Molecular characterization of isoniazid-resistant Mycobacterium tuberculosis clinical strains isolated in the Philippines

Int J Antimicrob Agents. 2004 Jun;23(6):572-6. doi: 10.1016/j.ijantimicag.2003.09.032.

Abstract

The prevalence of mutations in the katG, inhA and oxyR-ahpC genes of isoniazid (INH)-resistant Mycobacterium tuberculosis isolates in the Philippines were determined. Of 306 M. tuberculosis isolates studied, 81 (26.5%) exhibited INH-resistance. Forty-four strains (54.3%) had mutations in the katG gene, eighteen strains (22.2%) had mutations in the putative inhA locus region, seven had mutations in both regions and five strains had mutations in the oxyR-ahpC operon. Only seven strains had no mutations. A total of 71 of the 81 (87.6%) resistant strains and 65 of the 72 (90.3%) INH sensitive randomly selected strains showed amino acid substitution in codon 463 (Arg to Leu) (88.9%). This fact supports the hypothesis that mutations at codon 463 are independent of INH-resistance and are linked to the geographical origins of the strains.

MeSH terms

  • Amino Acid Substitution
  • Antitubercular Agents / pharmacology*
  • Bacterial Proteins / genetics
  • Catalase / genetics
  • DNA Fingerprinting
  • DNA, Bacterial / analysis
  • DNA, Bacterial / isolation & purification
  • Drug Resistance, Bacterial / genetics*
  • Humans
  • Isoniazid / pharmacology*
  • Molecular Epidemiology
  • Mutation
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / genetics*
  • Mycobacterium tuberculosis / isolation & purification
  • Operon
  • Oxidoreductases / genetics
  • Philippines
  • Point Mutation
  • Polymorphism, Restriction Fragment Length
  • Repressor Proteins / genetics
  • Sequence Analysis, DNA
  • Tuberculosis / microbiology

Substances

  • Antitubercular Agents
  • Bacterial Proteins
  • DNA, Bacterial
  • Repressor Proteins
  • Oxidoreductases
  • Catalase
  • katG protein, Mycobacterium tuberculosis
  • InhA protein, Mycobacterium
  • Isoniazid