTCAAGATGGT 50 A ACTATAAATTAWATGCAAW.TTCAACiTCCAGCATGGCTAW-ATAGAGGTT AajJCaCG?:JCCTGTTGTGACATJTT ACA";ATWCAXAATCVGACAAGTAGAC A3 G---PATCAZT-tA~AC~)ACGTTT GAAGGcAAA TGGTAA, L 5 QATCTWAtTTACCA ACA CWCCCAAA'CGCCCACCAGGTGTTTTTCCTAAlC-AGGGGGA% AT TGCTAC AATTCTCTATATAT TACT'TGGTTCT-ACTT TG1,ATAkC TTWACCAT WTO WICT TCCGTCGTAAA CAATWGTAA 55 Or amino acid sequence (SEQ ID NO,: 13 MKKRQKIN)RGLSVTLL ILSQ I PFO 1 LVQGETQD)TNOnLOKVTVKKTODA WTLOKATF VLKNDNDKSETS-E TVEGSGEAT FEN IKP ,DYT LREETAPGYKKW DKTWKKVADNGATI I EGMDADKAEKRKEVLANAQYPRsA1 YEDT1<SNYPI'LVWJEOSKVGEQYKALNP1 NGKDORAE IAEONLSKKNTG-VNDLDKNKYKI ELTVEO1<TTVIEWK ELNQPLD ,VvLLDNS14SN11NPcEr<AN,:NSQRALKGA-nVEKLl 11<1TSNKDNR-VALVTYAST IFDOWTEA-TVSKGV 60 ADQNGI<ALNDSVSWDYNKTTFTATHNYSYDNLTNOAN!,EVN I LSRX PREAEHINODRTLYQFGATFTQOKAL MKANE I LETQSSNAPRKKLI- FHVTDGV2TM4SYAIN4FNP:Y 1STSYQNQFNSFZN,,KI 2DRSGI LQEDFI I NGDDY Q IVI GDGESFKLFSDRKVJPVTGGTTQAYRVF, IQNQLSVMSNEGYAINSGY 1 YLYWRDYNWVYPFDP WKKV,,S ATKQIKTHGEPTTLYFNGNIRPKGYDI FTVGIG'VNOJDPGATPLEAEKFMQSTSSKTENYTNVDDTNKIYDEL NI{YFKT IVEEKHS IVDGtrVTDPNGEMI EFQLKNGQ^-SFTH-DDrTVNDG-SQLINGVA71LGGPNISDGGI LKDVT, .5 VTYDKTSQTIKINHLNLGSGQKVVLTY VRL KDNYIS4KF'YNTNNRTTLSFKSEKEPNTlPDFPTPKIRVP. F E FPVLTJT SNQEKMGEVEFI- KVNKDKHSESLLGAKFQLQI- EKDFSGY7QFViFEGSDVTTKNDGKIYFKALQDG NYKLYETI S S PDY I EVKTKPVVTFTI QNOEVTN LEADPNANENQIGYLEGNGKHIJIT TNT PKRPPGVFPKTGG .IGTIVY:ILVGSTFMN1 LTICSF'RP{QLJ 10 Strain 1C247 ORF DNA sequence .. (SEQID NO: 213) ATPJ~.AGGCAAAATTGAAGGTACA GTTACTTTACTtACTCTCCOAAA-UTT,,CAPTTTGGT ATATTGGTACAAGGTGAA.ACCCAkAGATACOAkATOA2AGCAO-TTGGAAAkAGTA ATTGTT~kA.AA.AACGGGAGAC AATC-CTACACCATTAGGCA2kArGOACTTTTGTGTT AAAATGACAATGATA,4GTCAGAAACAkAGTCAOGAA;' 15 AOGOTAGAOGGTTCTGO7AOAAGO,,-AOCTTTOAAZAACATAAAACOTGGAGAOCTACAOATTAAGAG'AAGAAA GCACCAATTGGTTAT AAAAAAACTGATAAAACCTGGAAA.GT ' AAGTTGCAGATAOGGzAGCAACAATAz ATC GAGCGTATGGATGCAGCATAAAG-CAGiAGAAACkrGAAAPAGAAGTTTTGAATGCCCIAATATCCAAAATCAGCTATT TATGAGCr;N"ArCAAAAkG 1 A~AATTA.'CCATTAtG7XTAkIAnAGGGTTcOAAAG T7.GGTGAACAACAAA2%GcA T TGAATCCAPATAAATGGAAAAGGTC GAAGAG~AGATTGCT-GAAGGT TGGTTATOA-AAAAAAt TTACAQGGG 20 C-TCA ATGATCTCOATAACGAATAAATATYAAA TTGAA.TTAACTOTTGAOGGTAAAAhz CCACTGTTGAA ACGAAAk G3AAOTTAATCAAfCl CTAGATGTC GTTOTOOTATTAGATAATTC'AA-TAGTATGA.ATAA T AAAOAG CCAA'T AATTCTCPiAAGAGQ-ATTASXl-AAGCTGQGGrCAC-TTGAAAAGCTGATTOATAAYAATTACATCAAZT 5 AAG AC AATAGA GTAOCCTCTTGTOACATATOQCTCAAC,,rCATTTTTGTGGPACTOAAGCGACCGTATC AAGGGAO TT GCC-GATOA.1AATGGTA.AGCG GATGATAG TGTATC-ATGGGA TTATOATAAPAACTACTTTTACAGCAACT 25 ACACATAATTACAGTTATTTAtAATTTAAOAA-rATGYATGGTAACG3AAGTTAiTAkTTOTMiAAGTCAAG(AATTCCA AAGGAAGCGSAGOATATAAATGGGGATCGCACGTCThTCAATTTGGTGCGACATTTAOTC-AA.DAM GCTCTA ATGAAAGC'-AA4TGAA ATTTTAGA.GAC-ACAAA GTTCTAAkTGCTAGAAAAAA;ACTTATTTTTC-ACGTAACTGAT GTGTCCCTACG A IGTTTATGCCATAAATTTTAATCCTTA TATA TCAA ICATCTTACCAAAACCAGTTTAAPT TOCTTTTTT AATAA.AJ\ATACC-AGAT,. AATGGTATT -CTCCA.AGAGGATTTTA-JAATCALATGGTGATGATT±IT 310 O-AATACAAG AGAATGAGAGAG,-TTTTAACTTTTTG-ATAAAZJAGTTCCTG-TACTGAGAACG ACACAAGO-AGCTTATCGAGTACICGC A,4AATCAACITCTCTGTAATGAOzTAATGAOQGGATATGCAATTAATAOT GOAkTATATTTA TCTCTATTGG-AGAGATTACAACTGGGT4CTATCCATTT ATCCTAG.'ACAA.GAAGrTATT GGAAOCG tA ^V1T-CzCTCTG^-GTGGACCA~CATTATATTTA'3TGGAAATATAGACCTAIAGGT TATGAO.ATTTTT-ACTGTTGGOATTGQTGTAALACGGAGiATCCTGGTGCAA.CTCCTCTTGAA.GCTGAGA4 ATT 35 A TGCAA-TOAATATCIAAGTAA-iCAGAAAkiTTATCTSATGTT ATGATACAAALtTAAAsATTTATGA TGA302A AATAADATACTTTAAA ACAATTGTT AGGAAAAACATTCTATTGTTQATGGAAkATGTGrACTGATCCTAkTOGGA GAGATGATTGAATT CCA± 1 ATTAA.2"AATGGT C..AAG T-TTAzCACATGATGA1TTAGCGTTTTGGTTGGAAAUTGAT GGCAGCTOAAJTTAA zi.WATGGTGTGGQTCTTGGTGCOAACt'?ACAGTGATGGGGOJ TTTTAAAA GATGTTACA GTGACTTATGATAAGA.CATCTCrAAACCATC-AAAtATCAAkTCAT'TGA.ACTTAGG-.ACGT(A.CAA,,AAG3TAGTT 410 CTTACCTATGATCTACGTTTXPAAAG ,1ATAACTATATAAGTAACAAATTTTACA1ATAC-AA3ATAA TCQTAC-AACG CTAAGvTCCGiA.PAAGTGAA.AG', AACAAkATACTATW-CG5TGATTTCCCPJ TTCCCAAAATTCGTG ATGTTCGI GAGTT TCCGGTACTA ACCATCAGTAATCAkGAAGA.AAATGGGTGzAGGTTGAAT £'TAT IAAkAGTTAATAAGAO AAAkCATTCAG'AATOGCTTTTGG'GA-OCTA.AGTTTCAACTTCAGATAG7AAAA; AGATTTTTCTOGGTATAAOCAA TTTGTTCCAGA GGOOAAGTGATGTTACAAJCAMOAAATGATGGT AAATTTATTTTt'J\AOCAOTTCAAGATGGT 45 AACTATAAATTATATOAAA TTTCAAGTCCAOATGGCTATATAGAGGTTAAAAZCGAAACCTGTTGTGAQrATTI .AATTLCAA~TGGGVGA Tg'CACCG AGCAATCCAATGCTAiATAAS)JATCAATCGGCGTATCTIX GAAGCGAA,-ATSGrTAAACATOCITTATTAC-zCAACTCOCA~ACGC-CACC-A'GTGTTITCCT.AAAOA.GGGDA. ATTGGTACA ATTGTCTATATA TTADTTGGQTTCTACTTTTATGATACTTAZCCATTTGTTCTTTCOTCGTAAA CATIATTO;TAA 50 oRr amino ac-id saciuonc. (SEQ 1Dl NO: 194). MKFKRQKIWRGLSVTLLI XLSQI PFGI LVQcBTQDTt4QALG' -KV1VKKTODNA.TPLGKATFVL<NDNDRSETSHE TVEGSGEATFENIKPGDYTLREETAPIGYKKTDKTNFI'VADNGATTI EG .DADEAEKRKEVLNAQYPKSAI YE1YIENYPLVN7tVEGSKVGCEQY KALNPI NGKDGRRE IAEGWLSKKITGVNrDLDKNEYKI ELTVEGKTTVETK 55 ADQNGKAI.NDSVSWDYXKTTFTATTHNYSYLNLTNDANEVNI1LKSRI PKEAEH INGDRTLYQEGATFTQKAkL NK-ANE ILETOSSNnRKXLT FHVTDG5VPTMSYAINFNPY1 STSY QNQF-NSFLNK1 PDRSGI EQEDE I NGDDY QIVKGDGESERKsESDRK VPV TGGTTQAAYRVF21QQLS-,V;tSEGYnINSGYI1YET 4RDYNWVYPFDPKTKRFV~S AiTKQIRTHGEPTTLYFNtGN1-RPKGYDIFTTGIGNGDPGATIPLEAEKF'QSISSWENYTNV'DDTNKIYDEL ITEYFET IVEEKIIS IVDCINVTDPM;GEIEFQLKNGrQSFTHDDYVLVIGNDGSQLKNG VALGG PNSDGG1 LKDVT 60 VTYDKTSQTIKINHLNLGSGQRW-LTYDVRLRDNYISNKFYNTNNRTTLSPKSEKEPNTIRDEPIPKIRDr) P -i 17 EFPVLT I NQMGVIKVKESiSLAFQZEKDFSGYKQ2-FVESV TTKNDGKTe,'YFKZALC-DG N;YKLYE ISS2DCY I EVKT K PWTFTI QNGEVTNLA DPNNKNQGYLENGcIiLI TtTPKRFGVBPKTG4 ICTIVY1LVGSTFMILTICSFRRKQL 5 Strain 1C250 (ORE' DA zsgue-nce SEQ ID NO; 214) ATCAkGAtAAATACCAkAATTTTCTAAAP-TATTGA.CGTTAACTCT'TTTTGTTTGTCI CAA.,TACCGCT'TAAT AC CAATGTTTTAGGGAAAGTACCGTACCGCAAAATGCTGCTAAA GG. Ae jGTGTTGTTPiJ 5 ;CAAGA!CAt;AT G-ACCAGAACAAiACCAiCT 'TCAAKiAGCTACCTTTCYTTTTAAAK~liACTAiCTGCTCkAiCCAGAAACrTAAATAC6AA 10 AAAGTAAGTGC-TGAGCTAACAGCTGAACCTAC-TTTTGATAATCTCATACCTGGAGATTATALCTTTATCA GPA G AAIACGCGCCCGlCAGTPTA.AA45('AAGATAACCAkGAC'-TTGGC.ACATTAGTrGAAGTAT-GAAA"AACI ACGATACAA,AAGTCGTGAT-AAAAA.TTCCACAATTGG ACAAAAT CACGAACAACT AGATAA'GC'AGTATCCC CCCAC AGGAATTTATGAAGATACAAA7GGAATCTTATP,AATTGACCATGTTAAAG CGTTCAGTTCCAAAi TGGA PAkGTCACA.JGCAA-kAG3CAGT TAACCCATATTCAAGTGAA GGTGAGCATATAAGAGAAnTTCCAAGGGAACA 15 TTATCTAAACGTATTTC-AGA.AGTAGGTCATTTAGCTCATAATAAATATAA;AATTGAGTTAACTQTCACTGGA LAAACCATAGTAAAACC-AGTtJGACAAkCAZAACCGTTAG7ATGITTGTCTT-CG3TA(CCATAA,-TTC.TAA.CTCA ATGAkATAA%-CGATC(JCCC AA-TTTTC- AACGCATAATAAAGCCAAGAAkAGCTGCCAJ2XGCTCTTGCGACCCA CTAAAGA- TATTTITAQG AGCJ'.ACAGTGATAA-TAGCGTTG CATTAGTT-ACTATGTTCAGoATATTTTTCAT G TA GGA GTG TAGATCGT7C G TVAA GAT T TAAGAA GA TATAAAT AT TATG C C TCAAA CTAAG TT C ACA 20 AT CAGACACACAAT TATAGTCATAAA2 CA ATTAACAAATAAT GC-T'GCCATTATAAAA-zAGGATTCCGAPCA GAA GC T CCTANIAG C TAAG TG GQGGAZTC-TAz C TAC CAA TGGCA TTA.A C;T CCAACA AC AAAAGGA GTAC T A TC TT AGTAAC3TAGGAGAAACATTTACTATGAAA2%GCCTTCATGCAC.GCA(3ATGATATTTTGAGTCAAGTkATCCGA AAt"TACtTCAAAAA2ATTA' TTGTT .ATGTAACTGATGT'GTTCICTACCAGATCATATG-CTATTATAA,1TTTT? A4 CTGGCTGCALTCATATGGCTTTTAACA-T-UIAAAVT'GTATACTAAT LAAACTAA',VT~TTCTA% ACACAGATAATCTCTCAAACTTACAAAALACTTCATTA;TTTAGATTTAAA TCTTA'ATTACCCTAAAG3GT CIA TTTTATCGAAATCGACkCAG A %AGAGALACATGGAACACCAACCAAA.CTTTATATAA.ATAGTTTAAAACAGAAA. AATTATGACA TCTTTAATTTTG-GTATAGAT7ATATTCGTTTTAGACAAGTTTATATGAGATTATAGAAP ThATCAkAGATGCTACTTTTCAAAAA-TTGAAkAGAGCAACCTTTTGAACTTTCAGATGGGGAAATA~kACGAACTA 30 ATGA' AGTCATTCTC-TTCTAAACLCTGACTATTATAC-CCCGATAGzTAAC(-TTCATCCGATGCATCTAACAA TCAA ATTTTATCTAA' AATTCACCAAC. AATTTGA,AAGATTTTAACAAA.AGAA-?AACTCAAiTTGTTAATGGA.,CTATA GAAGATCCTATCGGTGnCAAATC.AATTTACnCCTTCGCr.PtCGACAAACATTGCAACCA AGTGATT-ATACT TATACAGGG 1AATGATGGA AGTATAA7 TGAATAGATAGCATTGCAACTQCTGGGVCCTAA ITAATGATCCTGCAATA C T T AAAGG GG T TIA TTA GAAT A CA TCAAA-VzkT PA A TPCT AC GT TAGAC G TT TGAA 0T TAG G GA GCA CA P I 35 AAAsGTAACACTCACATAT GATCTG.AAACTAGiATCA.CAGTTTTATA.ACTAACAATTCTATGACAkCTAATCGT5 AGPQACAACATTGAATCCT A.AATCAGA GG ATCCTAA cTACA'CTTAGAGA'iT'TT'ICCTCCCTAAAATTCGTGAT GTGAGAG2TATATCCTACAATA',ACG;ATTAAAAP.CG AA"AAAGTTAGG(TGAAi.ATTGAA.PTTTAC 'AAATT3A.T AAAGATAATAATAACTTGCTTCTCAAAGCACCTACGTTTGAAC-TTCAAGAzATTTAAC"TGAAGATTATAACT TATTTACCAPATAAA-AATAA-TAATTCA2-AAGTAGTC ACGCAGA.AAAC-GCCAAAA%-TTTCTTACAAAGATTTG 40 AAAGATGGCAAATATCACTTAnTAGAC.CAGTTTCGIICCACGATTATCAAAAAATTACTA.ATMA..,CCAA.TT TTA; ACTTTTGAAGTTGTT'AAA~zGGATCGATACAMATATAATAGCTGTTA.A T~APCAGATTT CTGAATATC-AT GAGCAACGTG ACAAGCATTTAATTACCAA CACCCATATTCCAC'-CAAAlAGGz'ATTATTCCG ATGACACG'TGGG AAAGGCAATTCTATCTTTCATTTTAAlTA GTGGATCTATGA2ITGTCTAT TGCn(-GTGGA.ATTTATATTTGGAAA. AGATATAAGAAATC-TAGT GATATATCTACAGA AAAAGATTAA 45 OaR avnino acid ateZnce (SEQ ID NO '195) '. NEN, YQKESKI LTLSLFCLSQ IPLNTN' VLGESTVPENGAKG KLVVF KKT DDQNKPLSKA TNVLRTTAQ'PESKIE YVTAEfLTGEATFDNL IPGDY LSEETAPEGYI(K NQTWVVESNGKTT IQNSCIJKNST IGQINQ ELDKQYP KT1VKPVDKQKPLD -,fr:LDNSNSMNNDGPNFQRrnHKAAJEALIGTiYVKDI LG--ANSDN IR-VALVTYGS DIED 50 GR.S'VWRKGEXEDDKYYGLQTKFTI QTENYS}{KQLTNN-AEE 11 ERlPTEAPKI"Zy GSTTNGLTPEQQKEYYL SKVGETFTMKAFMEADDI LSQVJNRNSQRI IVHVTDGVPTRSYAINNFKLGASYESQFEQ KR EYLNKSNFL LITDKPEDI KSNCESYFL-IFPLDSYQTQII 1 SGNLQKLHY LD1;N LNYPKG;TEYRN4GPVREKHGTPTKL Y IS LEQE N:YDI ENFGI DI SFRQWN ED-,YK rN4QDGTFQKL KEEAFELSDGE It-.TELNK/SFSSKPFEYYTFPIVTSSDASNNE ILSKIQQQFEKILTKENSIVJNGTIEDPMeGDKINLQLGNGQTLQPSDYTLQGNDGSIN KDSIATGGPNNDGGI 55 L KGV.KLEYI KNKLYVRGLNL GEGQKVITLTYDVKLDDSFI SNKFYDTNGRTTLNPKSEDPNTL RDFP IPK? - RD 'VREYPTITlKNE: KLGEIEFTKVJDKDNNKLLLKGATFELQEFNS9DYKLYILFIKNNN SKVV7TGSNGKISYKDL KDG KYQL IEAVEPEDYQEI TIJEPI LTFEVV' KGS IQ4I IAVN'KQI SEYJ{EEGDKNLI TNTR I PPEGI IPMTGG KGILSFIL1GGSMMSIAGGI.YIW .RYKESSD!-SREKD 60 [LStrain IC2Si61,__________________ QRF__DNAsequence (SEQ ID NO: 2151 ATGAiAAAGAGACAAAAA,.TATQG(,AGAGGTTATC AGT TAG I STAG TAATCGGTTGGGGAAA,"iT IGGATS TOOT' ATATTGGTAC'AAGGTGPLAACGAAGATACGAATGAAGGCACTTGGAAA.AGTAATTGTT'AAAAPAAGGGGAGAG, AATGGTAGAGGA'.TTA GGGM.AGGAGTTTTGTGTTAAAA ,ATGAGAATGATX GTGj AA;AAAGGAGGAAt S ACGGTAGcAGGGTTG GGAGAAGCAC-TTTG.;AAAATA-AAGGTGGAGAGTAGAGATTAAGAGMAAGAC GCA^CAATTGGTTATAALkA. AATGATPAAAGTGGAAAGTTAA.AGTTGCAPGATAAGGGAG CAAATAATC GAGGGTATGGATGG.AGATAAAGGAGAGAAACGAA;6AAGAAGTrTTGAA-TGCGGCATATCGAA ,AATCAGGTATT TATGAGGA TACGAAAAGAAAATTACGATTAGzTTAATGTAGAGGGT TCCAAAGTTGGGzAACAADTAGAAAkPGCA

