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dc.contributor.authorDarwin J. Operarioen_US
dc.contributor.authorAlexander F. Koeppelen_US
dc.contributor.authorStephen D. Turneren_US
dc.contributor.authorYongde Baoen_US
dc.contributor.authorSuporn Pholwaten_US
dc.contributor.authorSayera Banuen_US
dc.contributor.authorSuporn Foongladdaen_US
dc.contributor.authorStellah Mpagamaen_US
dc.contributor.authorJean Gratzen_US
dc.contributor.authorOleg Ogarkoven_US
dc.contributor.authorSvetlana Zhadovaen_US
dc.contributor.authorScott K. Heysellen_US
dc.contributor.authorEric R. Houpten_US
dc.contributor.otherUniversity of Virginiaen_US
dc.contributor.otherInternational Centre for Diarrhoeal Disease Research Bangladeshen_US
dc.contributor.otherMahidol Universityen_US
dc.contributor.otherKibong'oto Infectious Diseases Hospitalen_US
dc.contributor.otherScientific Сentre for Family Health and Human Reproduction Problemsen_US
dc.identifier.citationPLoS ONE. Vol.12, No.5 (2017)en_US
dc.description.abstract© 2017 Operario et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Amplicon-based Next Generation Sequencing (NGS) is an emerging method for Mycobacterium tuberculosis drug susceptibility testing (DST) but has not been well described. We examined 158 clinical multidrug-resistant M. tuberculosis isolates via NGS of 11 resistance-associated gene regions covering 3519 nucleotides. Across these gene regions, complete resistance or heteroresistance (defined as 1%-99% mutation) was present in at least one isolate in 6.3% of loci. The number of isolates with heteroresistance was highest for gyrA codon 94, rpoB codons 526 and 531, and embB codons 306, 372 and 406 (range 11-26% of isolates exhibited heteroresistance). 57% of MDR strains had heteroresistance of one or more recognized resistance-associated mutation. Heteroresistant loci generally exhibited high or low degrees of mutation (>90% or <10%). The deep sensitivity of NGS for detecting low level pncA heteroresistance appeared to improve genotypic-phenotypic PZA susceptibility correlations over that of Sanger. NGS demonstrates that heteroresistance in TB in the regions of key genes is common and will need to be bioinformatically managed. The clinical significance of such heteroresistance is unclear, and further study of pncA should be pursued.en_US
dc.rightsMahidol Universityen_US
dc.subjectAgricultural and Biological Sciencesen_US
dc.subjectBiochemistry, Genetics and Molecular Biologyen_US
dc.titlePrevalence and extent of heteroresistance by next generation sequencing of multidrug-resistant tuberculosisen_US
Appears in Collections:Scopus 2016-2017

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