Whole-Genome Sequencing to Identify Missed Rifampicin and Isoniazid Resistance Among Tuberculosis Isolates—Chennai, India, 2013–2016

India has a high burden of drug-resistant tuberculosis (DR TB) and many cases go undetected by current drug susceptibility tests (DSTs). This study was conducted to identify rifampicin (RIF) and isoniazid (INH) resistance associated genetic mutations undetected by current clinical diagnostics amongs...

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Autores principales:	Sembulingam Tamilzhalagan, Sivakumar Shanmugam, Ashok Selvaraj, Sakthi Suba, Chittibabu Suganthi, Patrick K. Moonan, Diya Surie, Mukesh Kumar Sathyanarayanan, Narayanan Shivaram Gomathi, Lavanya Jayabal, Kuldeep Singh Sachdeva, Sriram Selvaraju, Soumya Swaminathan, Srikanth Prasad Tripathy, Patricia J. Hall, Uma Devi Ranganathan
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	drug susceptibility testing genetic mutations line probe assay whole genome sequencing DR TB Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/ff71cca09e6948818bf864696a9fed21
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spelling	oai:doaj.org-article:ff71cca09e6948818bf864696a9fed212021-11-22T06:21:32ZWhole-Genome Sequencing to Identify Missed Rifampicin and Isoniazid Resistance Among Tuberculosis Isolates—Chennai, India, 2013–20161664-302X10.3389/fmicb.2021.720436https://doaj.org/article/ff71cca09e6948818bf864696a9fed212021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmicb.2021.720436/fullhttps://doaj.org/toc/1664-302XIndia has a high burden of drug-resistant tuberculosis (DR TB) and many cases go undetected by current drug susceptibility tests (DSTs). This study was conducted to identify rifampicin (RIF) and isoniazid (INH) resistance associated genetic mutations undetected by current clinical diagnostics amongst persons with DR TB in Chennai, India. Retrospectively stored 166 DR TB isolates during 2013–2016 were retrieved and cultured in Löwenstein-Jensen medium. Whole genome sequencing (WGS) and MGIT DST for RIF and INH were performed. Discordant genotypic and phenotypic sensitivity results were repeated for confirmation and the discrepant results considered final. Further, drug resistance-conferring mutations identified through WGS were analyzed for their presence as targets in current WHO-recommended molecular diagnostics. WGS detected additional mutations for rifampicin and isoniazid resistance than WHO-endorsed line probe assays. For RIF, WGS was able to identify an additional 10% (15/146) of rpoB mutant isolates associated with borderline rifampicin resistance compared to MGIT DST. WGS could detect additional DR TB cases than commercially available and WHO-endorsed molecular DST tests. WGS results reiterate the importance of the recent WHO revised critical concentrations of current MGIT DST to detect low-level resistance to rifampicin. WGS may help inform effective treatment selection for persons at risk of, or diagnosed with, DR TB.Sembulingam TamilzhalaganSivakumar ShanmugamAshok SelvarajSakthi SubaChittibabu SuganthiPatrick K. MoonanDiya SurieMukesh Kumar SathyanarayananNarayanan Shivaram GomathiLavanya JayabalKuldeep Singh SachdevaSriram SelvarajuSoumya SwaminathanSoumya SwaminathanSrikanth Prasad TripathyPatricia J. HallUma Devi RanganathanFrontiers Media S.A.articledrug susceptibility testinggenetic mutationsline probe assaywhole genome sequencingDR TBMicrobiologyQR1-502ENFrontiers in Microbiology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	drug susceptibility testing genetic mutations line probe assay whole genome sequencing DR TB Microbiology QR1-502