T

m G AATGGAAPTA,%ATGG PAAAGATGGTCGGAAGAGAGATTGCTGAG CGTTGGTTATCAPAAAAA-A6ATTAGAGG 10 GGAAGGGAAAATTAATATACTGTT GAGGGTAIAGAGTGTTGAAGtG A G AAGTTAATGAAGGAG-TAGATGTGGTTGTGCTATTA-AzTAATTGAAP ATAGTATGAATAATGAAAGAGGCCAAT1 AA TTCTCAAAOGGATTAAAA GCTGG-GGAGAGTTGAPA GC TGAT TGATiAA 'TTAATCA,TA, 'AAG A ATAGAGT-AGG-TCTTGTGACATATGCGGTCAPACCATTTTGATGGTATGAAG4SAGCGTATGAA.GGGA GTT GOCGATGAlLAT GGTA AAGCGGCTGAAkTGATAGT GTATGCATGGGAT TAT CATAPJIkAClTAC T TTTAGAGCXACC .5 AAAAATGGTATAATTAAAGTGCTAAGGAAGTTAATATTCTAAzGTGAAGA'ATTCGA, A AGGPAGCGGAGCATATAATGGGGATGGCACGCTGTATGCAATTTGGTGGGACATTTAGTCAA, AAGGTCTA ATGAAAGCASATGAATT TTAGAGACACMAGTTC TAATGTAGAAAAAGT TAT T T T TCAGTAAGTGAT GGTGTGGGCTAGGATGTG-TTATGGCATAA21ATTTTAPATGGTTATATATGAAGP.ATGTTAG.AA1ACGAPGTT TAAT TCTTTTTATMTGAAAGATGATTCAATTTTTTATAATGAATGGTGATGAT TA 20 GAAttTAGTAAkAAG3AGATGGA(3nGAGTTTTnAAG,.TGT-TTTGGGATAGAAAG -TTGOTGTTAGTGGAGGAACG

