Introduction
The mechanistic details of first line drug (FLD) resistance have been thoroughly explored but the genetic resistance mechanisms of second line injectables, which form the backbone of the combinatorial drug resistant tuberculosis therapy, are partially identified. This study aims to highlight the genetic and spoligotypic differences in the second line drug (SLD) resistant and sensitive
Mycobacterium tuberculosis
(
Mtb)
clinical isolates from Mumbai (Western India) and Lucknow (Northern India).
Methods
The
rrs, eis, whiB7, tlyA, gyrA
and
gyrB
target loci were screened in 126 isolates and spoligotyped.
Results
The novel mutations were observed in
whiB7
loci (A43T, C44A, C47A, G48T, G59A and T152G in 5’-UTR; A42C, C253T and T270G in gene),
tlyA
(+CG200, G165A, C415G, and +G543) and
gyrB
(+G1359 and +A1429). Altogether, the
rrs, eis
, and
whiB7
loci harbored mutations in ~86% and ~47% kanamycin resistant isolates from Mumbai and Lucknow, respectively. Mumbai strains displayed higher prevalence of mutations in
gyrA
(~85%) and
gyrB
loci (~13%) as compared to those from Lucknow (~69% and ~3.0%, respectively). Further, spoligotyping revealed that Beijing lineage is distributed equally amongst the drug resistant strains of Mumbai and Lucknow, but EAI-5 is existed at a higher level only in Mumbai. The lineages Manu2, CAS1-Delhi and T1 are more prevalent in Lucknow.
Conclusion
Besides identifying novel mutations in
whiB7, tlyA
and
gyrB
target loci, our analyses unveiled a potential polymorphic and phylogeographical demarcation among two distinct regions.