Usefulness of Mycobacterium Tuberculosis Genomic Mutations in the Genes katG and inhA for the Prediction of Isoniazid Resistance

Int J Tuberc Lung Dis. 1997 Aug;1(4):365-9.

Abstract

Setting: Mutations in two genes of Mycobacterium tuberculosis, inhA and katG, are known to correlate with resistance to isoniazid (INH).

Objective: To determine which mutation or mutations are the most predictive for INH resistance and the most frequent ones in such isolates. Further, to propose a simple and generally applicable method for their detection.

Design: Codons 94 and 95 in the inhA gene and codons 315 and 463 in the katG gene were characterized in 50 INH-resistant and 12 INH-sensitive isolates from Germany and Sierra Leone.

Results: Mutations in codon 315 of the katG gene were detected in 27 of the INH-resistant and none of the INH-sensitive isolates. All mutations in this codon altered an AciI restriction enzyme site. No mutations were found in the investigated codons of the inhA gene.

Conclusion: We propose that most INH resistances can be rapidly predicted by a simple AciI restriction enzyme digest of a polymerase chain reaction (PCR)-amplified katG fragment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / therapeutic use*
  • Bacterial Proteins / genetics*
  • Codon / genetics
  • Cross-Cultural Comparison
  • DNA Mutational Analysis
  • Germany
  • Humans
  • Isoniazid / therapeutic use*
  • Mutagenesis, Site-Directed*
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / genetics*
  • Oxidoreductases*
  • Peroxidases / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Sierra Leone
  • Tuberculosis, Multidrug-Resistant / microbiology*

Substances

  • Antitubercular Agents
  • Bacterial Proteins
  • Codon
  • Oxidoreductases
  • Peroxidases
  • catalase HPI
  • InhA protein, Mycobacterium
  • Isoniazid