AACAAGCAGCTTA

4 . GGAGTACGCGAA.ATGAAGTGTCTGTAATGAG TAATGAGGGATATGCAATT;AAT GGATATATTTATGTCTATrG,AAGATTACAGTGGGTT TCGATTTGT'C4A AGAGAAA; GAAAGCThTCT GGAACGAzAACAA-ATGADAAA CTGATGGTGAGCAAEAGATTA.TACTTT-AATGGA.-ATATAAGAGG'TAA? %'GT TATG AC'ATTT4TTAG-TGTTGGG-ATTGGTGTAAGCGGAGA TCGTGG TGGAATGG'TCTTGAAGGTGAGAA;ATT4 25 AT GGAATG~-TATCPAATPGrAAAAV1ATTATACTATGTTGATG..ATAGAIT;A iTTATGATGA& £5TP ATATAGT~hGAATGTGAGAAAA~ TTATTTGTATGGAATGTCCTtGTATGTA TGGGA5 r GAGA OTTGAA ,TTCCAATTPAAAA,'ATGGTCAAPAGTTTT ACACATGVATGATTACGTTTTGGTOGAAA.PTGAT GGG-AGTGAATTAMAAAUTGGTGTGGCTCTTGGTGGAGAAAGiAGTGATGGGGGAATTTT AAAGAZTGTTAGA. GA3-ACTTATGATAA74GACATCTGAAAGGAC.TGAAA-;ATGAA4TCATTTAAGTTA GAAGTGGAAAAAAGTAGTT 30 CTACAGTTGTTi tiGTATTTAvTA ATTAAACil.TvTTPt-G GTAA; GTCCGAAGAGT-GA.AAAGRAACAA7lATAGTATTGTGATTTC"CA'- TGGAAAATTCGTGATGTTGGT GAG4TTTGGGGTAGTAACCATGAGTAATCAGAAGAAkAATGGGTGAGGTTGAATTTATTAAPAGTTAATAAAGAG AAAG.ATTCAGAAT"GGOTTTTGGGAGCTAAGTTTCAkACTTCtQATAGAAAAG'ATTTTTCTGGGTATAAGCAA TTTGTTG 3TGAGGGAAGTGATGTTAG-AACAPAAGAATGATGGTAAAMTTATTTT-AA GCAG-TTCAAGATGGT 35 ;%AGTA-;TAAATTAT-ATGAAA TT TGAAGTCGAGATGGCTA-iTATAGAGGTTA AAL J\CTGTTGTGAC-ATTT AG(-AATTCAAATGAAGT-AGAGTGAAGAGA-.GGAATGCTAdATA.A4ATAATGGGTkTGTT GAAGGAAATGG TAA.AG ATCTTATTACCAACTCGGAM4,".GGGG-AGGAGGTGTTTTTCGTAA71AACAOGGGGGA ATTGGTAGAAiTTGTGTATATATTAGTTGGTTGTAGTTTTATGATAGT J2GGACATTTGTTGTTTCG(TCGTAAA CAATTGTAA 40 QRF a-mo acds~una(SEQ ID NO, 1 6) . TVEGSGEATFENI KPGDYTLREETAPI GYKKTOKThKVKV',ADNGA T ITEGMDAOKAEKRNEVL;NAQYPKSAI YEDTKENTh72VN',VEGSKVGEQYKALN2INGKDOCRRE1AIPEGWISKi-KTGVN-,DLDKNKYKI ELTVEGKTTVETK ELNQFLD'A'VrLLDNSNSNNNER.ANNt~SQ-RALKAGEAV',ERI D1-l TSNiKDRVATLVTYAST1 FDG;TE'ATVS KGV 45 ALDQNGKALNDSVSWDYHIKTTFTATTHINY.-SYLNLTNDANiEVN 1LKSRI PXEAEHT1 NGDRTLYQFVGATFTQRAL MKANE ILETQSSNARKKLIFHVTDGVF',-TMSYAINFNPY 1 STSYQNQNSFLNKI PDRSGI LQEDFI INGDDY QIVKGDGESFKLFSDRKVPVTGGTTQAAYRViPQNQLSVMSNEGYAI NSGYI1YLY WRDYN QY PFDP KTK N ,AT KQIKTHGEPTTLYFINNRPKCYD1FTVrGGVNGDPGATPLEAEKFMQS1SSKTENYTItUDDTNKIYDEL NKYFET IVEEhHS IVDGNVrTDPMIGEN1 E-FQLKN,-GQS FTHiDDYVLVeGNDGSQLXNG-VALGGPNSDGG ;I LKDVNT 50 VT-YDKTSQTIKINHITLNLGSGQKVLTYDL'KDNYISNEFYNTNNRTTLSE'KSEi{EPNTIRDF7PIFKIRDVI(p EFPVLT ISEQE MGEVEFI JKNiSLGKQLlEDSYQVESDTRDRYKLD NYi{LYE I 5520(35EVRTKPVV-,TFT IQNGEVTNLKAz DNANKNQI GYLEGNGKHLI-TNTKRSPGVFPKTGG IGTIVYILTVGSTFTILTIGSFRRKQL ---- ------------------------------- -- 55 Strain E0253 025 ~~seq'nce (SEQ ID NO: 2161) ?A C? GAAAAT AC-AAAATTTTGTA7AAATATTGAGGTT-AAGTGTTTTTTGTTTGTG -AAATACOGTTkTT AC QATGTTTTAGGGGAAA'GTAGGGTA CCGGAAAAT'GGTGGTAAA GAAAO - TTAGTT(TTAAA.FAGACAGT G ACGAG52AGAAACC-tAGTTTGAAAA G0TACCTTTGTTTTAAAAkUCTACTGTCATGAAi~AAGT-AsATAG5 p-, 60 AP, GTA.ACTGCT(3AGCTAA CAGGTGAAGC-TAGWTTTT(3ATAATGTCATAGGTrGGATTATACTTTATCG;P k GAAkACAGCGC CC GAAGGTT ATAAAAAGAC TAACCAGACT TGCCAAGT TAAGTAATATG AT A'(CGAT A CAAA-AT-AGTGG-TG A TAAAATTCCACAAT TGGACAAAATCACGAAGAAC T AATAAGC'AGTATCG CCCACAGGAATTT AT GP.AGATACAAA . GGAATCrT-TTAMCTTGAGCAT TAAGTTCATTCTCAAAT3GAP VtCGTRA0,AGGC 1AA.AAQCAGTTAACCCATA'TTCAAG TG7,-4,CGTGAGCATATAAGAGvAAATTCCAGAGGGAACA 5 TIATOT r zCO;T TTCAGAACTACGGTCAiTTTAGCTCATAATAAATATAAAA-TTGAC ATTAACTOTCACTGGA ITAACATGTAAACCAGTGGACAPACA AAGCCGTITAGATGTTGTCTTCC;TACTCGATAATTCTAACTCA A GCAATAAiCGATGG(-CCAAATTTTC2AAGCATAkATAA7 AGCCAAAAGCTGCCGAA' GCTCTTCGCACCGCA GTAA.,AGATATTTTAGCAGCAAACTGATAA TAG-GGTT-CATTAG TTAC-CTATGGTTCAGATATTTTGAT G CT.,GAGGTGTAATGTCTA.-AAJ400ATTTAAGAA-GATTAAATATTATG-GCCTTC-AACTAAGTTCACA tO ATTCAGACAGAG2AATTATA.GTCATAACAATTAA;6CAA.TAATGC-TCAfAGAr TTA TAAPAAGGATTCCTACA IGAzAGCTCCTAGACGCTAATOGGCGATCAACITACAAA,'CGGACTTAC-TC^CAGAGCAA.CA-AAAGCAGTACTATCTT AO-TAAAGT- AGGG3GAA4CATTTACTATGAAA ,GCCTTCATGGAGGCAAGATATTT'TGA'GTCAACGTAGATCGA AATAGTCAIAAAAATTAT TGTTCATATAACTGATGOTOTTCCAACAA GATCATATGC TA'T TAATAAkTTI-TTAA. TTGGGTGCATCATATGAAAGCCAATTTGAACAAATGA ;AAAAAATC GATATCTA.AATAa-AAAGTAAJ'ITTTCTA 15 CTTIACTGATAA(CCCG;AGGATA.TA-AAAO:GAAA4-TGGGAG;rAGTTACTTIITTTTTCCCTTAGATAGT'TATCAA ACAC-AOATAATCTCTrGCAAACTTACAAAAACt 'TCATTATTTAG( ATTTAA, ATCTTM.iTTACC" .TA-AACGTACA ATTTATC{ZAAPATCOAICCAGT' AA' GAGAACAT-GAACACCAACCAA~i4CfTTTATATAAATAGTTAAGAAA AATTATGACATCTTTAATTTTOGTA TAGATAiTATCTGCTTTTAGA.CAAGTTTA TAATGAGGATTATAUAAAA AeTCAGATG TACT TT TCAA-AA'T T GAAACA!GGI4AOCT T T TAAC T TTCAGzAT GGGGAAATAACAGAACrTA 20 ATGATCATTCTCTCAACCTGAGTTTATACCCCATGTAACTTATCCGATGCATTAACATGA AT'TTATCTAAAATTCACCAACAATTTGAAA.AGGTTTTAACAAt-AAGAkAAACTCAA, TTG'TTAATCGAACTATA GA AGATCCTATGGT GAC?2-FAT CAAT T TCAGC T TGCAACGAC AAACAT TO3CAA-C AAG TGAT TAT AC T TTACAGGAAATGAS'GG-GTATA TAACATAG7CATTGCA,"ACTC-CTGCGCCTAA TAATGCATGGTGGAIATA CTTAAPAGGGGTTPAATTAGAA TACATAAAATAAAC-TCTACGTTAGAGGTTTAACTTAG(GA^jGCCACAAP 25 AAAGTAACACTCACATATG7ATGTGIAACTAGATGACAGT4TTTATAAGTAkACAAATTCTATGACACTAATGGT AGAACAACATTGAZATC-CTA-AAT CAGAOGATCCTAA %TACACTTAGAGATTTTCCAATCCICTAAAATTCGTGAT G TC-AA GAATATC CTACAA TAACGAT TA.AAAACCGAGAXGACGT TAGGTCAAAT TGA.AT TTACAA~AAGTT X-.k AAIPGATAATkT'ATTC rTTCT ;AAAGAiGCTCGTTTGAATTCAGAATTTAATGAAGATTATAAAT TATTTACCAATA.TA~ ATATAATTCAA-TAGTA;TG31CG-GGAGAAAACGOCA.AATT CTTACAAAGATTTG 30 kAAATCOCA-AATATXCAGTTAATAGAAOCAGTTTCGCCG AAGGATITATCA-;AAAATTACTAATAAACC.ATT TTYCTTTTGAG TTTAA"-GGATCGATACAMA~VTPTAATACTGTTA.-ATAICGITTT-CTGAATAT2 P GAOCG ^GTG-lkAAAGCATTTA ATTACCAACACGCATATTCC-ACCAATAAGCAkATTATTCCGATGACAGGTZGGG ACAmGAATTCTATCTTTCATTTTATAGTGGAT-CTATGATGTCTATTGCAGGTG, aAITTTTATTTGAAI AO7ATATA'AGAAA TCTACTGATATATCTAGAGAAAAAGATTAA 35 ORF amidno acid :e~ee(9IDNt17 M'RKYQKF SKI 1.TLSLFC-LSQI ?LNTNV,,LGESTVPENGAKGKLVV,.KKTDDQNKPLSKATFJL7-KTTAH PESKI S KVTAELTGEATFDNLI FGDYTLSFETmAPECYKNQTWQVKV-,ESNGKTT 1QNSODKNST ICQNW4ESLDKQY? PTU-,YDTKSSYKLEHVKGSVPNGKSSAK AVYFIYSSEGE{IRESI PSGTLSKRI SSVGDLAHNKYIELTVSC KTIVSPVDKQK PLDVV7FLDWISNSMNNDCPNFQRRNK,-AKKAAEALG TAVKD1 LGAN4SDNPV ALVTYGS DI AD 40 GRSVDWI{GFKSDDKYYGLQTKFT IQTNiYSHIKOLTN,4NASS IISRI PTEAPAAKWOiSTTNGLTPSQQK-QYYL; SKVGSTF7TNKAFMEADDI LSQVDANSQKI I VIITDGVTASYAI NNFKLCASYSSQFEQNKKNGYLN' KSNFL; LTDKFSDIKCNGSSYFLFPLDSYQTOI ISGNILQKI LYLDLNLNYPRCT 1 YRNGPVRSHCTPTKLY INS LKQK bWDI ANA-(iDI SAWRQWNSY!IDYKXNQDGT-QKLKSAFS-wLSDSS ITSLMS$,FSSKISYYTP 1VTSSDASNNS. 4 I LSKIQQQFSKVILTKSNS IVIOT IEDt't40K-,?1 QLGNGQTLOPSDYTLQGNDGS ISES IA TCGPNNDiGI 45 LKGVRLEYI SNKLYVRGLNLGSCQKVTLTYDVFLPDSFI SNKFYDTNGRT-LNPlSSDPNT -LADFPI PSIAD VREYPT ITTSNTKKLCS I FTSVDSDNSLLLKG,-ATFSLQSFNEDYKLYLPI KNNNS.KVVTSSNGKI SYSOL SDGSYQLI SAVSPKDYQKITNK?1 LTFSVVKGS Q10.1 IANKQI SEYIHSEGDSIILI TNT- 1P25011 EXTOG SGILSFTUOIGSI4MS IAOAIYIIKRhSSDISPEFKD 50 Strain IC289 OAF DNA s ece (SEQ ID NO: 217) ATGAGAAATACCAAAAAkPTT TTCTAIAAT ATT GACGT TAAOTCTTTT TTTTTGTOOAAALZITACC^GCTT-AAtT ACCAA7,TGTTTTAGGGGAAAG7TACCGTACCGG AAA2ATGGTGCTAAAGSAAAGTTAGTTGTTAAAGACAGA, T GACCAGA ACAAA3%CCACTTTCAAAAIGCTACCTTTGTTTTAAACCTACTTCACACTCAGAA'AGCAAA.zGTAGAA 55 AAtAGTAzACTACTGAO-GTAACAGGTGAAGC-TACTT'TGATAATCT-CAC ACCTGGAGATTACACTTTATCAIGAAP GAAA7 CGGC-ACCCGAA %GGATACr7 AAAGAACTACCCA' GACTTGG CAAGTTAAGOTTGAGAGTAATGGAAAAA.CT AC. GATACAAAATAGTGATGAT -AAAATCTATAA tTTGP.AAAGGCAAG7A(GACTAG AT AG'CAGTATC-C CTTACAGGAGCTTATGAAGAT42AAAPAGAATCTTATAAsTCTTGAGCATGTTAAA.AATTCAATTCCAA 'ATGGG PATTAGAGCAAAk~GCGTTATCCATATTCAAGTGAAGTGAG-ACATAAAGAzATTCAAGAGGAACA 60 T-TATCTIAACG TATTTr-CGAGTAAATGATTTOGATCATAAT.%'AAATA TAAA-TTAGTTAC TGT TGCGGT - 120 AAUTCC .4TAAT~kA.IACT. ,AAAATAAAG.rATGAACCTCTG.GATGTTGTTTTTGTTCTTGAPTAAT'TC AkATTCT AT GAAG.AATAATGGAALAATACAAGGCAAAAA GGCAGGTGAGCAGTAGuAAAT TAT AAMAGATGTTI TTAGGAGCAAATGTTGAAAACCGA GCAGCTTTAGTTACTTATGGTTCAGATATT-TTCATGGAAGGACAGTT AAA,,GTTATAAZ AGGTT TTAAAGAGGATCCT TA'TTATGGAC TTG AACTAGTTTCACAGTTCA'GA-CAAAiTG AT 5 TATAG-CTATAAAIAGTTACTATATTGCTGCTGATATTATA-A.AP4AGATCCCTA; AGAAGC,'TCCAGAAG;CT AAGTGGGGGGCACAAGTC'iTAGGA!TTAAIPCTCCAGAAAiuAAA GAGGGAA, TATGrAT ± TAAGTAAAGTAGGTGAG ACCTTTACAATGAAAPGCTTTTATGAGGCAGATACCTTGTTAAGTAOTA'TACAGCCGTAAGAGTAG.AAG ,CATT ATW-GTTATC"TAACTGACGGTGTTCCAACAAPGATG'ATATGC-CATTTAAhGTTTTGT*AAAGOTTCPAC"ATAC(' GCAAAsTCAAtTTTGAGAGAATAA&PAAMAAGGTTAiTTTAGACtAAAATAATTATTT TATAACTGATGATCCA 10 OAAAAkGAT CAAAGGCAATGGOGAGAGT TACTT TTTGTTTCC-CT TAGATAGT1TAT CAAACAC-AGATAATTTCT OGAAACTTACAAAAJC TTC AT TAT TTAOATT TA;ATCTTAATTAC -CCTAA-GGTACAA TTTATAGAPAATGOA CCAGTAAG AGAACATGG~zAAG-ACCAACC-.AAC'OTTTATATAAATAGT TTAAAkCAGAAAAATTAT GACATCTT T A ATTTTGGTATAGATATAT CTGGTTTTAGACAAGTTTATAATGAGGATT-ATAAGAAATCAIAGATGGTACT TTTCAAAAAUTTGAAGGAGGA.A %GCTTTTGTh.ACTTTGAOAATGGGGPAATAACAGiAACTAATGALATTCATTCTCT 15 TCTAAzACCTOiAGTATWATACCCCGATAGTAA CTTCAGC G~ATGTATC-TAAT AATGA AATTTTATCThAAATT CAGCAkACAATTTGAAAAGATTTTAACA.AAGGAAAACTCAATTGTTAATGGX;ACTATAGAAGAT CCTATGGOT GALAAAA TCATTTA' CA~TGTTGGC~zAGGAnC.AACATTQCAA~zCC AGTGATTATACTTTACAGGG~.A .ATGAi T ,GGAGTATAATGAA- hGATAG-CATTGCAACTGG-AGG-GCCT.2'ATAATGATCGTGGrGATACTTA.AAG(GGITAAAi TTAGAATACATCl-AAATAAA;,CTCTACrGTTAGAG rGTTTGA lACTTAG'GGAGGGGCAZAAAAGTAACACTCACA 20 TATGAPTGT GAAACTAGA-PTGACAGTTTTATTAGTAkACAAkAT TCTATG;ACACTAATGGTAGA-. ACA.FCATTGtAT CC AA)-VTCAGACGGz'AACCGA TACACTTAGAGATTTTC-CAAlTCCCTA2AAATTCG-TGA TGTGACGAAATATC.CT ACt ATAA.CGATT.AAAACGAGAA!Gi'AOTTAG7GTGAAA TTGI,'ATTTACAAAAGTTGA TAAAC,(ATAATAATAAG TTGCTTCTCAAAGGAsGCTACATTTGAA4CTTCAAGA' ATTTAkATGA4ThATTATrAACTTTATTTACCAATAA-A A-ATMA:ATTCAAAPAGTAGYTGACGGGAG AAACGGCAAAATTTCTTACAA AGATTTGAAGATGGCAAA; TAT 25 C-AGTT AAT AGMCCAGTTTCGCCGAAG GATTlTCAAAAAAUTTACTAATPtXACCAAtTTTTAAC-TTTTGAAG CTT GTTAAAGGATCGATACAPAAATATAATAGCTGT TALATAA-ACAGATTTCITAATATCATGAG3AAGGTCACAAC, CATTTAMITACCAA,7CACCCATATTC StCCAAAAL-GAATTATTCCGATGA CACTGCGAA.AGGAATTCTATCT TTCATTTTAATAGCTCCAGCTATGATOGTCTATTGCAGGTQG;ATTTATATT TGAAAAGA2^,ATAA'GAAA :TCT AGTGCATGCATCAATCCAGAA-AGATTALA 30 OFF amino acid Baguence (&EQ lD NO, 198). MRKYQKFSKO LSLLQIPNTVOSTV 'ENGAAOKLvVKK' TDDQ KC-LSKATrVLKPTSESESKVE' KVT TEVTO EATFONLTFCOYTLSEETAPEGY J(TTQTWeQVKVESNSKTT IQNSDDORS II EQRQEELDKQYF :TOAYEDTNFSYNLERVKNS :r FGKLEAKAVWl NFYS SEGEIIE IQEOTLSRRI SEVUDLDHNKYKJ ELTVSG K S I I XT INK E SLDVVFVFLDN SNSMKNNGK. WRAKKAGEAVET I I KDVLGANVENR.AAL7T YGSD I FDGRTV 35 FYI -KGFKEDFYYGLETSFTVQTNOYSYKKFTNI AOI IKEKlPKEAPEAKEGGTSLGL 'FEKKRE"DLSKVGE TFTMKAFMEADTLLSS IQRKSRKI IVHLTIDCVPTRSYAINSFVKGSTYANOFE.RI KEKGYL.DKWNfYFI WOOF S.' K RNGESYFLFz PL'DSYQTQII1SGNLQKLW4Y LDLNLWL PKGT I YRNUGPVREXGT PTYLYI NE,-LEQENYDI F NFI DI SGzFRQVYNEDYKK 'QDGTFQXIJKEEAFELSDG I ,?,TLMNSF-SSI PEYYT PIVTSADVSNNEI LSKI 2)05551 LW KENS IYNGT IEDPNGDKINLHLGNGQTLQPSDYTLQGNDGS 114KDS5IATGGPNNDCGGILEOVE 40 LEINLVGNGGKTTDKOSISNRFYDTNGR.TTLNPKSEEPDTLRDFP I PKIFDVREYP TI TIKNEKKLGE IEFTKVOKDNNKLLLKGATFELQEFNEDYKLYLL'IKNNNSE~VVTGENGKI SYRDLED)GEY QLIEAkVSPKDYQK ITNPI LTFEVVnKGSIQN I IFYIEQI SEYHIEEGDKM'I TNiTE{I Pr1(01I PMTGGRGI LS,' FILIGANMSIAGGIYIWEiKESSDA SIERD ___________ 45 Strain 1C291 OFF DNA serntence (SEQ ID NO: 21D ) ATQAGAAAATA.CAAAATTTTCTAAAA2UTATTGACGTT AAGTCT TT TTTGTTTGTCGCAAATA-"COC'TT-AA'l ACCAzATGTTTTAGGGGAAGTACCGTACCGGAAAATGGTGC TM AUGGO AAGTTAG CTTGTTA JkUAAG;ACAGAT GACCAGAAYCPAAACCACTTTCAu'AAGCTACCTTTGTTTTAAAeAACTAkCTGCTCATCCAAAA.PGTAA.ACAGA-A 50 A AAGTAACTG CTGAGC-TAACAG GTGAAGCTACTTTTGA 'TAATCTCATACGTGGYAGATTATACTTTAT CAGAA. GAAACAGCGCCCGAAGGT TATAAAAGACTAACCAGAC TTGGCAAGTTAAfT TGA'G"TAATGGAAJCT ACGATACAAAAT",'XAGTGGTGAITi'AMA LTOCACAATTGGACAA AATCAZGGAAGAACTA GATAAGCAGTAT-CCC CCCAC-AGGAATTTA!