The mutations of katG and inhA genes of isoniazid-resistant Mycobacterium tuberculosis isolates in Taiwan.

Background/purpose: The isoniazid (INH) resistance of Mycobacterium tuberculosis is caused by mutations in the katG and inhA genes encoding for catalase-peroxidase and inhA, respectively. Sequences of the katG and inhA gene of 70 isolates were analyzed to identify the mutations and to compare the mutations with their related susceptibilities.

Methods: Sequences of the katG and inhA genes and the resistance profiles were analyzed for the 70 M. tuberculosis isolates, collected from nine hospitals in Taiwan during the period from 1999 to 2011.

Results: Fifteen alleles were identified in the katG gene and two alleles were identified in the inhA gene. Among the 15 alleles identified in the katG gene, 14 alleles were found in isolates resistant to isoniazid, while only three alleles were found in isolates susceptible to isoniazid. The mutations of the katG gene and their frequencies of 41 INH-resistant isolates were Arg463Leu (51%), Ser315Thr (29%), Ser315Asn (9.8%), and other loci (22%). The sensitivity and specificity of the Ser315Thr mutation for the detection of INH-resistant isolates were 29% and 100%, respectively. The frequency of inhA gene mutation was low (2.44%) in the 41 INH-resistant isolates.

Conclusion: The diverse alleles of the katG gene associated with INH resistance are present in the M. tuberculosis isolates in Taiwan. These data may be applied to develop new probes for various alleles associated with INH resistance in order to increase the sensitivity for the detection of genetically diverse M. tuberculosis isolates in different geographic areas. The diversity of mutations can also provide information for investigating the evolutional lineages of M. tuberculosis isolates.