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 PDF

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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
Application number
PCT/US1999/008704
Other languages
French (fr)
Other versions
WO1999054479A2 (en
WO1999054479A9 (en
Inventor
Carl F Nathan
Qiao-Wen Xie
Lei Chen
Original Assignee
Cornell Res Foundation Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Cornell Res Foundation Inc filed Critical Cornell Res Foundation Inc
Publication of WO1999054479A2 publication Critical patent/WO1999054479A2/en
Publication of WO1999054479A9 publication Critical patent/WO1999054479A9/en
Publication of WO1999054479A3 publication Critical patent/WO1999054479A3/en

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Classifications

    • 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

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  • 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.
PCT/US1999/008704 1998-04-21 1999-04-21 INHIBITION OF ALKYL HYDROPEROXIDE REDUCTASE, SUBUNIT C (AhpC) TO IMPART SUSCEPTIBILITY TO ANTIMICROBIAL REACTIVE NITROGEN INTERMEDIATES WO1999054479A2 (en)

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

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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)

* Cited by examiner, † Cited by third party
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

Patent Citations (1)

* Cited by examiner, † Cited by third party
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)

* Cited by examiner, † Cited by third party
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
WO1999054479A2 (en) 1999-10-28
WO1999054479A9 (en) 2000-02-10

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