%TGAAGA. .;TACAAA, GGAATC TWAThA-ACTTGAGCATGTTAAA -GGTTCAC-TTCCAAAT'GGAZ AAGTCAGAGGCAAAAG UCCAGTTA.ACCCATATTCAAGTGAAGGTGAGCATATAAGAGAAAkTTCCAGA(GGAACA 55 TTATCTAAACGTAkTWTCAGAATAG-;,CGTGA.TTTAG;CTCATAAT.AAAT ATAAAA -TTGAGTTA ACTGTCAGTG-GA AAACCATAGT.AAA ACCAGTGGACXAAGAAAGCGTTAGATGTTGTCTT T cJk uGGICTCGATAAT TTAACTCA ATGAATAACGATGGCCCAAATTTTCAAAGoGCA TAATAAA7 GCCAAGAU..AGCTGCCGAAGCTCTTGGGACCGCA GTPAAGAT ATTTTAGGAGCAAACAGTGATAA ',T-(' m r GATTAGTTACCTATGGTTCAGATATTTTTGAT GG TAG-GAGT GTAGATGTCO-ZTAA A AGAT TAAGAAGA.TGATAAA;TA'TTATG GCCTTCtAACTAPAG TO^AC-A 60 .TTCA ,GAGAGAGATTATttGWATAAA CPJT TAACAAATA-ATGCTGAAGAGAkTTAT AAAAAGGATTCCGAOA -121 GAAGCTCC'fAAAQCCTAA-GTG'GS3ATCTAC'TA'CCI-dGGATAACTCCAGC-CAACAAAArGGAGTACTA1CT1T AGTAA. AGTAGf.GAGMV.ACATTTACTATGAAAC;CCTTCATGGAGSCAGATC3ATATTTTG AGTCAAzlGTAAA11"TCGA A ATAGTCAXM V AATTATTGTTCATGTAA2 CTGATGGTGTTCCTACGAGATCATATGC-TATTAATAATTTTAA C TGGGTGCAiTCiVrATGtAGCC-AT TTGACAAA TAUVnAAAATGGATATC TAXATAAAAGAATTT TCTA 5 CT-TACTGNTAAGCCCGA.GGATATAAAAGGAAATCGGGAGAGTTACTTTTTGTTTCCCTTAGATACTTATCAA"' ACAZCAGATAATCTCTGGAAAzCTTACAAAAACTTCATTATTTAGA.TTTA.A ATCTTAATTACCCTAAAGGTACA TTTTATCGAAATGGC'AGTAAA3PGAACATGGAkACA.CCAACCA-AC-TTTATATAAA-TAGTTTAAAVACAGAAA AZATT ATGA4CATCTTT AAT-TTSGTATAG~ATATATCTGGTTTTAGACAA431GTTTATz ATGAGA %TTATAAGAAA ?ATCAAG-ATGG TACT-TTTCAA7AAATTGAAA kGAGGAPAGC'TTTTG AA.CTTTCAA3YTGGGGAATAACAGAACTA ACATGAAGTCnTTCTCTTCTAACCTGAGTTTATACCCCGAtTAGTAACTTCATCCGATGCATCTACA.TGA. ATTTTATCTAAA ATTCAGCAACAA ,TTTGAAAAG-ATTTTA.ACAT-AA-AAACTCAArTTGTTAATGGAACTATA GAGATCCTATSGGTGACAA AATCAATTTACAG3CTT-GGCAACGG3ACAA-ACATTlGCAACGAAGTGATTATACI-T TTACAGGGJAATAIGGAAGTATAATGAA.AGATAGCAT TGCAACTGGTGGGCCTAATAA' TGATGGTGGAATA CTT-AGGGTTAA-TTAG&T'ACA TC- iPATACTCTGTTCAGTTTGPIACTTGGGAGGGACA 15 A.GTAAkCACTCAC-ATnTGATGTGAAAC TAG~ATGA2CAGTTTTAT..ATAACAAA-TTGTATGACrAC-TAATGGT £AGiACAAICATTSAATCCTAAA-TCAGAGGATCCTATApCACTTAGAG STTTTCCAATC(-CCT2AA ATTCGTSAT AAA'GATAATAATAAGTTSCTTCTfA -GG GTACGT'-TGiAAC TTCAAG>AATTTAA6TGAtAGATTATAkAACTT TATTTACCAA.TAAAAAPJ-ATAkATAATTC^AAAA GTAQTGACGGGAGIAAA!CG GCAA-AATTTCTTACIAAGATTTG 20 AAA(;GATGGCAAATATCAGTTAA.TAGALAGCAGTTTcGCCGAA.GGAtTATc-PAAAATTACTALATAAk(CcAATT TTACTTTTGAAGTTGTTAAAG;CGATC-GATACA~aAAATATAATASCTGTTA. AAAC -AGATTTCTGAA±lATCAT GAGkrGAACGSTGACAAGCAkTTTAATTAC-CAACACGCATATTCCAC CAAAAPGGAAPTTATTCCGATGVACAGGTGGC AAkAGGAATTCTATCTTTCATTTTAAkTA GGTGGAkTGTATGATGTCTATTGCAGGTQGAA.TTTA ,TATTTGGAAAA AGATATAAGAAATC-TAGTG ATATATC TAGAGA.AAAGA TTAA 25 QEF ami-no acid sequpence (SEQ 1D NO; 1299): KVTAELTG EATFDNLI PGDYTLSEETAPEGYKKTNQT! QVJKVESNGKTTIQVNSGDKNST IGQNQEELDEQY P PTG1 VEPTEESY KLEHVKEGSVP'NG7KSL&AKVNt,',PYSSESERI SEXPEGTLEFRI SEVGDL ANNK'FYKJELTVS1G ET IVKPVDK QKPL-DVVFV- LDNSNSM~lNDGPNFQRH-NKAKKA.A4EALGTAVXeDI LGANiSDNRKVALVTYGSDI SD 0GE.SVDW ,KGFKEDDKYYSL QTKFT XQTEN? SHKQLTNNAEE II SRIPTSAPKAKWGSTTNGLTPEQQREYYL, SKVGETFTMKAFMEADDI L-SQIVNRNSQK I 1VHVTDGV2TRSYAINNFSrLGASYESQFEQN IKNGYLN~lKSN:FL LTDK PEDI KGNGESYFLFPLDSYQTr II SGNLQKLIIYLDLNLNY PRGTFYRNGPVREHICTPTKLY INSLKQ< NYDXSNEGI DI SGFRQ wVY 4EDYKKNQDGTFQKLKEEAFELSDGE ITELkLKSFSSFAFEYYTPIVTSSDASNNE ILSKIQQQFEKILTKENSIVN--TEDPMGDKNLQLGNGOTLQFSDYTLQGNDGSlIKDSIATGGPNNDZGI 35 LSGVKLEYX RNKLYVRGLNLGEGQRVTLTY DVSLDDSFI SNKFYDTNGPJTL(IPKSEDPNTLRDFPI SKIRD 'VRPEYPT -IXKNESELGEX EFTRV DKDNNKLLLKGATFELQEFNIEDYKLYLPI ENNNSKVVwTGENGKI SYKDL KDGKYQLI SAVE PKDYQKITNKPI LTFEVTVKGS IQNI I-AVNEQI SEYHEEGKi{LI TNT H PPE I I PMT GG KGI LSFI LIGGSMIS IAGG I Y IWSRYKKSSDIT SPEEKD 40 Strain 1C304 O~lSDNA ea~nce SEQ 12) NO: 219) A TG AGAAAUATACCM?,ATTTTTCTAAATATTGACGTTAlAGTC-TTTTT GTT-GTCGCAeATACC GCTTAAT ACGAkATGTTTTA^iGGGGAAi~zAGTAzCOGTAC,'CGGAA?.ATGGTGCTAAAGGAAkAG,'T T?.GTCGTT:,AAA. JAGACAGAiT GACCAGAACAAkACCAC^TTTO-AAAkAGCTACCTTTGTTTTA,AAACTACTGGTCAACCAGAA.t AGTA.AAATAGAA3%. 45 AA.A2GTAlACTGCTGAGOC3T'AAQAGG-TGA AGCTACTTTTGATAATCTCATA CCTGGAG ATTATACTTTATC.AC-?2 OAA,CAGCGGICC(AGTTATA;AAAGATAACCAATTGGCAACGTTAGGTTAAGTAATGGA-AAA.CT ACG ATACAAAATAGTGGTGATAAAAJ-iTTCCACAtATTGGACAAA 1ATCAGGAAGAAGTAGATAAGCAOTATCCCI CAClAGGAATTTATG& AGAO.AA7AGGA; ATCTTATAA,-ACl-T ,GATGTXTAAA GTTCAGTTCCAAA TGG7A A AGTC-A'AGCAsAAGCAGTTAACCCATATTCA AGTOAAGGTGAGCATATAAOAGAA. iTTCCnGAGG3AAGA 503 TTATCTAAAGGTATTTGAGAAGTAGGTGATTTAG,-CTCATAATAAATATAA 6AATTGrAGTTAACTGTCAGTGG A AAAACCATAGTAAAA.CCAGTGGACAACAAAzAGCGGTTAGnTGTTGTCTTCGT-ACTCGATIA%TTCTAOTCA' ATGAATAACG;ATGG CCCTAATTTTCAAIAGGCATAAPTAAt'AGCGAAGVAAAGOTGCCG AAGI2TGTTGGGAkCCCCA GT,3-AAAGATAT'TTAGGGGAAAOAC&Y TArTATAGGTTGCATTAGITTACCTATGGTTCAGATATTTTTGAT GGTAG GAGTGTAGATGTCGTAAAA-AGGATTTAGAGAAATAGCTCACTATGA 55 ATTOAGACAGAGAAVTTATAGTOAT-AACAATTAAVCAA'IATGCGA GGA TATAPA~tAGGATTCGGACA GAkAGCTCCTAAAGCTAAGTGGGGATC TAO TACCkAA TGGATTAACTCCAGrAGCA ACAAA. AGGAGTACTATCTT IAGTAVAAGTAC-GAGAAACATTTACTATGAAAGGrCTTCATGGAGGCAGATGAITA-TTTTGA.GTCAAGT AA.'ATO-( A AiATAG'rCAAAA,'JATTATTGTTOATGTAACTGATGGTGTTCCTACGAGrn GATATGQTATTAAT AATTTTAAA GTGGGTGC-ATCATATGAA'sAGCAATTTG>AAA.AATGAAkAAA.AA.ATGG3ATATCTrA 4 ArTAAAtAGTAzATTTTCTA 60 CTATA, A7CGG7TA 2 PG~~TGWA-AcTTCTTGTCr, SGTGmATCA - 122 ACACAGATAATCTGTGGAACTTACAAA;AACTT-CATATTTTAGATTTAAATC-TTAATTAO .ITAA2 AGGTA CA TTTTATCG7AAA TOGA CCAG TAA CGGAACATC GtAACACCAACCAA.ACrTTTATATAAA-;TAC TTTA-AAAC^AC7A-AA A.ATTATGACAkTCTTTAATTTTGGTATnGATSITATCTGGTTTTAGkC'A.G TTTATAATGAG;A.TTATAAGAA.A AATCeAAGATGGTACTTTTC?2AAATTGAAzGA.GGAGCTTTTGAACTTTAGATGGGGA2 ATAACAGSAACTA 5 ATGAkAGTCATTCSCTTCTA.AACCTGAGTATTATACCCCGATAGTAACTTCATCCGTCATCTAACAATGAA ATTTTATCTh AAATTCAG-AAC-AATTTGAAA,-AGATTTTAAC;AAAAGfAAAACTCAAT-TGTTA3%ATOOAACTAT A GAAGATCCTATGC-GTGACAAAATCAATTTACAGCTTGGCAACGG ACAAA CATTG-CAA,,CCAAGTGA TTATACT T TACAGGGA.OLTGAQAGAGTAAATI-hA GT AGC AT TCAATGGTGGGCTAATAAT GAT GTG-GaAA CTTAAAGGGGTTAAzATTAGA'lATAC-ATCA.A.kAATAAA"CTOTACGTTAGAGG TTTGAACTTA GGGGGGACAAk W0 AAA4GTA2ACTOACATATGA1-TGTGAAUACTAGTGACAGTTTTATAAGTAACA AATTCTATGA, CA CTAAITGGT AG AACAACATTOAA,4TCC TAP kTrAGAGOATCOT AATAOAOITTAGAGAT TTTOCAATOOCCTAAAATTCOrTCAT QTGAG AGAATATCCT ACATi'AACGATTAACGC-AAiGA:GTTIGT-GAAATTGAATTT ACAAAAGTTGA T AAkAGAT ATAATAAGl TTGCTTCTCAMVGAGCTAC(STTTGAAiCTTCAAGAAi;TTTAATGArAGATTAiTAAA-CTT TATTTACCA PJNAATA ATAATATCAAAGTATAGGGAGAAA,4CGGCA AA'TTTCTTCrAAAD",ATTTG 15 AAAGATGGC.IAAATJCAG~iTAATAGA AGC-AGTTTCGGCGAAtJGGgd.TAITCAAiAAA TACTA, TAAP .OAAT TTTACTTTTGAADGTTGTTAAAGGATCG'ATACAIATATA6ATAGO-TGzTT AATA.AA(,CATTTOTGA.ATATCAT CAGGAAGCGTGACAAG.rCATTTAATTACC -AAC-ACGOATATTC-CACC AAAOOGAATT-ATTCCGATGA.CAZGOTGGG AAAGGAkATTCTATCTT2'CAT'-TTA-ATAGGTGGAkTCTATGATGTCTATTGCAGGrtOGATTTATATTTGG-2AA AGATATAAPGAAA,,7TCTAGTGA.TATA.TCTAGAGAAA GATTAA 2 0 ORF arntaocid spauence (SEQ ID NO: 200) M?.EYQKFSKI LTLSLFCLSQIPLNTt ThLGESTVlPENIGAKGrKLVfl TDDQNKPLSKA7TFV LKTTAQPESKI 'E KVTAELTGEATFDNLI PGDYT4LSEETAFEOYKKT. QTWQVKVESNCK-TT IQNSGDKNST IGQNQEELDKQYP STGIYSDTRESYKLEHV KGaVPNGKSEAFaI ,tPYSSEGEHIREIPEGTLSKRISEVGDLANNKYEIELTVSG KT IvRPVDRQKPLDvvrIqLDNNM, NDGNFRHNKAKRAE~ALS6TAVKO)ILGANSONWRA LVTIYG S DI T 25 GRSV DVV'KGFKEDDKYYGLQTKFTI1QTENYSHXQLTNNAEE' I RI PTEAPEA KWGSTTNGLTPEQQKEYYL LTDKPEDIKGNGESYFLFPLDSYQTQIXSGNLQRIJHYLDLNL41NYPRGT"F'YRGPVREFRGTPTKLYINLt,'KQE NYDX VNFG IDI SGFRQVYYNEDYKKNQDGTF'r, LEEEAFEL.SDGEI TEL!IRSFSSKPEYYTP IVTSSDASNcIIE I-LSKIQQQFEKILTKENSIVl~NGTIEDPMGDKINLQLGNGQTLQPSDYTLQGNDGSIM .DSIATGGPNNDG-GI 3110 L OVKLEY 1' NKLYVRGIAI LGEGQKVTLTYDVI LDDSFI SNRFYDTNGRTTLNPKSEDPNTLRDFP I FI RD RIYKYQLIEAV',SFKDYQ--KITNKPILTFSVVRGSIQN IIAVNR iQISEYZE-GDKLITNTIIIFPEKOI IPMTGO ROI LSFILIGGSMNSIAGXYIWKRYKE{SSDISREKD 35 Strain IC305 ORF DNA sequence (SEQ ID NO: 220}: AT GAsATACCAAAATTTTAAAUTAT TACTTAGTACTTTTTTGTTTGTCGCAAATACCGCITiAAT ACQAATGTTTTAGGOvGPJ;AGTACGTACCOGGGjTG- -CTIPAGA~zAAGTTATTGTTAi' AACAGAPT GACCAG--CAAACCACTTO-AAGCACCTTTGTTTTe.AAAOTACTGCTATCCAA AAGTAA' AGAAZ 40 AAAO TAAOTGCTC-AOCAC.. GGTGAA GCTA CTTTTG ATAATCTCATA-CTGGACATTATACTTTAT CAGAA GOAA.CAGCGCCCGMV5GGTTATAA,AANACTACCAACTTGGCAVGTWAAv-GTTGG.CAGTAATGGAAAACT ACG ATACAAA-DATAGTGGTGATAAPAATTCCACAkATTGGACAAAATCIAGGAA.GAAOTAGAnTA~AGCAGTATCCO CCCAICAGGA.ATTTATG AAOATAC AAAGGAATOTTATAAAi CTTGAGC-ATGTTA~zAOGTTOAGTTCCAA-ATGGA A.G"AA G~A,.,GATACCT TA GCAGTA AAACA77-TC-CAGAGGGA;ACA 45 TTA7TCTAAPCGTATTTAAAGTAGGTGATTTGCTCATA TAA6TA-AAAATTCTTA2ACTGTCAGTGGA AA..hACOATAG 2AA-ACCAGiTGGA tCAAA CAM 'AG(CCTTAGATGTTG3TCTTCGTACT CGATAATTCTAA' CTCA ATGAPATAACGATGCCAAA.TTTTCrAUGGCATAATAAA.CAAA.AGCTGCC-CAGO GTOTTGGA COOCA GTAAAAkAGATA TTTTAG GAGCAA;6ACAGTGATAATAGC-GTTGCATTAG TTACCTATGGTTCAGA TATTTITGAT GGTAGGAGTOTA2GATGTGGTAJAAAAGGATTTAAAGAkAGATGA-TAAAJTATTATGOCCTTCAAAOATAAzGTTCACA 50 A.TTCAGACAG AGA ATTATAGTCA TAAACAATTAACAAATAATGCTGAAGAGATTATAA AAAGSATTCCGACA GAkAGGTCCTAkAAGCTAIAG'TGGGGTTCTAO^TACOAATOG(ATT AQTCCAG AGCAACilaAAAGGAGTACTATCT A-GTAAAGTAG' GAAAOATTTAC TAT AAAGOOTTOATGGAGcGCAGATOATATTTTGAOTCAAGTAAATCGA A ATAkGTCAAAAZ ,I TTTTGTTCATGTAACTGATGGTGTCCTACGAGATCATA GCTATTAA21TAATTTT.AkA CTGGGTGCATCATATGtAASCCAATTTG'ACAA . TGAZiAAZLAATGCATTCTAAAPT-AAAGTA. TTTTOTA .55 CTTACTGATAAiGCCCGAGGAYTATAAAA JGG AAAT GGCGAT-GAGTTACTTTTTGTTT-CCOTTAGATAG-TTATCAA ACACAGATAAkTCTCTGGAAiACTTACA'AAACTTCATTATTTAGATTTAAA7'TCTTA-ATTACCCTAAA4-GGTACA TTTT ATCGAAATGGAC CAGTA.AGAGAACATGGAACACGAAG1CAAAkCTTTATATAAAl-TAGTTTAAA;CAGAAA' AATTATGACATCTTTA ATTTTGG TATAG ATATATCTGGTTTTAGACAAG TTTA -ATGA.GG ATT TAA GAAA AATCAnGATGGiTACTTTTCAA.AAATTGAAIVAGAIGGAAGCTTTTG AACTTTCAGAT4GrGGAATAACAGA ACTA 60 ALTGAAGTCATTCTCTTCTAAAC-CTGAGTATTAA2 CCCCGATAGTAAC TCATGG ATGCATCTAPCAiATGA -123 IA TTT TATCTnAAAAT TC AGCAAC AAT TTOA~TGAAAAGA Ak.-AAAC ,-TCA.TTGTTA.AtTGG AAMTATA IGAAGP~ATCGCTATG GGTGCAAAA ,.%-TCAATTTAGAGCTTGGCAACGzGACAAACATTGG-'ACC'AAGTGnTTATAGT TTAAGG7AATGATGGAAGTATAAtTGA-AAGATA GG-ATTGCAACTGG,"TGGGCC'TAATA'4ATGATGGTGGAA TA 5 AAAGT 1 ACACTCACATATGAJGTGPAACTAGATGA CAGTTTTATAAG TAAC AATGTATGACACTAATGGT I AGAAGPJI&'ATTG nTCCTA ACGGACT;.AATAAATTCACCA-AICTA GTGAGAGAATATCCTAOA ATAGC-GATTAAk .ACGGAAGAAGTTAGG-TG;AAA TTG-AATTTACAAAAG(TTGATX At.ArATAiTAATAAC TTIGCTTCTC;AAG1GAGCTACGTTTGkk CTTC'ACPAATTTAAT-'GAAGATTATAA,,AGCTT TTTTACCTAAA-ATATAATTAAA.-iAGTAlGGACGG(GAAAAGGGCAAMkATT TGTTACAAAGATT TG 10 AAAGATGG CA AATATCAG3TTAAiTAGA-xAGCAGT TTCGCCGAAGGAPTTATGAAAAAARTTACTAAT AAAzCGA, ATT ITTAACTTTTGAAG TOTTAAAG' GATC0ATA~CAMATATAAkTAOCTGTTAAlTi AAAGATTTGTGAIATA'IOAT GAGGr.AAGGT'GACAAGCATTTAATTACCAACACGCATA'TTCCACCAzIAAGGAATTATTCGGATGACAGGTGGG AA.AGGAATTCTATGTTTCATTTTAAZ TGGATCTATG ATGTGTATTGCAGCGTGGAkATTTATATTTGG AAA AGATTATAGA AATCTAGTGATATATCTAGAGAAAA ,DAGATT-AA 15 ORE amino acid se;F,, (SQIDNl;21 NRFYQFFSKI LTLSLFC-LSQI PLNTNP7tGESTVPENG AFGKLT,% XTDDQN PLSFAiTFVLFTTJ) PESFI F KV ,TAELTGEATFDNL IF0DYTLSEET APEGYFKK'NOTW"eQVFV"iESNGFTT IlQNSGDKNST IGQNQEELDFQYP 1401 YEDTI FST LEHVKGFCSVPNGKSEA, AVN1PYS SEGENIEIlPEGTLSFR'I SE'VGDLEENF YKIELT VSG KTIVKP-VDFKQKP-LDVVFLDtNSNSMINNDPN FORHNFlAKKAAEALGTAVKDI LGnN4' :)NRALVTYGSDlFL) 20GRSVDVVFKGFKEDDKYYGLQTFFTIQTENYSIIKQLTNNA-EEII FRI PTEAPFAFKWGSTTNGLT PEQOREYYL SFVGETFTMF4AF-MU0DI LSQVtIRNSQFI XVMVTDGVPTRSYAI NNFKLGASYE SQF QMKKGYLNFSNFL LTDF'ED1 KGUGirESYFLFPLDSYQTQI I SGNLQFLRYLDLWNYPFGTFYPRGPVREGT PT FLY INEL KQK FY01 'ERGlDI SGFRQVYINEDYFFNQDGTEQFLFEEAFELSDGE ITELNK!FSFSSFPEYYTP IVTSSPASNNE I LSF1QEQEKI LTKENS IVNGT I LPllfGOF LLNQLPSYLGDSiFO TGNDG 25LKGVFLEYI KNFLYVRGLNLGEGQFVTLTYDVKLDDSEI SNKFYOTNGRTtILNPFSEDPNTLRDEPPI 1RD VREYPTTI KNEKFLO ILEFTFVDFDNNFLLLKGA7FELQEFNEDYFLYLFI FJNNSKV VTGENGF I SYFOL EDGFYOLI EAVSPFDYQFI TNFILTEEV'%VXGS 151ITAVNKQ ISEYREEGOFI-LI TUTHI P2KG IiPMT'G EGILEFI L100GSNNSIAGGIYIWKRYFKSSDISREXD 30 Strain 1C306 ORFjDNAzeuence JSEQID NO: 221I: AkTGAGAAAATACCfATTTTCTAAATAT.