Elucidation of drug resistant mutations of Mycobacterium tuberculosis by whole genome sequencing from North India.
Sethi S., Hao Y., Brown SM., Walker T., Yadav R., Zaman K., Aggarwal AN., Behera D.
INTRODUCTION:Rapid diagnosis of drug resistant tuberculosis is required for better patient management and treatment outcome. Whole-genome sequencing (WGS) can detect single nucleotide polymorphisms (SNPs) and deletions/insertions which are responsible for mostMycobacterium tuberculosis drug resistance. WGS is being performed at scale in high-income countries but there are still limited reports of its use in India. METHOD:In this study, 33 clinicalM. tuberculosis isolates were taken from Mycobacterial repository in Chandigarh and were whole-genome sequenced. Phenotypic drug susceptibility testing was performed according to WHO recommendations. Four were considered culture contaminated. RESULTS:Among the other 29 isolates, 21(72.4%) were multi-drug resistance (MDR-TB) and one was extensively-drug resistant (XDR-TB). The most common mutations observed for isoniazid, rifampicin, ofloxacin and kanamycin werekatG_S315 T, rpoB_S450 L, gyrA_A90 V and rrs_A1401 G respectively. The isolates belonged to lineage 2 and 3, with most MDR-TB among lineage 2 isolates. CONCLUSION:Whole-Genome Sequencing ofMycobacterium tuberculosis offers the detection of drug resistance to all drugs in a single test and also provides insight into the evolution and drug-resistant tuberculosis.