Molecular analysis of isoniazid-resistant clinical isolates of Mycobacterium tuberculosis from India

The presence of mutations in specific regions of katG, inhA, oxyR-ahpC and kasA associated with isoniazid (INH)-resistant clinical isolates of Mycobacterium tuberculosis from India were analysed by DNA sequencing. Point mutations in the katG gene at codon 315 and a mutation at codon 138 were detected in 64.3% (45/70) and 4% (1/25) of isolates, respectively. Polymorphisms at codon 463 of the katG gene were found both in resistant and sensitive isolates. Mutation at the inhA and oxyR-ahpC promoter regions occurred in 11.4% (8/70) and 35.0% (14/40) of the isolates, respectively. No mutation was found to occur in kasA and inhA structural gene regions. Of the 70 resistant isolates studied, 55 (78.6%) showed mutation in the regions sequenced. This is the first comprehensive molecular analysis of INH resistance in India, which suggests that point mutation rather than deletion and insertion is the major cause of INH resistance.