-GCGTTAGTCTTTTTTGTTTGGG'-CAA~i TACCGT TAAT ACCAATGTT TTAGGGAAAtUGTACCGTAC CGGAAPAATGGTGC T-AAGGAAAGk' TTAGTTGTTA? A-'GACAGAT GACGAGAACAAACCAGTT TAAA,A GTACO-TT-TGTTT1AACACIACTGCTAT' CA;GAA GTAAATC-GAA 5 A,AG TAACTCCTG3\GCTA, AAGTGAA GCTACTTTTGATA ATCTO ATACCTGGAGzATTATACTTTATCnGAA GAAXACAGCGGCCGAAzlGGT TATA-AAAG ACTAACAGACTTGGGCAAG-,T TAAGGTTGAGAGTAMTGGAAAAAGT AC-GATkACAAAATAGTGGTGATAAAAkT TCCA2CAATW-GGLACAAAAiTCAGGAkAGAA'CTAGA 'TAAGkCAGTAT'-CGC CCCACAGGAAiTTTAT- GPGTACAA, AGG aA.TCTTATAACTTGAGCATGTTAAAGGTTC-AGT CCAA TGGA AAGTCAGA.GGC -AA(ACAGTTAAGCCATATk'ITCAAGTGAAC i %GGTGAG3CATATAG.AGAATTCCAGAGG AAC-A 40 TTATOTAAAC-GTATTTCAGAAG TAGGTGATTTAG CTCATAATPAAAT2AMAMTGAGTTAOTGTCAGTGGA A.AAACCATAGTAAA~zACCAGTGGACA~zAAAAAAGOCGTT , TGTTGTCTTCRTAGTC-GATAATTCITAACTC-A ATGLATAACGATGGCOAAATTTTCAAAGGCATAATA,-AGCCAAGAAGCTGCCGAAGCTCTTGGVGACCGC-A GTtAAGA; TATTTTAGGaAGCAA ACAGrTGA.TAATAGGGTTGCATTAG.rTTACCT--IATGGTTCAGATATTTT TOGAT GGTAGGAGTG3TAG2ATGTCGTAAAAtGGA'TTTAAA,- GAAGATG'AT AAATATTATGGGCTTCAA' ACTA AGTTC-AC A 4-5 ATT-CAG-ACAGPAAATTATAGTCAPTAzAGAATTAACAAATAATGG-TGAAGAGATTA.TAAAA ,*AGGATTCCGAQA GAAGGTCCTA-AG-CThAiGTGGGGrATCTACTAICCA.a.TGGATTAACTCOAGAG CA~-AOAAGGAGTACTATGTT AG TAALbGTAGGAG;AAAGATTTA 4CTATGAAAGCGTTC:ATGGA GGCAGATGA TATT14GA, GTCAA GTAAATCGA AAkTAGTCAAAAAATTATTGTTCATGTAA ,CTGATGGTGTTCCTACGAGATCAT ATGCTATTAATAZATTTTAeA CTGGGTGGATCATATGAMAGCCAArTTTOAAiCYAAT-AlAAAAAAATGGATATCTAA4ATA7AAGTAATTTTCTA 50 CT TAO,'TGATAAGCCGGA-.' P-A .A?.TGGGrA.AGTTACTLTTTTGTTTCC'TTAGATAGTTATGCAA' AGACAGATSATCT TGGAAATT ACrPAA.CTTCAT TAT TTAGATT TAAATCT TAATTACCCTAAAGGTAGA TTTATCGA.AATGGAOCAOGTAA7 GAGAACATGGAA tCACCAAP5CCAA-,ACTTTATS ,TAAA TAGCTTTAAAkCAGAA .AATTATGACATCTTTA ATTTTGGTATA GATATATCTGGTTTTA2GAC.GAATTATM;,TGAGOATTATAAGAA AATCAAGATGGTAGTTTTCAAATTGAAGCAGGA AGGTTTTGAAC,-TTTCAGATGGGAAA,?STA-AG.AGAACTA 55 kTGAAPGTCM^.TCFCTT-TAAACCTGAGTATTATACOGCGA4TAGTMGA.TTCATCOATGCATCTAAC'AATIGAAk 'XT.TTTATCTAAAA-TTCAGOACACPATTTGPA-AAGATTTTAACAu4AAGAAACTCAATTGTTAATGGnACrTATA GAAGATGCTATGGGTG CAAMATOAAzTT-TACAGCT'IGGCAA ,CGG AOAAACATTG:CAACCAAGTGATTATA CT TTA'iCAGGG AAATGATGGAAGTATAATGA? UAAATAGCATTGCAYACTGGTGGGCGTAJTA-ATGATE5TGGA-1A 0TTAAAGGGGTTPkCATTAGAATACATCAAAAAA1XCTOTAGGTTAGAGGTTTGAACTTAGGGGAGGGACAA 60 AAAGTAACACTCACATATGATGTG AAACTAGATGAGAGTTTTATAA GTiAATTCTATG5ACACTAtATGGT -124 AG.AACA-PACATTGAATCCTAAATCASAOGA.TCCTAATACAC-TTAGA.GATTTTCCAATCCCTAAAAT 'CGTGAT GTGAGAGAATATCCTAC AATAAC GAT TAAAAACYGAGJAGAAGT TAGGTGAAATTGAT~jTTTACAAAAGTT GAT AAAZGATAJTAATAAGTTGC-TTCTCAArAGSAOCTACOTTTGAACTTCA2%AGPJXTTTAA. TGAAGATTATAA2ACTT TTTACCAATAAAQATAATAAT TCAMAGTAO (TGACGGGCAGAAAAkCGC-CAA7;AATTT4CTTACAJAGATTTG7 5 AAAG.rATGGCAATATCnGTTAATAGAGCATTTCGCCGzAGGATTATC~kW.AATTACTAIATnA;ACCAA-TT TTAACTTTTGAAGTTGT TAA-AGG ATCGATACAtAAATATAATAGCTGTWAATAA' ACAG ATTTCTGAPATATCAT OAGGAA,.GGTGACAAGCATTTAATTACCAACk(ACGCATATTCICACCiAAAGAATTATTCCG;ATGACAGGTGGG AAAGGAATTCT ATCITTCATTTTAATAGS'ITGGATCTATGATGTCTAhTTGCAGGTGOAATTTATATTTGS-PA AGA TATAAGALAATCT-AG TGATA TAT CTAGAGAALkAGA JTA A 10 0?? amino acid see t SEQ H) NO- 202)k D,!RXYQRSXI LTLSLFCLSQI PLN,,TNVLGESTVPENGAGI-KLV-T-VKKTDDQNKPL-SK-ATFLRTT AN 2551<3 RV'TAELTGEATF'DNL IPGDYTLSEETA PEGYKKTNQWQVKVESNG STT 3.QN4SGDKNSTIGQN QEELDKQY P PTGIYEDTKESYELERVK GSVPNT JKSEAN AV N PYS SEGER- I RETI PEGTLS KRX SEVGDLAHNKYKIELTVSC KT IVKPVDKQKPLDVVFThDNSNSMNNDG PNFQRHNSA?%KKAIAEALGTA'VKDI LO ANSDNRVALVTYGSDI SD Is GRSVDW, KGFKEDDKY GIQTSFT IQTENYSH} QLTNNAEETI I RIPTEAIS ASNGSTT IT PEQQ} .EYYL SS'VGETFT ISAFMEADDI LSQVNRNSQS I IVN VTDiGVPTRSYAI NNFSLaASYESQFEQMSSNGYLINSSNFrL LTDSPEDI SGNGESYFLFLDSYQTQ1IISGNLQSLRYLDLNLNYPSGTFYRN-GPVRE-GTPTSLY INS LSQS NYDI SNEG IDI SGFRQV)'YNEDYSS. QDGTFQSLSEEAFELSDGE ITELMSSFSSEPEYYTP IVTSSDASNNE ILSSIQQQFEILTENSIVGTIEDPGDINLQGNGTLQKDYTLQGNDGSTMKDSIATGGPNNDGGI 20 LSGVS 7LEY I NSLYV RGLNLGEGQK-VTLTYPVSLDDSFI SNSB'YDTNGRTTLNFSSEDPNTLRDFP 3.2515 VI4 EY?T IT I EKSOEI EFT SVDKDNNSLLLKOATFELQEFNEDYSLYLPI SNNIBKVV-TGENORI SYSOL SGYQLIEAVSPKDYQSITNSPILTW-EVVSG SIQNIIA.1VNSQIS-EifEEODSHLITNITHIPPSGI IPXTGG SGILSFILIGGSMMS1AGGIYIWSRYSSSSDISREKD 25 Strain lC458 ORB'E DNA sequlence (SEQ 1D NO:0 222) 2 -GAGAAAA- TA CC. AlAATTTTC-TAAAPATATTGA-CTT-'ACGTCT TTTTTGTTTGTCCAA TAC~CGCTTAT AC0~ATGTTTTAGGG0AAAGTACGTAOGGAAA-TGGTGCTAA GGA.AGTTAGTTGTT.AAAAGACAvAT G'AC-CAGA.PACAAACCACT.'TTCAA.AAGCTAO-CTTTGTTTTAAtIAAACTACTGOTCA'ITCCAGAAAIGTAAA. kTAGAA 30 AA;AGTMACTGCTG3AGGTAACAG;GTGA.AGCTACT TTGCATALATC?CA.CACkCTGGYAGATTA.CACTT-TATCAG7AA O-A.7AGGCACCCG.AAGGrATP~AAAAAA.GACTAO-CC-AGzACTTGGCAAGTT-AGG.TTGAG,-AO TAATGGAAZAAAT-T ACGATACAAAATAGTGATGrAT.AAAAAATCTAThATTGAACAA AGGOAAGA-GAA CTAGATAAGCAGTATCCC CTTACAGGAGCTTATGA%GATACAAAkAATCTTkTAATCTTG AGCATGTTAAAAJTCAA TTCCAAA TOGGG AAATTAGAGIGCAAA2 AGCAG TTAATCCAT~ATTCAATGAAGGTGA2CACATAAGAGAA2%ATT-AAGAOSGAACA 35 TTATCTnP.CGTATTTCAGzGTA4TGATTGGATCTATAA!ATATt4A -TTGAGTTPCTTTO -COG"T AAATC-CATAATAAAAACTATAAF ATAAAGATGAACz ,CTCT GOATGT-TGTTTTTGTTCT-TGATAATTCAAA TTCT ATC-GAAAA,TGGAAAAA ,CAGCAX AAGGCDGCTGAGCAGTAGAPJ\ACAA TTATAAA, AATGTT TTAGGAGCAAAkTGTTGrAAA COGAGCAGCTTTAOTTACTTATGGTTCAGATATTTTTG'TGGAAGCAGAGTT .A; AGTTATAAAAGGjTTTTA.-AGAGGATCCTTATCA TG ACTTCAAACTAnGTT TC.ACAGTTCAGAOA'21AATGAT 40 TATAGOTATA AAA'AGTTCACTA-ATATT'GCTGCTG,'ATATTATP.A-AAAGATCCTAAPCAGAGCTCCAGAAGi.CCT AAGTGGGGGGGGACAAGTCTAGGATTAACTOCAGAAAA1AAGA.GGGAATATGATTTA-AGTAAAGTAGGTGAG AOL CTTTACAATGA.A GCTTTTATGGAGGOAGATACCTTGTTAAfGTAGrTATACAGCTAGAGTAGAAAGATT ATTGTTCATCTAACTG5AOGGTGTTCOAAOAAGkATCATATGCTATTAkATAG TTTTGTAACAGGTTCAACATAC GCAAATCAATTTGAGrAGAATAAAAG2%AAAGGTTATTTAGA'4CAAAAATAATT.ATTTTAkTAACTGATGATCCA 45 GPkAAGWA.A.AGGCAAkTGCG GAATTACTTTTTGTTTCCCTTAGA TAGTTATCAAAO 'ACAGA TAATTTC T GG AAACTTAC AAAAACTTCATT-ATTT AGATTTAA.TCLTA.ATTACCOTAAAGGTA ,CA1\.TTTATAkGAA-XGQALi CCAGTAAGAG AACAzTGGAACA-COAACCAAACTTTATATAPAATAGTTTA4AAOAG-A-AAATTATGACATC TTT AATTTTGGTATAGATATLATCTGGTLT'-TAGACAAGTTTATAA3 TGAGG3ATTATAAG AAAAkATCAAGATG GTAC:T TTTCAAAA;LATTGPAAGAGGrAAGCTTTTG AAOTITTCAGGTGOGGAAATAA7 CAGAACTAAkTG-AAG TCATTO TOI.T 5 0 TCTAA.COTGAGTA;TTATAOCCOOA.2TAGTACTCAOCTGA-TGTATCTA TAATGAAATTTTAiTCTAAAsATT CAGCAACAATTTOAkAAAGATTTTAACAAAGG-3AACZTCAATTGTTAA TGGAACTAT.RGA.AGAT.CCTZTGGT GATAAiAATCAA' TTTACrAGC1'TGGCAACGGACAAAC-ATTGO-AAOZCAAGiTGATTATACTTTACAGGGAAATGAT TTAGAA71TACATCAA2%AAAT, AAOCTACGTTAzGAOGTTTGAA %CTTAGOGGAGGGGCA.AAAAGTAACACTCACA. 55 TATGATGTGAAA ICTAGAkTGACA-GTTTTATTAO-TAACJuIATTC'TATGA CATAATGGTAAACAAC-ATTO-AAT GCTAAATCAGA OGANJCTG.ATACACTTAGAGA TITTOCCAATCCCTAA.AATTOGYTGAPTGTG AGA7GAATATCCT ACAA TAAO-GATTA.AAP7 ACGA.GA.AAAGTTAGGTGAA&,TGA.tTTTACAAAA2 GTTG ATAA,1AGATAATA.ATAA %G TT($CTTCTC7-AAGGAGGCTACATTTGAACTTCAAGA ATTTAATGAAzGATTATAAA-CT TTATTTACCAATA~AA AATAATAAT TCAATS.TGACGGGAGA.AAGGCAA%-ATTTTTAAAA~jGATTT-AAOATGOCAAAiTA'T 60) OAGTTAATAGAAGCZGTTTCGCCC-AAG-GATTATCAAtAAAATTACTAAZTAAACCAA-TTTAACT.TTGAArTT - 125 G-TT.AAAGGACAAATTATGTTATAGATATTCTGAATAT CTGAGGAAGTGACAAG CATTTAATTA-CAA-ACGCATATT-CAC-AA AG,ATT-AT TCCOATGACAG GTGGG AAAGG.ATTCT ATCT TTCATTITASATA GGTGGAGCCTATGATGTQ-TATT-GCAG GTGGAAiTTTATAT TTTGCAAPIA.tACATAACAAA-TCT AG'-TGA.TGCATCAATCGAG AIAC.ATTA.A 5 ORF amino acid saouence (SEQ JOD NO: 203) KVTAEVTOEATFDNIJT GDYTLSEETAPEGYKKTTQTWQVKVE~,'FSN GKTT JQNSDDKKS II EQRQEELDKQY P LTGAtYEDTKESYNLEHVKNSS PNGKLEAKAVJ7PYSSEGE4I RE QEOTLS RI SEVrNDLDLNIKKI ELTVSG KS 1 T INEDE PPVWEVVLPNSNSMKtNGKNNRAFKAGEA4VET ITKDVJLGANiVE? RAALV.TYGSDI FDCRPTV .0 CCVI KGFKEDPYN:GLETSFTVJQTNDYSYKKFTNIAAkDI I 10(1KEAFEAKWGCTSLCLTPEKKREYDLSKVJGE TFTNvKAFMEADTLLSSIQRKSP.KIIVNL.TDOVPTRSYATINSI-VTGSTYANQFERIKEKGYLDKNWYFZ TDDP EKIKONGESYFLF-PLDSYQTQI ISGNLQKLXYLDLNLNYFKGTI YR NGPVR(EHGTPTKLY INSLKQKNYDI F WEGI DI SGFRQVYNEDYKKNQDGTFQKL KEEAFELSGGE ITEL IKSFSSKPEYYT PIVTSADV SNN I LSRI QQQFrEKI LThENS INOT IEDPMGicDKINLOLGNGOTLOQPS DYTLQGHOGS IMEDS IATGGPNNDGGI LEOTSI 15 LEY I KNRKLYV~RLN LGEGQKV' TLTYDVKLDDSFI SNKFYDTN-GRTTLNPK'SEEPDTLRDFP'I SKI RDVEYP TI TI KNSKKLISEFTKVDKDUNaKL1.tKGATFEILQEFNEDYKbYLP IKNNNSKVVTGENGKT SYKOLFOOKY QLIEAVISPKDYQKITNKPlLTFE\, IKGSIQNI IAVE'NKQISEYRiEEQDKN-LITNTHNIPPKGVIIPMTOGKQILS FI L1-GAMN.S IA'G! YIWKKHKKSSDA'S ISKD 20 Table 12: Amino acid and encoding DNA sequences of gbsZI0l8 proteins derived from different strains of S. agakwctiae Strain OIIGH4A ORF DNA seguence (SEQ ITD NO: 10); 25 ATGAATAATi.AGGAAAAAAAAk.GTAAATACTTTTT-AO%.k. UAAAGOTTATGOTTTOG(CCTCAATGT.CAGO:A GCGTTTGCTGTATGTAGTGGTATTGTACAOOCGGATA CTAGTTCAGGAATTAT CGGATTCA ATTCCTCAT.AO AAkACAAG1,'TT.AATTTACGGGGG-GTTAC 4 !''-GnAG'AATTTGATTXTCTA,AATCGTGQ-TATGACAA*,CTATT GCTATAC'TTCTAAGT AGAG TAGATGA-"TTTAATAGAGCATCAC-AGGA TACACTTCCACAATTAATTAATAGT AOTG AA GCAGAAkATTAACAATACTTTA(;CTGAGGGACG-AATTATTAAACAGAQGTATACCA3TOGTAkAGATTA 30 AAA2%GTTGAGAGATTGGGAAGT JGTGCAAT TAAGOCTGAGTCGATTAATA11ATATTM'LATGCTG.AATCA4TTAUC AAVTTCAGGGTAAAiTCAAC'PTAITACAA.TTAAtGGCTGA'GT4CCAT4TAATMA-TT~AAGTAGAG TCTATTAAT ACAAPTTAAGGCTGAATCAATTCATAAAATTAAACCTCAAPTCAATAAAAADGTACTAGTGCTACACATGTTAAA GTTAGTG.AT CAI AAACTA(R'CTlAAGCAGTCAAGACGTTCTG)AGA'iTTC.ATTAAAI TCAZTTAGGTTTCGTI-TO-A 35 TCAGAC.AAAAAGATAT TTTAO TTAA,,ATCTATTAGCTCTTCAAIAGATTCGCAACT TAT TCT TAA1ATTTGTA ACAAGCCACCAACT2A.ATA.ATGCTGAATCAAX AAGCTAAGCACATGGCTCAA.AATGzACG(TGGCTITCA GTTGATGAGCTTGTAGCAGAIAGCTkZflAAGTTGTTAATTCAA-ZTAA GALACATTGGTAATCAGCCAAT GGTAA-6AAAGCAAG,-AAA TTGC-TAAPGTTAGAAAAl~TTTATCTAAC. GATGAAA TGTTGAGATATAAPTACTGCAkATT 40 GAT7ATGTAGTGAAACnGTAT- -TGAAGGTAGTCAATATTATATGCATG;ATGC:TTTAAAPTAGT-ATT AAG1VAAGCAGOA. CAGGAA GTT'GCCCAGAAAA1-ACTTACA iJAGCAGTATGCTAAA2-AAATTGAAASGATAAGT T TMVAG GAT TACGT TAT CUAAA ACGCTAAGAAA TT TAT GAAAAIGCAT.AAAGTAT T TT GC CTACACC T GGATATTATGCAG:-ACTCTGT0(3GAACTTATTT&IA~TAGGT-TTAGAGAT.kAACGAA;%CTTTCGGAADATAGAAGT GTTTGGAC-TGGTCAAZAGTG ACTTGATG AAGCAAAAMA -7-?TGCTTGATGAAGTCAMAA, 'GCTTTT2'AAAGAAz 45 CTTCAA IGACCTTA.CCAXAGGTA' ICTtZAAAAAGATAAAt'AAACCAGAOGTT AGCCAGAAGCCAA~iCC,GLGGCC A aACCA ATATTCAAiGTACCTAAA-CAAG CACCTA'CAGA.AGCTGCAAAACCAGCTTTGTCAPCCAGAAGCC-TTG , AGAT-,TkC'TG.I-,TCGCIALAACGTiVGG;TtAGTACGCV.- GA GATJATACTTGCAGT TCAAAAAGCTGTTGACCAAGCTTATGATCATGTGGAAGAGGGAAAA;LTTTATTACCACT GATAACAATAATAGTACAGCTACCTGATGCT TTACA.AAGTTTAGAAT TAAAGATjAAA-AGTA 50 GOCAS-.ACCAGAAGC TM GCCAGA;.AGTT.AAA71CCA2'.AGCCAA.ACCAGATGTVTAAGCCAGACGTTAAGCCAGA GCTAAG CAGAAGCCAZAACCAGzAGGCCAA; ACCAGAAG CCA.AACCAGATGGCC-AAACCAGAAGCCAr AACCAGAG GOTAAG CCAGAA ,GTT;-AAO.CAG ACGTTAAG7CCAGAG GCCAAACCAGA CGTTA.AGCCAGAAGCQA 1AACCAGAC GTTAAGCCAGAGGCTA'AGCCAGAA,'GTTAAA CCAGACG L-TAAGCCAGAAGS.TAAtICCAGAGGCTABAACCnA-A ATTAAAC^CAGACGTTAAGC'CAGA GGCCAGA;ECCAGvAC-GCTAAG CCAGAAGTTAAACCAGACGTTAAGCCAGAG i5 GCCAAA CCAGAAGTTACCAACGTTAGCCAGAGGCCAACCAGAGGCTAAGCCAGAiAGTTAAA CCAGAC G TTAAGC AGAG GC TAA.CCAGAAGCrCrAAAO.CCAPC AATC CAIAAATCG G TTAAT ACTAG C GGA AAC TTGGC G GCTAAA,-JGTATTGAAAuCPJLAAAGTATAGT~~AAAAAATCCATCAACGGGTA3'GCGCAG.rTCGAOTC -126 T TAGQC T GTATCACTATTAGTTAGAC-TGCAGTCTTAT TAQSATAGTTTT2A,'-TAIAAAV 2iAT TAA ORF amino acid sequence (SEQ ID NO: 175); MN UNEKK 'K'LRF: AYGLA3MSAAFAVFCSGZ-VHADTSSG I SDS I PHPKCVN4LGAVTLENL I SKYRGNDKAI. 5 AlILLSPAT DDFN4RA. SQDTLFQLINSTEAE1NNT LPQGRI KSPVLKELSAKESN4KEI

