WO1999054479A3 - INHIBITION OF ALKYL HYDROPEROXIDE REDUCTASE, SUBUNIT C (AhpC) TO IMPART SUSCEPTIBILITY TO ANTIMICROBIAL REACTIVE NITROGEN INTERMEDIATES - Google Patents
INHIBITION OF ALKYL HYDROPEROXIDE REDUCTASE, SUBUNIT C (AhpC) TO IMPART SUSCEPTIBILITY TO ANTIMICROBIAL REACTIVE NITROGEN INTERMEDIATES Download PDFInfo
- Publication number
- WO1999054479A3 WO1999054479A3 PCT/US1999/008704 US9908704W WO9954479A3 WO 1999054479 A3 WO1999054479 A3 WO 1999054479A3 US 9908704 W US9908704 W US 9908704W WO 9954479 A3 WO9954479 A3 WO 9954479A3
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- ahpc
- rni
- antimicrobial
- mycobacterium tuberculosis
- reactive nitrogen
- Prior art date
Links
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 title abstract 6
- 230000000845 anti-microbial effect Effects 0.000 title abstract 4
- 239000000543 intermediate Substances 0.000 title abstract 3
- 229910052757 nitrogen Inorganic materials 0.000 title abstract 3
- 102000007456 Peroxiredoxin Human genes 0.000 title 1
- 230000005764 inhibitory process Effects 0.000 title 1
- 108030002458 peroxiredoxin Proteins 0.000 title 1
- 108050003170 Alkyl hydroperoxide reductase subunit C Proteins 0.000 abstract 5
- 108090000623 proteins and genes Proteins 0.000 abstract 5
- 102000004169 proteins and genes Human genes 0.000 abstract 5
- 108020004414 DNA Proteins 0.000 abstract 4
- 241000187479 Mycobacterium tuberculosis Species 0.000 abstract 4
- 239000003814 drug Substances 0.000 abstract 3
- 102000053602 DNA Human genes 0.000 abstract 2
- 229940079593 drug Drugs 0.000 abstract 2
- 229920001184 polypeptide Polymers 0.000 abstract 2
- 108090000765 processed proteins & peptides Proteins 0.000 abstract 2
- 102000004196 processed proteins & peptides Human genes 0.000 abstract 2
- 201000008827 tuberculosis Diseases 0.000 abstract 2
- 206010056663 Gastric infection Diseases 0.000 abstract 1
- -1 antibodies Proteins 0.000 abstract 1
- 238000003556 assay Methods 0.000 abstract 1
- 210000001124 body fluid Anatomy 0.000 abstract 1
- 230000003053 immunization Effects 0.000 abstract 1
- 208000015181 infectious disease Diseases 0.000 abstract 1
- 230000001404 mediated effect Effects 0.000 abstract 1
- 230000001235 sensitizing effect Effects 0.000 abstract 1
- 230000001225 therapeutic effect Effects 0.000 abstract 1
- 229960005486 vaccine Drugs 0.000 abstract 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/0004—Oxidoreductases (1.)
