Molecular characterisation of isoniazid resistant clinical isolates of Mycobacterium tuberculosis from Khyber Pakhtunkhwa, Pakistan.

OBJECTIVE: To investigate the frequency of mutations in catalase-peroxidase and inhibin alpha genes in clinical isolates of isoniazid resistant Mycobacterium tuberculosis strains.

METHODS: The study was conducted at Provincial Tuberculosis Reference Laboratory, Peshawar, Pakistan, from April 2015 to March 2016, and comprised sputum specimens obtained from patients of different ages. All the isolates were analysed for isoniazid resistance. Thirty resistant isolates were randomly selected for mutation analysis of the hotspot regions of catalase-peroxidase and inhibin alpha genes.

RESULTS: Of the 163 positive isolates, 79(48.46%) were resistant to isoniazid. Among these, 21(70%) had mutation in catalase-peroxidase gene and 2(6.6%) had C15T mutation in inhibin alpha promoter region. Among the 21 catalase-peroxidase mutants, Ser315Thr mutation was detected in 15(71.4%) isolates. Gly316Ser mutation was detected in 3(14.2%) isolates. Ser315Arg mutation was identified in 2(9.5%) isolates. Double mutation of Ser303Trp and Lys274Arg was detected in 1(4.7%) isolate. Among the inhibin alpha promoter region mutations, 2(6.6%) of the thirty isolates had the most common C15T mutation in the promoter region.

CONCLUSIONS: One novel mutation at codon 303 in catalase-peroxidase gene was found in the study, and it could contribute to isoniazid resistance.