Mutations in the Catalase-Peroxidase Gene From Isoniazid-Resistant Mycobacterium Tuberculosis Isolates

J Infect Dis. 1994 May;169(5):1162-5. doi: 10.1093/infdis/169.5.1162.

Abstract

Isoniazid resistance in Mycobacterium tuberculosis has been associated with total deletion of the katG gene, which codes for catalase-peroxidase production. To determine whether this is a common mechanism of drug resistance, 9 isolates of isoniazid-resistant and 1 of isoniazid-sensitive M. tuberculosis were analyzed by polymerase chain reaction amplification of a 237-bp sequence of the katG gene. Amplification was observed in the isoniazid-sensitive isolate and in 8 resistant isolates; in only 1 isoniazid-resistant isolate was there no amplification of the expected band, suggesting gene deletion. DNA sequencing showed that 8 of the 9 isolates had point mutations, deletions, or insertions of 1-3 bases. Evidence corroborating the presence of mutations in the katG gene was obtained by single-strand conformation polymorphism analysis in these 8 isolates. Thus, mutations as well as insertions and deletions in the katG gene can account for inactive catalase peroxidase, leading to isoniazid resistance; gene deletion occurs only infrequently, in approximately 11% of cases.

MeSH terms

  • Bacterial Proteins*
  • Base Sequence
  • Catalase / genetics*
  • DNA, Bacterial
  • Drug Resistance, Microbial / genetics
  • Genes, Bacterial
  • Isoniazid / pharmacology*
  • Molecular Sequence Data
  • Mutation*
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / enzymology*
  • Mycobacterium tuberculosis / genetics
  • Peroxidases / genetics*
  • Polymerase Chain Reaction

Substances

  • Bacterial Proteins
  • DNA, Bacterial
  • Peroxidases
  • Catalase
  • catalase HPI
  • Isoniazid

Associated data

  • GENBANK/L24503
  • GENBANK/L24504
  • GENBANK/L24505
  • GENBANK/L24506
  • GENBANK/L24507
  • GENBANK/L24508
  • GENBANK/L24509
  • GENBANK/L24510