KIQGKSTN

m IKA6ESI DNKIK/E SlINTIFAES INKITQAKPlNTI KAES INTIKAE S I KIKFPQS IKST SAT{VK VSDQEL;AKQSFPRSQDI I KSLGFLSSDQEDI LV1V3 I SSSKDSQLI LKFVITQATQLNNAESTKAKHMA QNDV AS I KNI SLEVLEEYKEKIQRASTKSQVDELVAEAKKVVN %SNRETLNTQANGKKQE IAKLENLSNDS-:MLRYNTAI DUeV7QYNEQKLNT TPDANNALIS I KQAAQEVA'QKNLQKQYAKK 1 RI SLEGLALSK . AKEI YE: 1K3 1L2T P 10 GYYADSV GT YLNRFRDKRTFGNRSVN 'TGQSGLDEAYKMLDEVKKLLKELQDLTRGTKEDKNPDVREAPEA RKPHIQVPRQA PTEA PALS PEA LTRLCTNY NQAKDLLKDDQsVKDKY VD1 LAVVQFrAVDAYDRVEEGKFI WY DQANQLANRLRDALQSLE LKDKKVAK PEAkKPEVKPEAKPDVKPDV KPEAY, PEAI 25A PEAK PEAK PEARPE ARKPEVKPDVK PEAK PDVKFPEAKPDVE PEAK PEVK PDVKPEVKPEAK PEI IX PDVKPEAR PEAK PEVK PLO/E AKPEVKPD)VRPEA :PEAKPEVPW PVPEAR PEAKPA.TKK3VNT SGN LAAKK.A T .1 / R2TE PL Is LAIVSLlVMqLSAGLITIVLKl1KKN Strain 12401 ORE DNA requlence (SEQ ID NO: 13i): ATGArATAAT -AACG AAAA.AAAAGTAAAATACT m TTTAAGA AA.ACAGCTTA LGGTTTGG'CTCAATGT-CAGCA 20 GCGTTTGCTGT ATGTAGIGGTATTGTACACIGCCGATACTAGTTCAGGAATATCIGGA TCAATTCCTCAT AAG A.AACAAG.vTTAATTTAGGGVGCGG TTACTCTQAAGAATTTG-ATTTCTA.AATATCG:TGGTATATGAC-AAA GCTIATT GGCTATACTT TT-rDGTAGAG TA.T-GA.TTTT;ATAGACSJ !CACAGG:ATACACTTC-CACAAT'-TAA 4TTAAT-AG,-T ACrTGAAGCAGA AATTA., AATACTTTAC-CTCAfGGACGAATTATTAAC '..AA(TATACCArGTCGT AACA.lTA AAAtGTTGAGAGAT'I'GGG^AGTGGTGCAATTAAG GCTGAGTCGATTAATAATATTAAt AGCTGAATCAATTAAT 25 AA1UATTCAGGGTAMC ACAAC4-TAATACAATTAAG GCTGAGTCCATTA.ATAA-rAATTAAA 5GTAGAGTCTATTAAT A CAATCAAAGCCGAAPTCAATTAASTAAAt ATTCAAGCT.2AGCCAATTAACACAATCAAAGCCGAGTCTATWAe'AT A'iCAATTAAGGCTGAATCAA, TTCATAAATTKAA7CCTCAATCP ATAAAA Ai LTAC^TAGTGCTACACATCTTAAL GTTAGTGATCAkAG, %ACTAGGTAAGCAGTCAAGACG TTCTCAAGATATCATT %AATCATTAGGTTTCCTTTCA. TCAGACC.TAAAAGATATTTTAYTIATCTATACCTCTTCAAAAGATTCCAACTTATTCTTAATTTGTA. .30 ACACAAGCCACGGAACTGAATAzATCCTGAATCAAC 1AAAGCTAAGCACATGGC TCAA.AATGACGTGGCTTCA A'TAPAAATATAAGCCTC GA'AGTCTTAG.AAATAT~AAGA.AAAATTCAAGCTAGCACTAAGzAGTCA GTTGATGoAGCTTGTAGCAG7AAGCTAAA.iAAATTGTTAIATTCCAATAAAC-AAACATTGGT;AATCAGGCCAAT GGTAIA,AGCAACAA,-ATTGCTAAGTTAG'-AAATTTATCTAA %CGATGAAATGTTGAGATATAATA CTGCAkATT SATAAPTGTAGoTGAACAGTATAATGAAG GTAAG CTCAATATTAzCTGATGCAATGAATGCTTTAAlATAG TATT 35 AAGCAAGCAG,-CACA GC-~ATTGCCCACAAAA ,ACTTACAAA,-AGCAG TA TGCTAAA. -VnATTGAAGAATAAZT TTAAAAG GATTAG CGTTATCCAA"AAAGGCWIAWAAAzTTTATGAA.,AGCATAAA AGTATTT TGCCTACAC CT GGATATTATGCAGACW-'!CTGTGGAAJCTTATT TGPA'TAG3GTT TAGAGfAAACGiVACT TTCGGAAATAGPAGT GTTTGGACTGGTCAAkAGTGCAC-TTGATG'A.AGCA-AAA'AAATGCTTGAT3AA.GTCAAAArA'iGCT TTAAAGAA. CTTC-;AGACCTTACCAGAz'GGTA CT;AAAGAA GATAA-AAAA CCAGACGTTAAGCCAGAAGCCAAACCAGAGGCC 40 AAACCPJIATA TTCAAC TAC CT AAA CAAG CnC CTA CA GAA CCT GCACAGC T T TGTC ACAGAAGC CT TG A^CAAGATTGACTACA TGGTATAAPTCAA24GCTAAGATCTGCTTAAAGATGATCAAGTA.AlAGGACAATATGTrA CATATACTTCCTTCAAAAAJGCTGTTGACCAA zGCTTATGATCATGTGGAA JGAGGGAAA!ATTTATTAC-CACT GATCA-PACAAATCAATTAGCTAAC-AAGC'-TACGTG ATG-CTTTACAAAG(TTTAGAAkTTAAnAG ,A-tAAAAAAGTAr~z SCCAAACCAGAAGCTA~AGCCAGAAGTTAA ACCAGAAGCC-AAACCAGAGGCCA; AACCAGAAGCCAAA, CCAGAG 45 GCTAAGCCAGAA.GTTAAkACCAGACGTTAAGCCAGAGGC .AACCAGACGTTAAGiCCAGAAGCCAA.-ACAC NTTA-AGCCAGAAG~rTTAAACCAGACGT TAAGCCAGAGGCCAAACCAGACGTT.ACCAGAAGCTAAG CCAGAC GTTAAGCCAGAGTT~sAACAGvAGGCTAAG."CCAGAAGCCAAAIlCCAG AGGCTAAAICCAGAAATTAAAC CAC GTTzAGC-CAC AGGCCAGACCAGAGGCTAA74GCCAG-AAGTTAA,'ACCAGACGTTAAGCCAGttGGCCA AACCAkGAG CTTAAGCCAG7AAGTTAA' ACCAGAC GTTAAGCCAGAGGCTA.AACCAGAAU200AAACCAGCAPACCAAAAAA7TCG 50 GT KAATACTAGCGGAAACTT GGCGGTTAAz-AGCTATTGAA.AAGTATAGTAAAAkATTACSCATCA CCGGGTGAPAGCCGCAAGTCCATCTTAGCATTGTATCACTAATTGTTATGTTAAGTGCAGGTCTTATTACG A TAG TT TTAAAGC ATI-AAAAAAT TAAk ODU amino acid sequence (SEC I12 11C 176). MNNNIEYKKVYFLRKITAYGLSN SAAFAVCSGIVNADTSSGISD)S IPHKQVN l-GAVTLKFNLI SiYRGNDK~l 55 Al LLS RVN DENRASQDTL PQLI11NSTEAS I NNTL PQGRI I11023I PVVRLKVE RLGSGAI KAES INN I KY S IN KIQGRSTNTIKAESINKIKV-,ESINTIEAESINK QAKPINTIKAESNTIRAESNKIPSIKTSATVK VS DQELGKQSRRSQDI IKSLGFLSSDQKDI AES I SSSKDSQLI LKF-VTQATQ-LNNAESTYKHMAQNDIVAS I KU!SLSVLEEYKEKI QRASTESQVDELVAEAKKVVII SNKETLVN-QANGKKQE IARLEULSUOLL LRYNTAI DNVr VKQYNEGKLNITDP.kINALNSIKQAAQEVnCRNLQKQYAKKIERISLKGLALSI<RAKEIYEKRKSIPTP 60 GYYADSVGTYANRRRDKRTFG NESVWITG-QSGLDEAKMLDEVKKLI2 ELQDLTRIGTKSDKKPCVERPEARPEA -12'7 F KPN IQVPKQAPTEAAK,,PALS PEALaTRLT TWYNQAFDLLKDDQVKDRYV I~ LAVQKAVDQnYDHV VZEGKFI TT DQANQLNLRDLQSLELDKVAJAKKPEVFEKU FEAKFEAKEAPEVKPDVKEAPDV/KPEAN2D FVKPEVKPDV KPEAKPIDVKPEAKPDVK7PEVKPEAKPEAKPEAK2E IKPDVIKPEA RFEAKPEVKFDVjKPEARFE Strain BAA23 OR DN ejence (SEQ ID NO: 182): A.TGAA-PTAATAACGZAAAUAAATAAATATi TTAAGAAAA-ACA2-CTTATGGT TTGQCC,-TcAATOTC.Ac-A 10 GCGTTTGCTGTATGTAGTGGTATTGTACACGCCGATACTAGTTCACGAATATCCCATTCAA.TTCCTCATAAG AAkCAAGTTAATT'SAGGGGCGGTTACTCTGtGATTTATTTCTATTCGTGTA,;TGC.AVGCTATT GCTATACTTCTttAGTAGAGTAGATGATTTTAATAGAOCATCACAGGATACACTTCCACAATTAAkTTAATAGT, ACrTGAAAGf'AAATTAACAATACT'TTACCTCAGzGGACGAAlsTTATTAAI ACACAGTATACCAGTCGTAAGAT TA .AAOTTGAGAGATTGGGAAGTGGTGC.AATTAAG7GCTG7AGTCGATTAATA.ATATTAAG.CCTG7AATCATA 15 AAAAT TCAOGGTAAA2%TCAACTAATACAATTAAGGC'TGAOCTCCATTAATAAAATTAAAsGTAOAGTC TATTAAT A CAA TC-AA C CGAATC AA T TAA TAAAAT T CAAG CTAA'CC CAA TT AA CACAA T CAAAkGCC GAG T CTAT TAA T ACA;ATTAkAGGCTOA.ATCAATTC'ATA? -AATTAAA,%CCTCA;ATCAATAAAAALGTACTAGTGCTACACATOT TAA GTTAGTGATCAA, GAAkCTAGCTAAGCAGTC~zAGACGTTCTCAAGATATCAT TAAATCATTAGGTTTCCTTTICA T CACACGAOV~AATAT-TTAG TTAAT C TATTAGCT CT TCAAAGAT TCC AACTTAT TCTARATT TGTA 20 ACACAAGCCACGCA-ACTOAATAATGCTGAA TCIACAAAAT-GCTA.AOCACATGOCTCAA7 AATOAC GTGOCTT-CA ATAQ'AAAATATAAC CT CGAAGT C TTAGAAGAATATAA AGAAAA?,AAT TCAAACAGC TAGCAC TAAGAG TCAA; CGTAAAMkGCMAG.' AMTTGCTAtiGTTAGA.AAATTTATCTAACGATGAAATGTTGAGATATAATAC-TCCA-ATT G2ATAA7 TGTAOGTGAAAkCAGTATAATG-AAGGTAACCTCAATA TTACTOATGCAAZTGAT ATGCTTTAA-ATAGTATT 25 AAGCAAGCAGCACAGGtAOCTTG-CCAA.LACTTACAA&AAGCAGTATOCTA.AAAA %ATTAAkAGAj~ATAAO;T TTAAAAOjGATTAGCOzTTATCCAAAAAIGCTAA AGAA;ATTTATGAA7 AAGCATAAAAGTATITTGCCTACACCT GG ATATTATGCAGACTCTGTOGGAACTTATTTGAATAGGTTTAAGATAACG,CTTTCCGAAATAGAAGT (3TTTOGACTQGTCAkAAGTGCACTTGATGA.ACCAAJAAAA; UTGCTTGA3%TGZIAGTCAAAAuAAGCTTTTAA-AGCAA4 CTTC?.AGACCTTACCAG AGGTATAAAGAAATA22,-A-AGACTTA CCCAAGCCA'ACA ,AG X 30 -AACCAA ATATTCA.AGTAC-CTAAACAAGCA.CCTACAGAGCTGCAPAAGCAGCTTTOTCACCAGAAGCCTTG ACAlAGATTGAC-TACATG GTATAATC AAGCTAACATCTGCT 'TAAAGAr TGA'TCA AGTAAAGGCAA ATATGTA C3ATATA TT T GCGT T CTAPGC T G T TGACCA AGCT TATAT CATG TGGAGGGAAAET TAYTAC CAC T GATCAAGCAAATCAkATTAkGCTAACAAGATACGTCA7GCCTTACAM, GTTTAGAACt.TMP AAGATAM AACt.TA CC-CAA24ACC.AGACCCTA'4AGCCAGAAZGT TAAACCAOACOT TAGCCAGAOGCCAA ACCAGACGTT.ACCACAA 35 GCCPLAA CCAGACG"TTACCCACAACTTAAAlCCAOGACCTTMC.CCAACGCCAA ACCAGACGTTAAG CCAO,A CCTAAGCCAGACGTTAAGCCAGAGTTAAACCAAGGCTAACCAGAGTAAACCAGACGTTA.AGCCAGAG CCCAGAC CAGAGGC TAAGC CAGAAG TTAAAC CAGAC G T TAG CCAGA GGC CWACCAGA.GC TAAGC CAGAA GTTAA %ACC"AGACGTTAAGOCACAGCCTAAkACCACtAGCCAACCAGCACCAA~ztAAATCGGTTAATACWAGC COAAAC TTGGC-GGTTAAAAAA, GC-TATTG.A~zAAAAAAGTATAGTAAAAAATTACrCATCAACGGGTGAC .hC 40 CCAAGTCCACTCWTACAATTTATCACTAATTGTWATGTTAAGTGCnGGTCTTATTkC'GATAGTTTTAAAG CATAA&X-MATTAA ORE' a.. mo acid se:O uence V'EFQ ID NO: 177) . I-.NNNEKgVKYFLRKTAYGLA;,SMSAAFAVICSG7IVI-ADTSSGI SDSI 2HKKQVZTNL(3AV'TLRWL 1 KYRGNDRA-I AILLSRV ,DDFNRASQDTLPQIJINSTEAEI-NNTL-PQORII<QSIF VRL-KVJERLCSGAXRAESI-NIKAES1N 45 KIQGNSTNTXkESNKVESINTiESINKQAX2KINTIKAIESINTIKA ESIHKIKP:QSIZ -,STSAT4HVK VSDQELARQSRRSDI IKSLGFLSSDQKDlLVKSISSDQIKVT Q-NA~TAHAFDA I KNI SLEVLESYKEEIQRASTKSQVDELVJAE.KKVVN,' SNRETLVNIQANGRKQE IAKLENDSNDENLRYNTAI D.TNVEQYUEGKLNI TDAMN4ALNS IKQAAQEVA ) QKNLQKQYAkKIERI SL (SLALSEKA KE iYEKts I LpT p GYYADSV ,GTYLNRFRDERTR NRS'V 'ITOQSGLDEAXKNLDEVI<NLLEELQDLTRGTKEPKKPDVE 7FPEAKPEA 50 KPtIIQVPNQAPTEAAKPAISEALTRTTVYNQAKDLLKDDQVKDKYVDI FAVOKAVDOA YDHVEEG,7FI T DQAMNQLANK I RDALQSLELKDKhK ?FPEGEPEKPFDEIPAPVKPER.PR)'rPEVKPDKPAKPDVKPE AK PDVKPEVKPEAiKPENK PDVK PEARPEAKPEVKPDVK PEAK PEAK PEVKFDVK PEAK PEAK PATKKSvNT S GNILAVKnI ENKKYSRKLPSTG'rEAASPILAIVSL!VNLLSAG2L1T4IVKHiKN 5> Strain IG1O5 ORE' DNA sequence (SEQ ID NO: 183) ATGAATAATAACGA .AAAAA AGTAAALATACTTTTAAGA-AAAACAGCTTATGGTTT",GC-CTCAATGTCAISGCA, CTTTGCTGTA'IGTA3TCGT'AT TFTACACCGCA~' TACTACTTCAGCAATATCGGATTCA2ATTCCTCATAAG -AACAAGTTAATWTAGGGGCCGTTACT.CTOAAATTTG?.TTTCTAAA TATCOTGGTAAiTGACAAAGC2ATT 60 GOTATACTTCTAAGTAGA2,GTAG ATG ATTT TAATAGA GCATCACAGGAT.ACACTTCCACAA7,TTnATTA %TAGT -128 ACTGAAGzCAGAAkATTAkACAAJA' CTTTAC.CTCAGGGAC-GALATTATTAAkACA GAGTAT ACCAGTC'GTAAGATTA A 2AGTTGAGAGATTGGGAAG TGGTGCAATTAAGGC TGAGTCGATTAATAATATTA-AAGC TGAMTCMAT TART ?AAAATTCAGGGTAATCAAVCTATACATTA GGCT^;AGTCCATTA ATAvAATTAAGTAGAGTCTATTAA %T ACAATCA2AAGCCGAATCAAT TA4ATAAAATTCAAGC TAAGCCAATTAACACAATCAAA7-GCCGAG TC TATTMAT 5 ACAATTAAkGGQ^TGAATC3ATTCAT AATTAAACCT4AATCAATAAAAGTACTAGTGCTAC.ACATGTTAAAj GTTAGT ZATCAGAA&I .CAGGTAIIAGCAGTCA.AGAC-GTTCTCAIAGATrATCAWTA.AATCATTAGGTTTCCTTTCA TCAGAC 'A,-PAAAAGATATTTTAGTTAAATCTATTIAGCTCTTCAAAAGATTCGCAACT TATTCTTAAATTTGTA ACAAACCCGAATGATYTCTAAC2ACAGThAGCA-)CATGGTCTCAA,%TGAClGTGGC TT CA AT.AA.AAATATAAGCCTCGAAGT CTTAGAAGAATATA.AAGAAAIAAATTCA.AAGAGCTAGOAG TAAGAGTCAA 10 GT TrgA-TGAGCT TGTAGCAGAGCT.,P.V--AGTTGTTT TCAAAGAA- iACATTGGTAAATCAGGCC PAT GGTAA-AACCAAGA"AATTOCTAAGTTAGAAAAT-TTATOiTAAOCGATGAAATGTTGAGATATAATI'TGCAATT GA TA.ATGTAGTGAACICA2TATAATGAGGrTAAGCT-AATATTACTGATGCAAT2AATGCvTTTAAATAGTATT AAGCAAGCAGO-ACAGGAAGTTGCCCAGAAAACTTAOCAAAAGCAGTATGTAAktJX.AAATTGAAAYAATAAGT TTA ,AAAGGATTAGCGTTATCCA.AAAGGCTAkAAGAAPATTTATGAAAAGCATAAAAPGTA.TTTTGCCTA.CACCT iS5 GGATATTATGCAG ACTCTGTGGGCtAIQTTATTTGAA-TAGGTTTAGAG .rATAAACGAACTTTCGcAAA TAGAAG7T GTTTGGAOTGGTC'AA-AGTGGACTTGATGnAGACA.2-AAAAAATGCTTGATGAAGTG.AAAGCTTT TAAAAGAA CTTCAAi GACCTTAC-CAGAGGTACTAAGAAGA.zTAAAzjAACA GACGTTAAGCCAGAAG C'AACCAGAGGC PAACOAAATATTCAVGACC T-AATCA;GCACCTACAGAAGCrTGCO1A(AACAGCTTTGTCACCAGAAG-CCTTG ACAAGAT TGAOCTACA TGG TATART CAAGOCTAAGATCT GCT TAAAkGA.TGA TCAA GT AAAG G ACAAATATG TA 20 GATATACTT(CAGT TCP'.