Investigation of Ser315 Substitutions withinkatGGene in Isoniazid-Resistant Clinical Isolates ofMycobacterium tuberculosisfrom South India

Abstract

Mutation at codon 315 ofkatGgene is the major cause for isoniazid (INH) resistance inMycobacterium tuberculosis(M. tuberculosis). Substitution at codon 315 ofkatGgene was analyzed in 85 phenotypically resistant isolates collected from various parts of southern India by direct sequencing method. The obtained results were interpreted in the context of minimum inhibitory concentration (MIC) of INH. Of the 85 phenotypically resistant isolates, 56 (66%) were also correlated by the presence of resistance mutations in thekatGgene; 47 of these isolates had ACC, 6 had AAC, 2 had ATC, and one had CGC codon. The frequency of Ser315 substitution inkatGgene was found to be higher (70%) amongst multidrug-resistant (MDR) strains than among non-MDR (61%) INH-resistant isolates. Further, the frequency of mutations was found to be greater (74%) in isolates with higher MIC values in contrast to those isolates with low MIC values (58%). Therefore, the study identified high prevalence of Ser315Thr substitution inkatGgene of INH-resistant isolates from south India. Also, isolates harboring this substitution were found to be associated with multidrug and high level INH resistance.