title: Compensatory ahpC gene expression in isoniazid-resistant Mycobacterium tuberculosis.
abstract: 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.
authors.affiliation: Laboratory of Tuberculosis and Molecular Microbiology, PathoGenesis Corporation, Seattle, Washington 98119, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Sherman
authors.forename: K
authors.initials: K
authors.lastname: Mdluli
authors.forename: M J
authors.initials: MJ
authors.lastname: Hickey
authors.forename: T M
authors.initials: TM
authors.lastname: Arain
authors.forename: S L
authors.initials: SL
authors.lastname: Morris
authors.forename: C E
authors.initials: CE
authors.lastname: Barry
authors.forename: C K
authors.initials: CK
authors.lastname: Stover
mesh_terms: D000595:Amino Acid Sequence; D000995:Antitubercular Agents / Q000494:pharmacology*; D001426:Bacterial Proteins; D001483:Base Sequence; D003001:Cloning, Molecular; D004269:DNA, Bacterial; D004352:Drug Resistance, Microbial / Q000235:genetics; D004357:Drug Synergism; D004790:Enzyme Induction; D015964:Gene Expression Regulation, Bacterial; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007538:Isoniazid / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009154:Mutation; D009163:Mycobacterium bovis / Q000187:drug effects / Q000235:genetics; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics*; D010088:Oxidoreductases / Q000235:genetics*; D010544:Peroxidases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D054464:Peroxiredoxins; D011401:Promoter Regions, Genetic
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D006861:Hydrogen Peroxide; D010088:Oxidoreductases; D010544:Peroxidases; D054464:Peroxiredoxins; C076136:catalase HPI; D007538:Isoniazid