ahpC, a gene involved in isoniazid resistance of the Mycobacterium tuberculosis complex

Mol Microbiol. 1996 Mar;19(5):1025-34. doi: 10.1046/j.1365-2958.1996.449980.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bacterial Proteins / genetics
  • Base Sequence
  • DNA, Bacterial
  • Drug Resistance, Microbial / genetics
  • Genes, Bacterial
  • Humans
  • Isoniazid / pharmacology*
  • Molecular Sequence Data
  • Mutation
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / genetics*
  • Oxidoreductases / genetics*
  • Peroxidases / genetics
  • Peroxiredoxins
  • Promoter Regions, Genetic
  • Sequence Homology, Amino Acid


  • Bacterial Proteins
  • DNA, Bacterial
  • Oxidoreductases
  • Peroxidases
  • Peroxiredoxins
  • catalase HPI
  • InhA protein, Mycobacterium
  • Isoniazid

Associated data

  • GENBANK/U24083
  • GENBANK/U24084
  • GENBANK/U24085