%VGCTGTTGACCAGCTTTGATATGTGAAGAGGGA-'aAATTTATTACC-ACT GATCAA GCAAZATCAATTAGCTAACAAGCTACGTGATOCTTTAC'AAGTTT-GAATTAAAi-GATAA.iAAGTA GCCAAA4CCAGAAG.CTAAG.CCAG.AAGTTAAACCAOAAGCCAAZACCAGATGTTAAGCCAGACGTTAAGCAGAA GCTAAzGCCAGAiAGCCAAAkCCAG2AGGCGA,.ACCA2AAGCCAAPACCAGA.GGOCA.AACCAGACAGPCQACPAACCACGAG GCTAAGCCAGAA6GTWAA4ACCAACrGTT?4AGCOAGAGGCCAAA COAGACT TAA GCCA.CAAGCA.AACCY GAG 25 GTTAAGGCAGAGGCTAAIPGOCAG~aAGTTAAA:ECCAGACGTTAAGGAGAGCCAA4CCAG ACGTTAAGCCGC A. GGTAAGCCAGACGTTAAGOGCAGALAGTTAA ACCAG AGGCTA.AGCAGAAGTTA.AACCAGACGTTAA ,GCCArGAG GCC-AGACCAGAGGGT.UnGr-CAGAAGTTAAAGCAGACGTTA-G,'CCA-AGGCZJCA.ACGAGAGG CTAAGCGAGAA, G'TTAAAPCCAGACGQTTAAGCrCAG AGGCTAt-AAAAAGOTAAA -CCAGCAA CAA-AAATOGGTTA.ATACTAGGC GG AAACTTGGCGGTTAAAA AGCTATTGAkAn fAA.AAGTATAGTAgJLATTCCATAACGGGTGAGCC 30 GCAAGTCCACTCTTAGC-AATTGTATCACTAA%-TTGTTATGTTAA"GTGCAGGTGTTAsTTA CGATAGTTTTAAA'G CATAAAAAAAATTA QEF amiCno ac ,5 se~.lEic (Eq CD 0: 1-72) Al LLSRV,%DDFNRASOTLE'QLINSTEAE I NNTLFPQGRI IRQSI1PVVRL-KVERLGSG AIRAES INNS. AE SIN 35 KlQGKSTNTlKAESbKIVEaITNTIKAESINKIQAPINTIAESINTISIKIKQSIKSTSATIH K IKNI SLSVLEEYKEKIQRASTKSQVDELVAEAEK,, VV14SNKSTLWINQAWOKKQE IA} LENLSNDEMLRYNTAI DNVVKQYNEGKLNITDANNALNS1KQAAzQEVAQKNLQKQYAKKERISLKGILALSKKAKEIYEKHKSILFP GYYADSVGTYLNRFRDKRTFGNS.WTGQSGLDEAKKML"DEVKKLLKELQDLTRGTKEDKKPDVKEAkKPEA 40 KPNIQVPKQAPTEAAKPALSPEALTRLTTWYNAKD-LKDDQVVKDKYVDILAVOKAV DQ2AYDNVEEGKFITT DOANQLANKLRDALQS LELKDKVAK PEA{PEV EA PDK PDVKPEAPEAKEAKPEAKPEAKPEAK2EPu AKPEVKPDV KFEAKPDVKPEAKFD 'KPEnKFEVKPDVKPEAKPDVKPEAE'DV7KEV"KPEAKPEVKPDV"KE ARPEAKPEVKPDVKPEAKPEAKPEVKPDVKPEAK2EAKPATKKSV;NTSGNLAkVRKAIENKRYSK KLPSTGEA ASF'ILAIVSLIV MLSAG'.L ITTIVLRRKKN 45 Strain 1C458 CEF .. DNA sequene (SE ID NO:. I84) A TGAATAATAACG AAA~AAXAGTAAATACTTTTTzVAGlAAAAACAGCTTATGGTTTGGCTCAsATGTCAGCAC GCGTTTCTGTAGIT~kGGGA .TA GA~TACTG TTCAGG AATC.GGC- UAzTTGCTCATI-C 50 AAkAC.,AGT T 1A'.TYAGGGCGGTTACTCT'-GAAqGAATTTGATTTCTAAATA-TCGTCGGTAATG AC-AAA-zGGTATT (3CTATACTTTTAAG TAOAGTAAA' TGAiTTTTAATTAGAtGCATCA'CAGGATAC,'ACTTCCA-CAA, TTA.ATTAAZTAST AICTGAAGCAGAAkATTA'PGAAATAT TTTATATCAAGGA71CAAAT GG-TAAG-CAAA,.ATAAACCA.AGTGTAAC..TAC-A CATGCTAAAGCTTAG.CTGATCAA-GAACPTAGGT-AGCAGTCAAGAC-GTT.CTCAA ,GAtTATC-ATTAAZGTCATTAG GT TTCCTTTGATCAG5ACGMAAkAGATATTTTAGTTAAATA.TATTAGCTCTTCAAAA; GATTCGCAACTTATTCTT 55 AA? T TTGTAA CTCAPAGCCACGCAACTGAATA ATGCTGA ATCAACA AAAG CTnAGCAAATGGCTCAAAATGAG GTGGCCTTA3%ATA.A-kCAATATAAGCCCCGAAG,-TCTTAG'AAGAATATA.AAAAAAATTCAAAl3%GAGCTAGCrAC T AAGAGzTCAAGTTGAT GAG TTGT AGCAGAAGGTAIAkA;AGTTGTTAATTCCATAAA GAAPACO-TTGGTA AAT CAGGCAAPTGG TAAAA2AGCAIAG 4 AATTGATAAGTT AGAAAATTTATCT2AMCG.ATGA.ATGT-TGAkGATAkTAAT ACTCACATTGATA'ITGTATGAAA4AAGTATA TGAGGJlAGCTCA-ATATTACTGCTGCAATGAATGCTTTA 60 AATAGT4ATTAAGCA AGC-AGCACAGGAAGTTGCCCAGAzAAMACTTACAAA GCAGTATGCT -A/.AAAA'TTGA -~ 129 ACAATAAGTTCAAAAGGATTAGCGTTATCTAAAAAGGCTAAAGAAATTTAT-AAAQCATAAVAGTATTTTG CCTACACCTGGATATTATGCAGACTCTGTGGGAACTTATTTGZJLTAGGTTTAGAGATAidMCAACTTTCGGA ATAGGAGTGTTTGGACTGGTCAPAGTGGACTTGATGAAGCAAPAAAAATGCTTGATGAAGTCAAAAAGCTT TTAAAGAACTTCAAGACCT TACCAGAGGTACTAAAGAAGATAJAACCOAGACGTTAAGCCAGAdAGCCAAA 5CAGAGGCCAAACAATATTCAAGTACCTAAACAAGCACCTACAGAAGCTGCAAAACCAGCTTTGTCACOA GAAGCCTTGACAAGATTGACTACATGGTATAATOCA-CTAAAGATCTGCTTAAAGATGATCAAGTAAAGGAC AAATACGTAGATATACTTGCAGTTCAAAAAGCTGTTGACCAAGCTTATGATCATGTGGAAGAGGGAAATTT ATTACCACTGATCAAGCAAATCAATTAGCTAACAAGCTACGTGATGCTTTACAAAGTTTAGAATTAAAAGAT AAAAAAGTAGCCA.ACCAGAAGCCAAACCAGAGGCCAAACCAGAAGCTAAGCCAGAAGCTAAGCAGAAGCT H0 AAGCCAGAAGCTAAGCAGAGGCC0AZ'AACAGAAGCTAAGCCAGACGTTAAGCCAGAAGCTAACCAGACGTT AAA0CAGAGGCTAAGCAGAAGCTAAACCAGAGGCTAAGTCAGAAGCTAAACCAGAGGTAAGCTAGAAGCT PAACOCAGAGGCAAACCAGOACAkAACATCGGTTAATACTAGCGGAAACTTGGCGGCTAAAAAGCTATT GAAA0ACAAVIGTATAGTAAPAATTACCATCAACGGGTGAAGCCGCAAGTCCACTCTTAGCAATTGTATCA CTAATTGTTATGT TAGTGCAGGTCTTATTACGATAGTTTTAAAGCATA'AfLfAATTAA 15 ORF amino acid sequence (SER I: ... 7). M~tm1ZJKYVFRTAY~leASNdAAAVCSG1 YHADSSG1SAS I PHKKQVNLGAVTLtNLI SKYRGNDKAI IAI LLSRVNDFNPASQDTLPQLINSTEAE IRN IL7YQGQiGQNKPSVTTRAKVSDQELGKQSRRSQDI IKSLG 20 NS IKQAAQCEVAQKNLQKQYAKKIERI SSKGLALSKKAKEIYEXHKSILPTPGYYADSVGTYLNRERDKQTFG NRSVWTGQSGLDEAKKMLDEVKKLLKELQDLTRGTKEDKKPDVKPEAKPEAKPNI QVPKQAPTEAAKPALSP EALTRLTTWYNQAKDLLKDDQVKDKYVDI LAVQKAVDQAYDHVEEGKFITTDQANQLANKLRDALQSLELKD KKVAKPEAKPEAKPEAKPEAKPEAKPEAKPEAKPEAKPDVRKPEAKPDVIKPEAKPEAKPEAKSEAKPEAKLEA KPEAKPATKKSVNTSGNLAAKKA I ENKKYSKKLPSTGEAAS PLLAIVSLIVMLSAGLITIVLKHKKN 25 Table 13 (A and B): Overview over the two runs of sequencing of the six antigens from various GBS strains; SEQ ID NOs of the corresponding proteins are listed. A Strain name Serotype gbs0233 gbs1087 gbs13O9 IC97(11 SEQ ID NO 235 nd. nd. 1C98 (11) SEQ ID NO: 236 SEQ ID NO: 287 SEQ ID NO: 317 105 (IV) IV SEQ ID NO: 59 SEQ ID NO: 71 SEQ ID NO: 83 IC108(III III SEQ ID NO: 237 SEQ ID NO: 288 nd. 10216 (Ib) Ib SEQ ID NO: 238 SEQ ID NO: 289 SEQ ID NO: 318 10244(1II) III SEQ ID NO: 239 n.d. SEQ ID NO: 319 IC245 (Ib) lb SEQ ID NO: 240 SEQ ID NO: 290 SEQ ID NO: 320 1C246(111) III SEQ ID NO: 241 SEQ ID NO: 291 n.d. 102 47 (111) 111 SEQ ID NO: 242 n.d. SEQ ID NO: 321 102 50 (Ib) Ib SEQ ID NO: 243 SEQ ID NO: 292 SEQ ID NO: 322 10251 (V) V SEQ ID NO: 244 nd. SEQ ID NO: 323 10252 (111) 111 SEQ ID NO: 245 SEQ ID NO: 293 SEQ ID NO: 324 1C25212 (III 111 nd. nd. nd. IC253 (111) 111 SEQ ID NO: 246 SEQ ID NO: 294 SEQ ID NO: 325 1C254 (11) 11 SEQ ID NO: 247 nd, nd. IC255(V) V SEQ ID NO: 248 SEQ ID NO: 295 SEQ ID NO: 326 1C287(V) V SEQ ID NO: 249 rtd. SEQ ID NO: 327 C288 (Ia) Ia SEQ ID NO: 250 n.d. SEQ ID NO: 328 !C289 (Ib) Ib SEQ ID NO: 251 SEQ ID NO: 296 SEQ ID NO: 329 1C290 (IIM III SEQ ID NO: 252 SEQ ID NO: 297 SEQ ID NO: 330 1C291 (V) V SEQ ID NO: 253 SEQ ID NO: 298 SEQ ID NO: 331 10304(V) V SEQ ID NO: 254 SEQ ID NO: 299 SEQ ID NO: 332 - 130 10305 (IT) I SEQ ID NO: 255 SEQ ID NO: 300 SEQ ID NO: 333 IC306 (ib) lb SEQ ID NO: 256 SEQ ID NO: 301 SEQ ID NO: 334 IC361(Ib lb SEQ ID NO. 257 SEQ ID NO. 302 SEQ ID NO 335 Ic363 (III) III SEQ ID NO: 258 n.d. SEQ ID NO: 336 IC364 (111) 111 SEQ ID NO: 259 SEQ ID NO: 303 SEQ ID NO: 337 10365 (Ia) la SEQ ID NO: 260 SEQ ID NO: 304 SEQ ID NO: 338 non Ic366 (n.t.) 4ypeab!e SEQ ID NO: 261 nd. SEQ ID NO: 339 Ic367 (11) 11 SEQ ID NO: 262 nd n.d. IC368 (Ia) la SEQ ID NO: 263 SEQ ID NO: 305 SEQ ID NO: 340 I 377 (V) V SEQ ID NO: 264 SEQ ID NO: 306 SEQ ID NO: 341 IC379 (Ib) lb SEQ ID NO: 265 SEQ ID NO: 307 SEQ ID NO: 342 IC432 (Ib) Ib SEQ ID NO: 266 n.d. SEQ ID NO: 343 IC434 (III) III SEQ ID NO: 267 SEQ ID NO: 308 n.d. IC455 (111) 111 SEQ ID NO: 268 n.d. SEQ ID NO: 344 IC457 (11) II SEQ ID NO: 269 SEQ ID NO: 309 SEQ ID NO: 345 IC458 (Ia) la SEQ ID NO: 60 SEQ ID NO: 72 SEQ ID NO: 84 I0459 (Ib) lb SEQ ID NO: 270 n.d. SEQ ID NO: 346 Ic460 (I1) 11 SEQ ID NO: 271 n.d. SEQ ID NO: 347 IC461 (Ib) lb SEQ ID NO: 272 SEQ ID NO: 310 SEQ 1D NO: 348 IC4 62 (11) || SEQ ID NO: 273 n.d. n.d. 10463 (Ib) lb SEQ ID NO: 274 n.d. SEQ ID NO: 349 IC4 69 (v) V SEQ ID NO: 275 SEQ ID NO: 311 SEQ ID NO: 350 IC470 (V) V SEQ ID NO: 276 n.d. nd. 12 6H4A (Ia) la SEQ ID NO: 277 n.d. SEQ ID NO: 351 509532 (Ib) lb SEQ ID NO: 278 nd. nd. 6313 )111) III SEQ ID NO: 279 SEQ D NO: 230 SEQ ID NO: 352 12351 (IV) IV SEQ ID NO: 280 n.d. SEQ ID NO: 353 NEM316, 12403(111) Ill SEQ ID NO: 229 n.d. SEQ ID NO: 231 12403/2(111) 111 SEQ ID NO: 281 n.d. SEQ ID NO: 354 12401 (Ib) lb SEQ ID NO: 56 SEQ ID NO: 68 SEQ ID NO: 80 COHI1 II) III SEQ ID NO: 58 SEQ ID NO: 70 SEQ ID NO: 82 BAA23 (v) V SEQ ID NO: 57 SEQ ID NO: 69 SEQ ID NO 81 017 6H4A(11) SEQ ID NO: 55 SEQ ID NO: 67 SEQ ID NO: 79 A909 (Ia/c) laic SEQ ID NO: 282 SEQ ID NO: 312 SEQ ID NO: 355 c388/90 (ia/c) Ia/c SEQ ID NO: 283 SEQ ID NO: 313 SEQ ID NO: 356 2AA22 (III) III SEQ ID NO: 284 SEQ ID NO: 314 SEQ ID NO: 357 2603V/R (V) V SEQ ID NO: 285 SEQ ID NO: 315 SEQ ID NO: 358 49447,() V SEQ ID NO: 286 SEQ ID NO: 316 SEQ ID NO: 359 BAA6 II(V) V n.d n.d. nd. B Strain name Serotype .gbs477 gTs1478 gbs2018 197 mI) Ill SEQ ID NO: 101 n.d. SEQ ID NO: 379 1098 (II) It SEQ ID NO: 102 SEQ ID NO: 187 SEQ ID NO: 380 10105 (IV) IV SEQ ID NO: 103 SEQ ID NO: 188 SEQ ID NO: 178 j10108(111) II1 n.d. SEQ ID NO 189 n.d - 131 C216 (Ib) lb SEQ ID NO: 104 SEQ ID NO: 190 SEQ ID NO: 381 C244 (I 11) 111 nd, SEQ ID NO: 191 SEQ ID NO: 382 1C245 (Ib) lb SEQ ID NO: 105 SEQ ID NO: 192 SEQ ID NO: 383 1C246 (I11I) 111 nd. SEQ ID NO: 193 n.d. !C247 (III) III nd. SEQ ID NO: 194 SEQ ID NO: 384 C250 (1b) lb SEQ ID NO: 106 SEQ ID NO: 195 SEQ ID NO: 385 C2 51 v V SEQ ID NO: 107 SEQ ID NO: 196 SEQ ID NO: 386 C252 (111) 111 SEQ ID NO: 108 n.d. SEQ ID NO: 387 1c252 /2 (111) 11SEQ ID NO: 360 n.d. nd. 1c253(111) 11 SEQ ID NO: 109 SEQ ID NO: 197 SEQ ID NO: 388 -C254(11) SEQ ID NO: 110 n.d. SEQ ID NO: 389 1C255(V) V SEQ ID NO: 111 nd. SEQ ID NO: 390 TC2867(V) V SEQ ID NO: 112 n.d. SEQ ID NO: 391 IC288(7) la n.d. nd nAd 10289 (Ib) lb SEQ ID NO: 113 SEQ ID NO: 198 SEQ ID NO: 392 10290(T11 I11 n.d. nd SEQID NO: 393 IC2 91 (v) V SEQ ID NO: 114 SEQ ID NO: 199 SEQ ID NO: 394 1C304 (vI V SEQ ID NO: 115 SEQ ID NO: 200 SEQ ID NO: 395 IC305(II) || SEQ ID NO: 116 SEQ ID NO: 201 SEQ ID NO: 396 IC306 (Ib lb SEQ ID NO: 117 SEQ ID NO: 202 SEQ ID NO: 397 10361(Ib) lb SEQ ID NO: 118 n.d. SEQ ID NO: 398 IC363(111) 1 SEQ ID NO: 119 nd. SEQ ID NO: 399 1C364 (III) 11 nd. nd. .... ad. IC365 (Ia) la SEQ ID NO: 120 SEQ ID NO: 363 SEQ ID NO: 400 non IC366 (n.t.) typeable n.d. SEQ ID NO: 364 SEQ ID NO: 401 IC367 (I1) It SEQ ID NO: 121 SEQ ID NO: 365 SEQ ID NO: 402 IC368 (Ia) la n.d. n.d. SEQ ID NO: 403 C377 (v) V SEQ ID NO: 122 SEQ ID NO: 366 SEQ ID NO: 404 10379(Ib) lb SEQ ID NO: 123 SEQIDNO:367 SEQ ID NO: 405 10432 (ib) lb SEQ ID NO: 124 SEQ ID NO: 368 SEQ ID NO: 406 10434(III) ndI n.d. n.d. 10455(I1I) liI SEQ ID NO: 125 SEQ ID NO: 369 SEQ ID NO: 407 10457 (II) 1 SEQ ID NO: 126 SEQ ID NO: 370 SEQ ID NO: 408 1C458 (Ia) a SEQ ID NO: 127 SEQ ID NO: 203 SEQ ID NO: 179 IC459(Ib) Ib SEQ ID NO: 128 SEQ ID NO: 371- SEQ ID NO: 409 IC460(11) [I SEQ ID NO: 129 SEQ ID NO: 372 SEQ ID NO: 410 iC461 (Ib) lb SEQ ID NO: 130 SEQ ID NO: 373 SEQ ID NO: 411 Ic462(11) 11 SEQ ID NO: 131 SEQ ID NO: 374 SEQ ID NO: 412 1C463 (Ib) lb n.d. nd. SEQ ID NO: 413 IC469 (V) V n.d SEQ ID NO: 375 SEQ ID NO: 414 C470 (V) V SEQ ID NO: 132 SEQ ID NO: 376 SEQ ID NO: 415 126M4A(Ia) la SEQ ID NO: 94 n.d. SEQ ID NO: 416 5095S2(Ib) lb SEQ ID NO: 96 nd. SEQ ID NO: 417 SEQ ID NO: 97, 6313 (III) SEQ ID NO: 232 SEQ ID NO: 233 SEQ ID NO: 418 12I351 (IV) V SEQ ID NO: 92 nd. SEQ ID NO: 419 NEM316, 12403(111) .. 1 ill nd. nd. SEQ ID NO:234 132 12403/2 (M) Ill SEQ ID NO: 361 nd. SEQ ID NO: 420 12401 (Ib) Ib SEQ ID NO: 93 SEQ ID NO. 185 SEQ ID NO. 176 COH1 (111) MI n.d. ntd. SEQ ID NO. 421 BAA23 (V) V SEQ ID NO. 98 SEQ ID NO. 186 SEQ ID NO. 177 0176H-f4Al) 10 SEQ ID NO. 91 SEQ ID NO. 377 SEQ ID NO. 175 A909 (Ia/c) Ia/c n.d. J n.d. n.d. C388/90 (Ia/c) la/c SEQ ID NO. 100 nd. SEQ ID NO. 422 BAA22 (IlI) IIl nrd. nd. SEQ ID NO. 423 603V/R(V) V SEQ ID NO. 362 SEQ ID NO, 378 SEQ ID NO. 424 49447(V) V SEQ ID NO. 95 n.d. SEQ ID NO. 425 BM61 1(V) V SEQ ID NO. 99 n.d. n.d. Comprises/comprising and grammatical variations thereof when used in this specification are to be taken to specify the presence of stated features, integers, steps or components or groups thereof, but do not preclude the presence or addition of one or more other 5 features, integers, steps, components or groups thereof.

