Elucidation of drug resistance mutations in Mycobacterium tuberculosis isolates from North India by whole-genome sequencing

Objectives: Rapid diagnosis of drug-resistant tuberculosis (TB) is required for better patient management and treatment outcomes. Whole-genome sequencing (WGS) can be used to detect single nucleotide polymorphisms (SNPs) and deletions/insertions that are responsible for mostMycobacterium tuberculosi...

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Main Authors: Sunil Sethi, Yuhan Hao, Stuart M. Brown, Timothy Walker, Rakesh Yadav, Kamran Zaman, Ashutosh Nath Aggarwal, Digambar Behera
Format: Article
Language:English
Published: Elsevier 2020-03-01
Series:Journal of Global Antimicrobial Resistance
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2213716519301298
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author Sunil Sethi
Yuhan Hao
Stuart M. Brown
Timothy Walker
Rakesh Yadav
Kamran Zaman
Ashutosh Nath Aggarwal
Digambar Behera
author_facet Sunil Sethi
Yuhan Hao
Stuart M. Brown
Timothy Walker
Rakesh Yadav
Kamran Zaman
Ashutosh Nath Aggarwal
Digambar Behera
author_sort Sunil Sethi
collection DOAJ
description Objectives: Rapid diagnosis of drug-resistant tuberculosis (TB) is required for better patient management and treatment outcomes. Whole-genome sequencing (WGS) can be used to detect single nucleotide polymorphisms (SNPs) and deletions/insertions that are responsible for mostMycobacterium tuberculosis drug resistance. WGS is being performed at scale in high-income countries, but there are limited reports of its use in India. Methods: In this study, 33 clinicalM. tuberculosis isolates from the Mycobacterial Repository in Chandigarh underwent WGS. Phenotypic drug susceptibility testing was performed according to World Health Organization (WHO) recommendations. Four isolates were excluded from the analysis due to culture contamination or mislabelling during the study. Results: Among the remaining 29 isolates, 21 (72.4%) were multidrug-resistant TB (MDR-TB) and 1 (3.4%) was extensively-drug resistant TB (XDR-TB). The most common mutations observed for isoniazid, rifampicin, ofloxacin and kanamycin resistance werekatG(S315T), rpoB(S450L), gyrA(A90V) and rrs(A1401G), respectively. The isolates mainly belonged to lineages 2 and 3, with most MDR-TB among lineage 2 isolates. Conclusion: WGS ofM. tuberculosis isolates allows the detection of drug resistance to all drugs in a single test and also provides insight into the evolution and drug-resistant TB.
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spelling doaj.art-eb44ee44a1d24e78b6e37c6fd7c368e62022-12-21T18:51:14ZengElsevierJournal of Global Antimicrobial Resistance2213-71652020-03-01201115Elucidation of drug resistance mutations in Mycobacterium tuberculosis isolates from North India by whole-genome sequencingSunil Sethi0Yuhan Hao1Stuart M. Brown2Timothy Walker3Rakesh Yadav4Kamran Zaman5Ashutosh Nath Aggarwal6Digambar Behera7Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India; Corresponding author.Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY 10003, USA; Applied Bioinformatics Laboratories, New York University School of Medicine, NY 10016, USAApplied Bioinformatics Laboratories, New York University School of Medicine, NY 10016, USA; Department of Cell Biology, New York University School of Medicine, NY 10016, USADepartment of Microbiology and Infectious Diseases, Nuffield Department of Medicine, University of Oxford, Oxford, UKDepartment of Medical Microbiology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, IndiaDepartment of Medical Microbiology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, IndiaDepartment of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, IndiaDepartment of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, IndiaObjectives: Rapid diagnosis of drug-resistant tuberculosis (TB) is required for better patient management and treatment outcomes. Whole-genome sequencing (WGS) can be used to detect single nucleotide polymorphisms (SNPs) and deletions/insertions that are responsible for mostMycobacterium tuberculosis drug resistance. WGS is being performed at scale in high-income countries, but there are limited reports of its use in India. Methods: In this study, 33 clinicalM. tuberculosis isolates from the Mycobacterial Repository in Chandigarh underwent WGS. Phenotypic drug susceptibility testing was performed according to World Health Organization (WHO) recommendations. Four isolates were excluded from the analysis due to culture contamination or mislabelling during the study. Results: Among the remaining 29 isolates, 21 (72.4%) were multidrug-resistant TB (MDR-TB) and 1 (3.4%) was extensively-drug resistant TB (XDR-TB). The most common mutations observed for isoniazid, rifampicin, ofloxacin and kanamycin resistance werekatG(S315T), rpoB(S450L), gyrA(A90V) and rrs(A1401G), respectively. The isolates mainly belonged to lineages 2 and 3, with most MDR-TB among lineage 2 isolates. Conclusion: WGS ofM. tuberculosis isolates allows the detection of drug resistance to all drugs in a single test and also provides insight into the evolution and drug-resistant TB.http://www.sciencedirect.com/science/article/pii/S2213716519301298Whole-genome sequencingTuberculosisDiagnosisDrug resistanceStrain typing
spellingShingle Sunil Sethi
Yuhan Hao
Stuart M. Brown
Timothy Walker
Rakesh Yadav
Kamran Zaman
Ashutosh Nath Aggarwal
Digambar Behera
Elucidation of drug resistance mutations in Mycobacterium tuberculosis isolates from North India by whole-genome sequencing
Journal of Global Antimicrobial Resistance
Whole-genome sequencing
Tuberculosis
Diagnosis
Drug resistance
Strain typing
title Elucidation of drug resistance mutations in Mycobacterium tuberculosis isolates from North India by whole-genome sequencing
title_full Elucidation of drug resistance mutations in Mycobacterium tuberculosis isolates from North India by whole-genome sequencing
title_fullStr Elucidation of drug resistance mutations in Mycobacterium tuberculosis isolates from North India by whole-genome sequencing
title_full_unstemmed Elucidation of drug resistance mutations in Mycobacterium tuberculosis isolates from North India by whole-genome sequencing
title_short Elucidation of drug resistance mutations in Mycobacterium tuberculosis isolates from North India by whole-genome sequencing
title_sort elucidation of drug resistance mutations in mycobacterium tuberculosis isolates from north india by whole genome sequencing
topic Whole-genome sequencing
Tuberculosis
Diagnosis
Drug resistance
Strain typing
url http://www.sciencedirect.com/science/article/pii/S2213716519301298
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