TY - JOUR
T1 - Whole genome sequencing of Mycobacterium tuberculosis clinical isolates from India reveals genetic heterogeneity and region-specific variations that might affect drug susceptibility
AU - Advani, Jayshree
AU - Verma, Renu
AU - Chatterjee, Oishi
AU - Pachouri, Praveen Kumar
AU - Upadhyay, Prashant
AU - Singh, Rajesh
AU - Yadav, Jitendra
AU - Naaz, Farah
AU - Ravikumar, Raju
AU - Buggi, Shashidhar
AU - Suar, Mrutyunjay
AU - Gupta, Umesh D.
AU - Pandey, Akhilesh
AU - Chauhan, Devendra S.
AU - Tripathy, Srikanth Prasad
AU - Gowda, Harsha
AU - Prasad, T. S.Keshava
N1 - Funding Information:
This work was supported by internal funding from Yenepoya (Deemed to be University) and the Olav Thon Foundation grant on “Discovering new therapeutic targets and drugs to combat AMR tuberculosis.” JA is a recipient of Senior Research Fellowship from Council of Scientific & Industrial Research (CSIR) Government of India. RV is a recipient of
Publisher Copyright:
Copyright © 2019 Advani, Verma, Chatterjee, Pachouri, Upadhyay, Singh, Yadav, Naaz, Ravikumar, Buggi, Suar, Gupta, Pandey, Chauhan, Tripathy, Gowda and Prasad.
PY - 2019
Y1 - 2019
N2 - Whole genome sequencing (WGS) of Mycobacterium tuberculosis has been constructive in understanding its evolution, genetic diversity and the mechanisms involved in drug resistance. A large number of sequencing efforts from across the globe have revealed genetic diversity among clinical isolates and the genetic determinants for their resistance to anti-tubercular drugs. Considering the high TB burden in India, the availability of WGS studies is limited. Here we present, WGS results of 200 clinical isolates of M. tuberculosis from North India which are categorized as sensitive to first-line drugs, mono-resistant, multi-drug resistant and pre-extensively drug resistant isolates. WGS revealed that 20% of the isolates were co-infected with M. tuberculosis and non-tuberculous mycobacteria species. We identified 12, 802 novel genetic variations in M. tuberculosis isolates including 343 novel SNVs in 38 genes which are known to be associated with drug resistance and are not currently used in the diagnostic kits for detection of drug resistant TB. We also identified M. tuberculosis lineage 3 to be predominant in the northern region of India. Additionally, several novel SNVs, which may potentially confer drug resistance were found to be enriched in the drug resistant isolates sampled. This study highlights the significance of employing WGS in diagnosis and for monitoring further development of MDR-TB strains.
AB - Whole genome sequencing (WGS) of Mycobacterium tuberculosis has been constructive in understanding its evolution, genetic diversity and the mechanisms involved in drug resistance. A large number of sequencing efforts from across the globe have revealed genetic diversity among clinical isolates and the genetic determinants for their resistance to anti-tubercular drugs. Considering the high TB burden in India, the availability of WGS studies is limited. Here we present, WGS results of 200 clinical isolates of M. tuberculosis from North India which are categorized as sensitive to first-line drugs, mono-resistant, multi-drug resistant and pre-extensively drug resistant isolates. WGS revealed that 20% of the isolates were co-infected with M. tuberculosis and non-tuberculous mycobacteria species. We identified 12, 802 novel genetic variations in M. tuberculosis isolates including 343 novel SNVs in 38 genes which are known to be associated with drug resistance and are not currently used in the diagnostic kits for detection of drug resistant TB. We also identified M. tuberculosis lineage 3 to be predominant in the northern region of India. Additionally, several novel SNVs, which may potentially confer drug resistance were found to be enriched in the drug resistant isolates sampled. This study highlights the significance of employing WGS in diagnosis and for monitoring further development of MDR-TB strains.
KW - Fluoroquinolones
KW - Metagenomics
KW - Molecular genotyping
KW - Mycobacterial genetic heterogeneity
KW - Next generation sequencing
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U2 - 10.3389/fmicb.2019.00309
DO - 10.3389/fmicb.2019.00309
M3 - Article
AN - SCOPUS:85065925148
SN - 1664-302X
VL - 10
JO - Frontiers in Microbiology
JF - Frontiers in Microbiology
IS - FEB
M1 - 309
ER -