spellingShingle	drug susceptibility testing genetic mutations line probe assay whole genome sequencing DR TB Microbiology QR1-502 Sembulingam Tamilzhalagan Sivakumar Shanmugam Ashok Selvaraj Sakthi Suba Chittibabu Suganthi Patrick K. Moonan Diya Surie Mukesh Kumar Sathyanarayanan Narayanan Shivaram Gomathi Lavanya Jayabal Kuldeep Singh Sachdeva Sriram Selvaraju Soumya Swaminathan Soumya Swaminathan Srikanth Prasad Tripathy Patricia J. Hall Uma Devi Ranganathan Whole-Genome Sequencing to Identify Missed Rifampicin and Isoniazid Resistance Among Tuberculosis Isolates—Chennai, India, 2013–2016
description	India has a high burden of drug-resistant tuberculosis (DR TB) and many cases go undetected by current drug susceptibility tests (DSTs). This study was conducted to identify rifampicin (RIF) and isoniazid (INH) resistance associated genetic mutations undetected by current clinical diagnostics amongst persons with DR TB in Chennai, India. Retrospectively stored 166 DR TB isolates during 2013–2016 were retrieved and cultured in Löwenstein-Jensen medium. Whole genome sequencing (WGS) and MGIT DST for RIF and INH were performed. Discordant genotypic and phenotypic sensitivity results were repeated for confirmation and the discrepant results considered final. Further, drug resistance-conferring mutations identified through WGS were analyzed for their presence as targets in current WHO-recommended molecular diagnostics. WGS detected additional mutations for rifampicin and isoniazid resistance than WHO-endorsed line probe assays. For RIF, WGS was able to identify an additional 10% (15/146) of rpoB mutant isolates associated with borderline rifampicin resistance compared to MGIT DST. WGS could detect additional DR TB cases than commercially available and WHO-endorsed molecular DST tests. WGS results reiterate the importance of the recent WHO revised critical concentrations of current MGIT DST to detect low-level resistance to rifampicin. WGS may help inform effective treatment selection for persons at risk of, or diagnosed with, DR TB.
format	article
author	Sembulingam Tamilzhalagan Sivakumar Shanmugam Ashok Selvaraj Sakthi Suba Chittibabu Suganthi Patrick K. Moonan Diya Surie Mukesh Kumar Sathyanarayanan Narayanan Shivaram Gomathi Lavanya Jayabal Kuldeep Singh Sachdeva Sriram Selvaraju Soumya Swaminathan Soumya Swaminathan Srikanth Prasad Tripathy Patricia J. Hall Uma Devi Ranganathan
author_facet	Sembulingam Tamilzhalagan Sivakumar Shanmugam Ashok Selvaraj Sakthi Suba Chittibabu Suganthi Patrick K. Moonan Diya Surie Mukesh Kumar Sathyanarayanan Narayanan Shivaram Gomathi Lavanya Jayabal Kuldeep Singh Sachdeva Sriram Selvaraju Soumya Swaminathan Soumya Swaminathan Srikanth Prasad Tripathy Patricia J. Hall Uma Devi Ranganathan
author_sort	Sembulingam Tamilzhalagan
title	Whole-Genome Sequencing to Identify Missed Rifampicin and Isoniazid Resistance Among Tuberculosis Isolates—Chennai, India, 2013–2016
title_short	Whole-Genome Sequencing to Identify Missed Rifampicin and Isoniazid Resistance Among Tuberculosis Isolates—Chennai, India, 2013–2016
title_full	Whole-Genome Sequencing to Identify Missed Rifampicin and Isoniazid Resistance Among Tuberculosis Isolates—Chennai, India, 2013–2016
title_fullStr	Whole-Genome Sequencing to Identify Missed Rifampicin and Isoniazid Resistance Among Tuberculosis Isolates—Chennai, India, 2013–2016
title_full_unstemmed	Whole-Genome Sequencing to Identify Missed Rifampicin and Isoniazid Resistance Among Tuberculosis Isolates—Chennai, India, 2013–2016
title_sort	whole-genome sequencing to identify missed rifampicin and isoniazid resistance among tuberculosis isolates—chennai, india, 2013–2016
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/ff71cca09e6948818bf864696a9fed21
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Whole-Genome Sequencing to Identify Missed Rifampicin and Isoniazid Resistance Among Tuberculosis Isolates—Chennai, India, 2013–2016

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