Isoniazid MIC and KatG Gene Mutations among Mycobacterium tuberculosis Isolates in Northwest of Iran

Isoniazid (INH) is one of the main first line drugs used in treatment of tuberculosis and development of resistance against this compound can result in serious problems in treatment procedures. Resistance to INH is mediated mainly by mutation in KatG gene that is coded for the catalase enzyme. The proportional method for detection of INH-resistance is time consuming due to the slow growth rate of Mycobacterium tuberculosis. In this study, we used PCR-RFLP approach for screening of common mutations in KatG gene for detection of INH resistance, and compared the results to minimal inhibitory concentration (MIC) in M. tuberculosis isolates.

Fifty M. tuberculosis isolates were subjected to study of which, 25 strains were INH-resistant and 25 strains were INH-sensitive.

Of 25 INH-resistant strains, the mutation was identified in 56% and 20% in the KatG315 and KatG463 loci, respectively. In 24% of INH-resistant strains, no mutation was observed in the studied loci. INH MIC was <0.2 μg/ml in all sensitive strains whereas among 25 INH -resistant isolates, INH MIC was higer than 0.2 μg/ml ranged from 0.2 to 3.2 μg/ml.

Our findings revealed that PCR-RFLP is capable to identify INH-resistance in more than 76% of INH- resistant M. tuberculosis strains, and could be used for rapid identification of INH resistance. High levels of INH MIC were observed in the strains which had mutation in the KatG gene in position 315.