- C12N9/0065—Oxidoreductases (1.) acting on hydrogen peroxide as acceptor (1.11)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
- C12Q1/18—Testing for antimicrobial activity of a material
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Toxicology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biophysics (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
The present invention relates to the use of alkyl hydroperoxide reductase subunit C (AhpC) proteins or polypeptides to confer resistance against antimicrobial reactive nitrogen intermediates (RNI). Also disclosed is a DNA molecule encoding alkyl hydroperoxide reductase subunit C from Mycobacterium tuberculosis and conferring on Mycobacterium tuberculosis resistance to antimicrobial RNI. Such DNA encoding AhpC can be used to screen for drugs that inhibit the ability of AhpC to confer resistance to antimicrobial RNI. Such drugs can be used to treat tuberculosis by sensitizing M. tuberculosis to RNI produced by host cells or delivered therapeutically by inhalation or by oral or other parenteral routes. Alternatively, therapeutics can be developed to treat gastric infection. The protein encoded by this DNA molecule is useful in vaccines to prevent infection by Mycobacterium tuberculosis, while the antibodies raised against this protein can be employed in passively immunizing those already infected by the organism. These proteins, antibodies, and DNA molecules may be utilized in diagnostic assays to detect Mycobacterium tuberculosis in tissue or bodily fluids. The protein or polypeptide is also useful as a therapeutic in treating conditions mediated by the production of reactive nitrogen intermediates.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US8257398P | 1998-04-21 | 1998-04-21 | |
| US60/082,573 | 1998-04-21 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| WO1999054479A2 WO1999054479A2 (en) | 1999-10-28 |
| WO1999054479A9 WO1999054479A9 (en) | 2000-02-10 |
| WO1999054479A3 true WO1999054479A3 (en) | 2001-05-31 |
Family
ID=22172028
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1999/008704 WO1999054479A2 (en) | 1998-04-21 | 1999-04-21 | INHIBITION OF ALKYL HYDROPEROXIDE REDUCTASE, SUBUNIT C (AhpC) TO IMPART SUSCEPTIBILITY TO ANTIMICROBIAL REACTIVE NITROGEN INTERMEDIATES |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO1999054479A2 (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996026275A1 (en) * | 1995-02-22 | 1996-08-29 | Cornell Research Foundation, Inc. | Dna molecule encoding for cellular uptake of mycobacterium tuberculosis and uses thereof |
-
1999
- 1999-04-21 WO PCT/US1999/008704 patent/WO1999054479A2/en active Application Filing
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996026275A1 (en) * | 1995-02-22 | 1996-08-29 | Cornell Research Foundation, Inc. | Dna molecule encoding for cellular uptake of mycobacterium tuberculosis and uses thereof |
Non-Patent Citations (8)
| Title |
|---|
| CHEN ET AL.: "Alkyl hydroxyperoxide reductase subunit C (AHPC) from Mycobacterium tuberculosis protects mammalian cells against reactive nitrogen intermediates", JAPANESE JOURNAL OF PHARMACOLOGY, vol. 75, no. S1, 1997, JAPANESE PHARMACOLOGY SOCIETY; KYOTO, JAPAN, pages 91P, XP002116778 * |
| D.R. SHERMAN ET AL.: "Compensatory ahpC gene expression in Isoniazid-resistant Mycobacterium tuberculosis", SCIENCE, vol. 272, 14 June 1996 (1996-06-14), AAAS,WASHINGTON,DC,US, pages 1641 - 1643, XP002116689 * |
| K. HUYGEN ET AL.: "Immunogenecity and protective efficacy of a tuberculosis DNA vaccine", NATURE MEDICINE, vol. 2, no. 8, August 1996 (1996-08-01), NATURE PUBLISHING CO., NY, US, pages 893 - 898, XP002116692 * |
| L. CHEN ET AL.: "Alkyl hydroperoxide reductase subunit C (AhpC) protects bacterial and human cells against reactive nitrogen intermediates", MOLECULAR CELL, vol. 1, no. 6, May 1998 (1998-05-01), CELL PRESS, CAMBRIDGE, MA, US, pages 795 - 805, XP002116693 * |
| R.E. TASCON ET AL.: "Vaccination against tuberculosis by DNA injection", NATURE MEDICINE, vol. 2, no. 8, August 1996 (1996-08-01), NATURE PUBLISHING CO., NY, US, pages 888 - 892, XP002116691 * |
| S. DHANDAYUTHAPANI ET AL.: "Oxidatice stress response and its role in sensitivity to isoniazid in Mycobacteria: Characterization and inducibility of ahpC by peroxides in Mycobacterium smegmatis and lach of expression in M.aurum and M.tuberculosis", J. BACTERIOL., vol. 178, no. 12, June 1996 (1996-06-01), AM. SOC. MICROBIOL.,BALTIMORE,US;, pages 3641 - 3649, XP002116687 * |
| S.T. COLE ET AL.: "Mycobacterium tuberculosis H37Rv complete genome; segment 107/162", EMBL DATABASE, 5 November 1996 (1996-11-05), Cambrisge, UK, XP002116690 * |
| V. DERETIC ET AL.: "Mycobacterium tuberculosis is a natural mutant with an inactivated oxidative-stress regulatory gene: implications for sensitivity to isoniazid", MOLECULAR MICROBIOL., vol. 17, no. 5, 1995, BLACKWELL, OXFORD, GB, pages 889 - 900, XP002116688 * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO1999054479A9 (en) | 2000-02-10 |
| WO1999054479A2 (en) | 1999-10-28 |
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