Frequency of mutations in rifampicin and isoniazid resistant isolates of M. tuberculosis: an analysis from Central India.

Abstract

The spread of drug-resistant tuberculosis has challenged tuberculosis control strategies globally. The present study aims to analyze the frequency of mutations in rpoB, katG and inhA genes in strains of M. tuberculosis complex (MTBC) circulating in Central India. It is anticipated that the findings may provide a starting point to understand the evolutionary success of drug-resistant strains of MTBC in this region. Line probe assay was carried out on 720 consecutive sputum samples of MDR suspects from June 2012 to May 2013. Mutation frequencies in the rpoB, katG and inhA genes were analyzed. Mutations were identified in 269 (37.6%) samples, as follows: 55 (7.6%) samples had mutations conferring resistance to only isoniazid, 84 (11.6%) had mutations conferring resistance to only rifampicin and 130 (18%) isolates had mutations conferring resistance to both isoniazid and rifampicin. The most frequent mutation in the rpoB gene was at codon S531L, seen in 141 (19.5%) isolates. The most frequent mutation in the katG gene was at codon S315T1, seen in 151 (20.9%) isolates; and in the inhA gene at codon C15T, seen in 21 (2.9%) isolates. Some unidentified mutations were also observed. The patterns and the frequency of the mutations identified in this study indicate the most frequent mutations at S531L codon in the rpoB gene, S315T1 codon in the katG gene and C15T codon in the promoter region of the inhA gene. Controlling the emergence and spread of MDR TB requires an understanding of the evolution of these mutations.