title: ahpC, a gene involved in isoniazid resistance of the Mycobacterium tuberculosis complex.
abstract: A gene conferring low-level isoniazid (INH) resistance on Mycobacterium smegmatis was isolated from a cosmid library of the genome of an INH-resistant Mycobacterium bovis strain. The gene had good homology with ahpC, the product of which is a subunit of alkyl hydroperoxide reductase, and also with a family of thiol-specific antioxidant enzymes. A mutation was found in the promoter upon comparison with the equivalent DNA sequence from the INH-sensitive parent strain. Promoter sequences from other INH-sensitive and INH-resistant M. bovis and Mycobacterium tuberculosis strains were sequenced and the mutation was found only in the INH-resistant strains. An INH-resistant M. tuberculosis strain also had an additional mutation in the promoter region. The wild-type promoter and promoters with one and two mutations were ligated into a reporter plasmid containing the lacZ gene. The presence of the first mutation resulted in a sixfold induction of beta-galactosidase activity, and the presence of both mutations caused a 10-fold induction. Increased expression of AhpC may account for some of the INH resistance of strains of the M. tuberculosis complex.
authors.affiliation: AgResearch, Wallaceville Animal Research Centre, Upper Hutt, New Zealand.
authors.forename: T M
authors.initials: TM
authors.lastname: Wilson
authors.forename: D M
authors.initials: DM
authors.lastname: Collins
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D001483:Base Sequence; D004269:DNA, Bacterial; D004352:Drug Resistance, Microbial / Q000235:genetics; D005798:Genes, Bacterial; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics*; D010088:Oxidoreductases / Q000235:genetics*; D010544:Peroxidases / Q000235:genetics; D054464:Peroxiredoxins; D011401:Promoter Regions, Genetic; D017386:Sequence Homology, Amino Acid
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D010088:Oxidoreductases; D010544:Peroxidases; D054464:Peroxiredoxins; C076136:catalase HPI; C085257:InhA protein, Mycobacterium; D007538:Isoniazid