Usefulness of Mycobacterium tuberculosis genomic mutations in the genes katG and inhA for the prediction of isoniazid resistance.

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.