Evaluation of inhA gene and catalase-peroxidase gene among isoniazid-sensitive and resistant Mycobacterium tuberculosis isolates.
The katG gene and the inhA gene of 30 INH-resistant (INH-R) and 28 INH-sensitive (INH-S) isolates of M. tuberculosis from Haiti and Maryland were analysed by PCR to establish the presence and frequency of two postulated mechanisms of INH-resistance, total katG gene deletion and inhA Ser94 to Ala94 amino acid substitution. Only two of 30 INH-R isolates (3%) appear to have total katG gene deletions. All 28 INH-S isolates (100%) produced a PCR product at both the 5' and the 3' ends of the katG gene. Gene deletion of katG is a rare mechanism of INH resistance. Allele specific oligonucleotide hybridisation analysis of the inhA PCR products from the same 58 isolates revealed no mutation at amino acid 94 or directly surrounding it. Other inhA gene mutations may be responsible for INH resistance in M. tuberculosis. Diagnostic strategies using katG gene deletion or inhA Ser94 mutations would fail to detect almost all INH-R isolates.
O'Brien
K L
KL
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Dietz
H C
HC
Romagnoli
M
M
Eiden
J
J
D000995:Antitubercular Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D004352:Drug Resistance, Microbial / Q000235:genetics; D017353:Gene Deletion; D005798:Genes, Bacterial / Q000235:genetics; D006205:Haiti; D007538:Isoniazid / Q000494:pharmacology*; D008396:Maryland; D015336:Molecular Probe Techniques; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D010088:Oxidoreductases; D010544:Peroxidases / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D014376:Tuberculosis / Q000382:microbiology
D000995:Antitubercular Agents; D001426:Bacterial Proteins; D010088:Oxidoreductases; D010544:Peroxidases; C076136:catalase HPI; C085257:InhA protein, Mycobacterium; D007538:Isoniazid