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. 2023 Oct 17;11(5):e0453122.
doi: 10.1128/spectrum.04531-22. Epub 2023 Sep 6.

Lineage classification and antitubercular drug resistance surveillance of Mycobacterium tuberculosis by whole-genome sequencing in Southern India

Mahadev Rao #  1 , Kurt Wollenberg #  2 , Michael Harris #  2 , Shrivathsa Kulavalli  1 , Levin Thomas  1 , Kiran Chawla  3 , Vishnu Prasad Shenoy  3 , Muralidhar Varma  4 , Kavitha Saravu  4 , H Manjunatha Hande  5 , Chidananda Sanju Shanthigrama Vasudeva  6 , Brendan Jeffrey  2 , Andrei Gabrielian  2 , Alex Rosenthal  2
Affiliations

Lineage classification and antitubercular drug resistance surveillance of Mycobacterium tuberculosis by whole-genome sequencing in Southern India

Mahadev Rao et al. Microbiol Spectr. .

Abstract

Studies mapping genetic heterogeneity of clinical isolates of M. tuberculosis for determining their strain lineage and drug resistance by whole-genome sequencing are limited in high tuberculosis burden settings. We carried out whole-genome sequencing of 242 M. tuberculosis isolates from drug-sensitive and drug-resistant tuberculosis patients, identified and collected as part of the TB Portals Program, to have a comprehensive insight into the genetic diversity of M. tuberculosis in Southern India. We report several genetic variations in M. tuberculosis that may confer resistance to antitubercular drugs. Further wide-scale efforts are required to fully characterize M. tuberculosis genetic diversity at a population level in high tuberculosis burden settings for providing precise tuberculosis treatment.

Keywords: Mycobacterium tuberculosis; antitubercular drug resistance; lineage; tuberculosis; whole genome sequencing.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig 1
Fig 1
Maximum likelihood phylogeny based on WGS data for 242 TB samples plus the H37Rv reference. Major TB lineages are indicated by branch labels. The H37Rv reference is indicated by a dot on the branch tip. Next to the tree are grids indicating drug-sensitivity test (DST) class, district of origin, and drug resistance (DR) single-nucleotide polymorphisms (SNPs). DST is indicated by color according to the legend. Black boxes indicate the district of sample origin. DR SNPs are indicated by a grayscale ranging from black (100% of WGS reads had the SNP) to white (0% of WGS had the DR SNP).
Fig 2
Fig 2
Overall distribution of M. tuberculosis clinical isolates based on lineages.
Fig 3
Fig 3
Frequency of the mutations/combination of mutations identified by WGS that may confer resistance to specific first-line antitubercular drugs, along with their phenotypic concordance (resistance by phenotypic drug sensitivity test). S = Ser; L = Leu; H = His; G = Gly; E = Glu; M = Met; A = Ala; R = Arg; D = Asp; P = Pro; F = Phe, T = Thr; K = Lys; N = Asn; I = Ile; V = Val; Q = Gln; PZA = pyrazinamide
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