Compensatory ahp C Gene Expression in Isoniazid-Resistant Mycobacterium tuberculosis

American Association for the Advancement of Science (AAAS) - Tập 272 Số 5268 - Trang 1641-1643 - 1996
David R. Sherman1, Khisimuzi Mdluli2, Mark J. Hickey1, T M Arain1, Sheldon L. Morris3, Clifton E. Barry2, C. Kendall Stover1
1D. R. Sherman, M. J. Hickey, T. M. Arain, C. K. Stover, Laboratory of Tuberculosis and Molecular Microbiology, PathoGenesis Corporation, 201 Elliott Avenue West, Seattle, WA 98119, USA.
2K. Mdluli and C. E. Barry III, Tuberculosis Research Unit, Laboratory of Intracellular Parasites, National Institutes for Allergy and Infectious Diseases, Rocky Mountain Laboratories, Hamilton, MT 59840, USA.
3S. L. Morris, Laboratory of Mycobacteria, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.

Tóm tắt

Mutations that eliminate KatG catalase-peroxidase activity prevent activation of isoniazid and are a major mechanism of resistance to this principal drug for the treatment of Mycobacterium tuberculosis infections. However, the loss of KatG activity in clinical isolates seemed paradoxical because KatG is considered an important factor for the survival of the organism. Expression of either KatG or the recently identified alkyl hydroperoxidase AhpC was sufficient to protect bacilli against the toxic effects of organic peroxides. To survive during infection, isoniazid-resistant KatG mutants have apparently compensated for the loss of KatG catalase-peroxidase activity by a second mutation, resulting in hyperexpression of AhpC.

Từ khóa


Tài liệu tham khảo

CHAE H.Z., THIOREDOXIN-DEPENDENT PEROXIDE REDUCTASE FROM YEAST, JOURNAL OF BIOLOGICAL CHEMISTRY 269, 27670 (1994).

CHAE H.Z., CLONING AND SEQUENCING OF THIOL-SPECIFIC ANTIOXIDANT FROM MAMMALIAN BRAIN - ALKYL HYDROPEROXIDE REDUCTASE AND THIOL-SPECIFIC ANTIOXIDANT DEFINE A LARGE FAMILY OF ANTIOXIDANT ENZYMES, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 91, 7017 (1994).

CHRISTMAN M.F., POSITIVE CONTROL OF A REGULON FOR DEFENSES AGAINST OXIDATIVE STRESS AND SOME HEAT-SHOCK PROTEINS IN SALMONELLA-TYPHIMURIUM, CELL 41, 753 (1985).

COLE S.T., COMMUNICATION .

DEMPLE B, INDUCIBLE REPAIR OF OXIDATIVE DNA DAMAGE IN ESCHERICHIA-COLI, NATURE 304, 466 (1983).

DERETIC V, MYCOBACTERIUM-TUBERCULOSIS IS A NATURAL MUTANT WITH AN INACTIVATED OXIDATIVE-STRESS REGULATORY GENE - IMPLICATIONS FOR SENSITIVITY TO ISONIAZID, MOLECULAR MICROBIOLOGY 17, 889 (1995).

HALLIWELL B, OXYGEN-TOXICITY, OXYGEN RADICALS, TRANSITION-METALS AND DISEASE, BIOCHEMICAL JOURNAL 219, 1 (1984).

HEYM B, MISSENSE MUTATIONS IN THE CATALASE-PEROXIDASE GENE, KATG, ARE ASSOCIATED WITH ISONIAZID RESISTANCE IN MYCOBACTERIUM-TUBERCULOSIS, MOLECULAR MICROBIOLOGY 15, 235 (1995).

HICKEY M.J., Luciferase in vivo expression technology: Use of recombinant mycobacterial reporter strains to evaluate antimycobacterial activity in mice, ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 40, 400 (1996).

JOHNSSON K, MECHANISTIC STUDIES OF THE OXIDATION OF ISONIAZID BY THE CATALASE PEROXIDASE FROM MYCOBACTERIUM-TUBERCULOSIS, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 116, 7425 (1994).

MORRIS S, MOLECULAR MECHANISMS OF MULTIPLE-DRUG RESISTANCE IN CLINICAL ISOLATES OF MYCOBACTERIUM-TUBERCULOSIS, JOURNAL OF INFECTIOUS DISEASES 171, 954 (1995).

ROSNER J.L., EFFECTS OF PEROXIDES ON SUSCEPTIBILITIES OF ESCHERICHIA-COLI AND MYCOBACTERIUM-SMEGMATIS TO ISONIAZID, ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 38, 1829 (1994).

SHERMAN D.R., DISPARATE RESPONSES TO OXIDATIVE STRESS IN SAPROPHYTIC AND PATHOGENIC MYCOBACTERIA, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 92, 6625 (1995).

SHERMAN D.R. unpublished data.

SHOEB H.A., PEROXIDASE-MEDIATED OXIDATION OF ISONIAZID, ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 27, 399 (1985).

SIES H, BIOCHEMISTRY OF OXIDATIVE STRESS, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 25, 1058 (1986).

TAKAYAMA K, EFFECT ON ISONIAZID ON IN-VIVO MYCOLIC ACID SYNTHESIS, CELL-GROWTH, AND VIABILITY OF MYCOBACTERIUM-TUBERCULOSIS, ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 2, 29 (1972).

WIELES B, IDENTIFICATION AND FUNCTIONAL-CHARACTERIZATION OF THIOREDOXIN OF MYCOBACTERIUM-TUBERCULOSIS, INFECTION AND IMMUNITY 63, 4946 (1995).

WILSON T.M., EFFECT OF INHA AND KATG ON ISONIAZID RESISTANCE AND VIRULENCE OF MYCOBACTERIUM-BOVIS, MOLECULAR MICROBIOLOGY 15, 1009 (1995).

YUAN Y, IDENTIFICATION OF A GENE INVOLVED IN THE BIOSYNTHESIS OF CYCLOPROPANATED MYCOLIC ACIDS IN MYCOBACTERIUM-TUBERCULOSIS, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 92, 6630 (1995).

ZHANG Y, THE CATALASE PEROXIDASE GENE AND ISONIAZID RESISTANCE OF MYCOBACTERIUM-TUBERCULOSIS, NATURE 358, 591 (1992).

Thông tin
Thông tin xuất bản

American Association for the Advancement of Science (AAAS)

Tập 272 Số 5268

1641-1643

Thông tin tác giả