Characterisation of M. tuberculosis isolates obtained from Tamil Nadu prevalence survey by whole genome sequencing analysis.

Recent advances in whole genome sequencing have facilitated the understanding of drug resistance patterns and lineage distribution of M. tuberculosis worldwide. In this study, we aimed to determine the genetic diversity of MTB isolates from presumptive pulmonary TB patients obtained from a state prevalence survey. A total of 124 isolates were available for further characterisation, out of which 71 (57.2 %) and 47 (37.9 %) were subjected to sequencing and phenotypic DST, respectively. The phenotypic resistance profile revealed 3 isolates with multidrug resistance and 3 with mono-INH resistance. Out of 71 isolates, sequencing data were available for 61 (85.9 %), where the lineage distribution and drug resistance profile were analysed in comparison with phenotypic DST results. All the mutations were significant, accounting for one or the other resistance pattern. The concordance between pDST and gDST for the drugs was above 90 % except for ETH (77 %) and INH (87 %). The phylogenetic analysis of the lineage distribution revealed three clusters with MDR isolates belonging to lineage 1 and lineage 3. While lineage 2 is more frequently associated with MDR distribution both in India and worldwide, we did not find any lineage 2 MDR-TB isolates in our study. The use of WGS analysis improved our understanding of the genetic characteristics of MTB and its correlation with DR-TB transmission.