Claims

1. A composition comprising at least two proteins selected from the group consisting of i) a protective protein comprising or consisting of the protective peptide of SEQ ID NO: 1 (gbs0233p) or functionally active variant thereof; ii) a protective protein comprising or consisting of the protective peptide of SEQ 10 ID NO: 2 (gbs1087p) or functionally active variant thereof; iii) a protective protein comprising or consisting of the protective peptide of SEQ ID NO: 3 (gbs1309p) or functionally active variant thereof; iv) a protective protein comprising or consisting of the protective peptide of SEQ ID NO: 4 (gbsl 4 77p) or functionally active variant thereof; 15 v) a protective protein comprising or consisting of the protective peptide of SEQ ID NO: 5 (gbsI478p) or functionally active variant thereoft and vi) a protective protein comprising or consisting of the protective peptide of SEQ ID NO: 6 (gbs20l8p) or functionally active variant thereof. 20

2. The composition of claim 1, wherein the composition comprises at least three proteins selected from the group consisting of subgroup i) to vi).

3. The composition of claim I or 2, wherein the composition comprises at least four proteins selected from the group consisting of subgroup i) to vi). 25

4. The composition of any of claims I to 3, wherein the at least two, three or four proteins are selected from different subgroups i) to vi).

5. The composition of any of claims 1 to 4, wherein at least two of the proteins are 30 selected from one of the subgroups i) to vi).

6. The composition of any of claims I to 5 comprising - at least one protein of subgroup iv); - at least one protein of subgroup vi); 35 - at least one protein of subgroup iv) and at least one protein of subgroup vi); at east one protein or suogroup iv), at east one protem o1 suogroup vi) anu at least one protein of subgroup ii); or - at least one protein of subgroup iv), at least one protein of subgroup vi), at least one protein of subgroup ii) and at least one protein of subgroup v). 5

7. The composition of any of claims I to 6, wherein one of the at least two proteins comprises or consists of the protective peptide of SEQ ID NO: 4 (gbsl477p) or functionally active variant thereof, preferably protective peptide of SEQ ID NO: 4 (gbsI477p) or a naturally occurring variant thereof. 10

8. The composition of any of claims I to 7, wherein one of the at least two proteins comprises or consists of the protective peptide of SEQ ID NO: 6 (gbs2018p) or ftnctionally active variant thereof, preferably protective peptide of SEQ ID NO: 6 (gbs2018p) or a naturally occurring functionally active variant thereof. 15

9. The composition of any of claims I to 8, wherein one of the at least two proteins comprises or consists of the protective peptide of SEQ ID NO: 2 (gbsl087p) or functionally active variant thereof, preferably protective peptide of SEQ ID NO: 2 (gbsl1087p) or a naturally occurring functionally active variant thereof. 20

10. The composition of any of claims 1 to 9, wherein one of the at least two proteins comprises or consists of the protective peptide of SEQ I) NO: 5 (gbs1478p) or functionally active variant thereof, preferably protective peptide of SEQ ID NO: 5 (gbs 1478p) or a naturally occurring functionally active variant thereof. 25

11. The composition of any of claims I to 10, wherein one of the at least two proteins comprises or consists of the protective peptide of SEQ ID NO: 1 (gbs0233p) or functionally active variant thereof, preferably protective peptide of SEQ ID NO: 1 (gbs0233p) or a naturally occurring functionally active variant thereof 30

12. The composition of any of claims I to 11, wherein one of the at least two proteins comprises or consists of the protective peptide of SEQ ID NO: 3 (gbs1309p) or functionally active variant thereof, preferably protective peptide of SEQ ID NO: 3 (gbsl309p) or a naturally occurring functionally active variant thereo-f

13. The composition of any of claims I to 12, wherein the at least two proteins encompass: - the protective peptide of SEQ ID NO: 4 (gbsl477p) and the protective peptide of SEQ ID NO: 6 (gbs20l8p); - the protective peptide of SEQ ID NO: 4 (gbsl477p) and the protective peptide of SEQ ID NO: 6 (gbs2018p) and the protective peptide of SEQ ID NO: 2 (gbs1087p); or - the protective peptide of SEQ ID NO: 4 (gbsl477p) and the protective peptide of SEQ ID NO: 6 (gbs20l8p) and the protective peptide of SEQ ID NO: 2 (gbsl087p) and the protective peptide of SEQ ID NO: 5 (gbs1478p).

14. The composition of any of claims 1 to 13, wherein two or more proteins of the at least two proteins are combined into at least one fusion protein.

15. The composition of any of claims I to 14, wherein the functionally active variant a) is a functionally active fragment of the protective peptide, the functionally active fragment comprising at least 50% of the sequence of the protective peptide, preferably at least 70%, more preferably at least 80%, still more preferably at least 90%, even more preferably at least 95% and most preferably at least 97%, 98% or 99%; b) is derived from the protective peptide by at least one amino acid substitution, addition and/or deletion, wherein the functionally active variant has a sequence identity to the protective peptide or to the functionally active fragment as defined in a) of at least 40%, preferably at least 60%, more preferably at least 75%, still more preferably at least 90%, even more preferably at least 95% and most preferably at least 97%, 98% or 99%; and/or c) consists of the protective peptide or a functionally active variant thereof and additionally at least one amino acid heterologous to the protective peptide, preferably wherein the functionally active variant is derived from or identical to any of the naturally occurring variants of any of the sequences of SEQ ID NO: 55 to 60, 67 to 72, 79 to 84, 91 to 132, 175 to 179, 185 to 203, 223 to 234, and 235 to 425.

16. A protective peptide consisting of the amino acid sequence selected trom the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 55 to 57, 59, 60, 68, 69, 71, 72, 79 to 84, 91 to 132, 175 to 179, 185 to 203, 223 to 234, and 235 to 425. 5

17. One or more nucleic acid(s) encoding the at least two proteins comprised in of the composition according to any of claims I to 15 and/or any of the protective peptides according to claim 16. 10

18. The one or more nucleic acid(s) of claim 17, comprising or consisting of at least one nucleic acid sequence selected from the group consisting of SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: I1, SEQ I) NO: 12, SEQ ID NO: 61 to 66, SEQ ID NO: 73 to 78, SEQ ID NO: 85 to 90, SEQ ID NO: 133 to 174, SEQ ID NO: 180 to 184 and SEQ ID NO: 204 to 222. 15

19. The one or more nucleic acid(s) of claim 17 to 18, wherein the nucleic acid(s) is/are located in a vector or a cell other than .. agalactiae.

20. A method of producing the composition of any of claims I to 15 or the protective 20 peptide of claim 16, comprising (a) introducing the one or more nucleic acids into a host cell; (b) expressing the protein(s) and/or peptide(s) encoded by the nucleic acid by culturing the host cell under conditions conducive to the expression of the protein(s) and/or peptide(s); and 25 (c) collecting and/or isolating the expressed protein(s) and/or peptide(s) of step (b).

21. A pharmaceutical composition, especially a vaccine, comprising (i) the composition according to any of claims 1 to 15 and/or at least one 30 protective peptide according to claim 16; and (ii) optionally a pharmaceutically acceptable carrier or excipient.

22. A pharmaceutical composition comprising (i) the one or more nucleic acid(s) according to any of claims 17 to 19 or one or more nucleic acid(s) complementary thereto, and (ii) optionally a pharmaceutically acceptable carrier or excipient. 5

23. A method for producing antibodies, characterized by the following steps: (a) administering an effective amount of the composition according to any of claims 1 to 15 and/or at least one protective peptide according to claim 16 to an animal; and (b) isolating the antibodies produced by the animal in response to the 10 administration of step (a) from the animal.

24. A method for producing antibodies, characterized by the following steps: (a) contacting a B cell with an effective amount of the composition according to any of claims I to 15 and/or at least one protective peptide according to claim 15 16; (b) fusing the B cell of step (a) with a myeloma cell to obtain a hybridoma cell; and (c) isolating the antibodies produced by the cultivated hybridoma cell. 20

25. The method of claim 23 or 24, wherein the isolated antibodies are additionally purified.

26. A mixture of antibodies against the at least two proteins of the composition of any of claims I to 15 and/or against the at least one protective peptide according to claim 25 16.

27. Use of the composition according to any of claims I to 15 and/or at least one protective peptide according to claim 16 and/or one or more the nucleic acid(s) according to any of claims 17 to 19 for the manufacture of a medicament for the 30 immunization or treatment of a subject, preferably against S. agalactiae, more preferably against pneumonia, septicemia, meningitis, fever, vomiting, poor feeding, irritability, urinary tract infection and/or vaginal infection caused by S. agalactiae.

28. A method of diagnosing a S. agalactiae infection comprising the steps of: (a) contacting a sample obtained from a subject with the composition according to any of claims I to 15 and/or at least one protective peptide according to claim 16; and (b) detecting the presence of an antibody against the protective peptide, the 5 functionally active variant and/or the composition in the sample, wherein the presence of the antibody is indicative for the S. agalactiae infection.

29. A method of diagnosing a S. agalactiae infection comprising the steps of: (a) contacting a sample obtained from a subject with the mixture of antibodies 10 according to claim 26; and (b) detecting the presence of the at least two proteins of the composition of any of claims 1 to 15 and/or of the at least one protective peptide according to claim 16 in the sample, wherein the presence of the at least two proteins is indicative for the S. agalactiae 15 infection.

30. A method for diagnosing an infection with S. agalactiae comprising the steps of: (a) contacting a sample obtained from a subject with a primer and/or a probe specific for the one or more nucleic acid(s) of any of claims 17 to 19; and 20 (b) detecting the presence of one or more nucleic acid(s) of any of claims 17 to 19 in the sample, wherein the presence of the one or more nucleic acid(s) is indicative for the S. agalactiae infection. 25

31. A method for identifying a ligand capable of binding the composition according to any of claims I to 15 and/or at least one protective peptide according to claim 16 comprising: (a) providing a test system comprising the peptide and/or composition, (b) contacting the test system with a test compound, and 30 (c) detecting a signal generated in response to the binding of the test compound to the peptide and/or composition.

32. Use of the composition according to any of claims 1 to 15 and/or at least one protective peptide according to claim 16 for the isolation and/or purification and/or identification of an interaction partner of the composition and/or the peptide.