Mycobacterium tuberculosis Complex Mutations in Drug Resistant Clinical Isolates from Southwest Mexico

Abstract

Mutations in target genes have been described in Mycobacterium tuberculosis Complex (MTBc) drug resistant isolates worldwide. In Mexico, not enough information has been reported in this concern. The aim of this study was to characterize mutations related to resistance to first line drugs in MTBc isolates from Oaxaca, Mexico. MTBc isolates were identified in clinical samples from Tuberculosis (TB) patients. Susceptibility to isoniazid, rifampin, ethambutol, streptomycin and pyrazinamide was tested through nitrate reductase assay. PCR based analysis and sequencing were employed to characterize mutations in katG, inhA, rpoB, embB, rrs, rpsL and pncA genes. Mutations in katG and the promoter of the mabA-inhA operon were found in isoniazid resistant isolates. Sequence analysis of Rifampin Resistance-Determining Region in the rpoB gene showed novel mutations along this region besides mutations at codons 516, 526 and 531. Polymorphisms at codon 306 embB gene were found in ethambutol resistant isolates. Frequent mutations associated to resistance to streptomycin were characterized in rrs and/or rpsL genes. pncA analysis showed variable number of mutations in resistant and susceptible pyrazinamide isolates. Most frequent mutations related to resistance to first line antituberculous drugs were identified in phenotypically resistant MTBc isolates. New mutations were characterized in rpoB, rrs and rpsL genes.