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Whole-Genome Sequencing of Mycobacterium tuberculosis Provides Insight into the Evolution and Genetic Composition of Drug-Resistant Tuberculosis in Belarus
The emergence and spread of drug-resistant Mycobacterium tuberculosis (DR-TB) are critical global health issues. Eastern Europe has some of the highest incidences of DR-TB, particularly multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB. To better understand the genetic composition an...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5277515/ https://www.ncbi.nlm.nih.gov/pubmed/27903602 http://dx.doi.org/10.1128/JCM.02116-16 |
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author | Wollenberg, Kurt R. Desjardins, Christopher A. Zalutskaya, Aksana Slodovnikova, Vervara Oler, Andrew J. Quiñones, Mariam Abeel, Thomas Chapman, Sinead B. Tartakovsky, Michael Gabrielian, Andrei Hoffner, Sven Skrahin, Aliaksandr Birren, Bruce W. Rosenthal, Alexander Skrahina, Alena Earl, Ashlee M. |
author_facet | Wollenberg, Kurt R. Desjardins, Christopher A. Zalutskaya, Aksana Slodovnikova, Vervara Oler, Andrew J. Quiñones, Mariam Abeel, Thomas Chapman, Sinead B. Tartakovsky, Michael Gabrielian, Andrei Hoffner, Sven Skrahin, Aliaksandr Birren, Bruce W. Rosenthal, Alexander Skrahina, Alena Earl, Ashlee M. |
author_sort | Wollenberg, Kurt R. |
collection | PubMed |
description | The emergence and spread of drug-resistant Mycobacterium tuberculosis (DR-TB) are critical global health issues. Eastern Europe has some of the highest incidences of DR-TB, particularly multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB. To better understand the genetic composition and evolution of MDR- and XDR-TB in the region, we sequenced and analyzed the genomes of 138 M. tuberculosis isolates from 97 patients sampled between 2010 and 2013 in Minsk, Belarus. MDR and XDR-TB isolates were significantly more likely to belong to the Beijing lineage than to the Euro-American lineage, and known resistance-conferring loci accounted for the majority of phenotypic resistance to first- and second-line drugs in MDR and XDR-TB. Using a phylogenomic approach, we estimated that the majority of MDR-TB was due to the recent transmission of already-resistant M. tuberculosis strains rather than repeated de novo evolution of resistance within patients, while XDR-TB was acquired through both routes. Longitudinal sampling of M. tuberculosis from 34 patients with treatment failure showed that most strains persisted genetically unchanged during treatment or acquired resistance to fluoroquinolones. HIV+ patients were significantly more likely to have multiple infections over time than HIV− patients, highlighting a specific need for careful infection control in these patients. These data provide a better understanding of the genomic composition, transmission, and evolution of MDR- and XDR-TB in Belarus and will enable improved diagnostics, treatment protocols, and prognostic decision-making. |
format | Online Article Text |
id | pubmed-5277515 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-52775152017-02-06 Whole-Genome Sequencing of Mycobacterium tuberculosis Provides Insight into the Evolution and Genetic Composition of Drug-Resistant Tuberculosis in Belarus Wollenberg, Kurt R. Desjardins, Christopher A. Zalutskaya, Aksana Slodovnikova, Vervara Oler, Andrew J. Quiñones, Mariam Abeel, Thomas Chapman, Sinead B. Tartakovsky, Michael Gabrielian, Andrei Hoffner, Sven Skrahin, Aliaksandr Birren, Bruce W. Rosenthal, Alexander Skrahina, Alena Earl, Ashlee M. J Clin Microbiol Mycobacteriology and Aerobic Actinomycetes The emergence and spread of drug-resistant Mycobacterium tuberculosis (DR-TB) are critical global health issues. Eastern Europe has some of the highest incidences of DR-TB, particularly multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB. To better understand the genetic composition and evolution of MDR- and XDR-TB in the region, we sequenced and analyzed the genomes of 138 M. tuberculosis isolates from 97 patients sampled between 2010 and 2013 in Minsk, Belarus. MDR and XDR-TB isolates were significantly more likely to belong to the Beijing lineage than to the Euro-American lineage, and known resistance-conferring loci accounted for the majority of phenotypic resistance to first- and second-line drugs in MDR and XDR-TB. Using a phylogenomic approach, we estimated that the majority of MDR-TB was due to the recent transmission of already-resistant M. tuberculosis strains rather than repeated de novo evolution of resistance within patients, while XDR-TB was acquired through both routes. Longitudinal sampling of M. tuberculosis from 34 patients with treatment failure showed that most strains persisted genetically unchanged during treatment or acquired resistance to fluoroquinolones. HIV+ patients were significantly more likely to have multiple infections over time than HIV− patients, highlighting a specific need for careful infection control in these patients. These data provide a better understanding of the genomic composition, transmission, and evolution of MDR- and XDR-TB in Belarus and will enable improved diagnostics, treatment protocols, and prognostic decision-making. American Society for Microbiology 2017-01-25 2017-02 /pmc/articles/PMC5277515/ /pubmed/27903602 http://dx.doi.org/10.1128/JCM.02116-16 Text en Copyright © 2017 Wollenberg et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Mycobacteriology and Aerobic Actinomycetes Wollenberg, Kurt R. Desjardins, Christopher A. Zalutskaya, Aksana Slodovnikova, Vervara Oler, Andrew J. Quiñones, Mariam Abeel, Thomas Chapman, Sinead B. Tartakovsky, Michael Gabrielian, Andrei Hoffner, Sven Skrahin, Aliaksandr Birren, Bruce W. Rosenthal, Alexander Skrahina, Alena Earl, Ashlee M. Whole-Genome Sequencing of Mycobacterium tuberculosis Provides Insight into the Evolution and Genetic Composition of Drug-Resistant Tuberculosis in Belarus |
title | Whole-Genome Sequencing of Mycobacterium tuberculosis Provides Insight into the Evolution and Genetic Composition of Drug-Resistant Tuberculosis in Belarus |
title_full | Whole-Genome Sequencing of Mycobacterium tuberculosis Provides Insight into the Evolution and Genetic Composition of Drug-Resistant Tuberculosis in Belarus |
title_fullStr | Whole-Genome Sequencing of Mycobacterium tuberculosis Provides Insight into the Evolution and Genetic Composition of Drug-Resistant Tuberculosis in Belarus |
title_full_unstemmed | Whole-Genome Sequencing of Mycobacterium tuberculosis Provides Insight into the Evolution and Genetic Composition of Drug-Resistant Tuberculosis in Belarus |
title_short | Whole-Genome Sequencing of Mycobacterium tuberculosis Provides Insight into the Evolution and Genetic Composition of Drug-Resistant Tuberculosis in Belarus |
title_sort | whole-genome sequencing of mycobacterium tuberculosis provides insight into the evolution and genetic composition of drug-resistant tuberculosis in belarus |
topic | Mycobacteriology and Aerobic Actinomycetes |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5277515/ https://www.ncbi.nlm.nih.gov/pubmed/27903602 http://dx.doi.org/10.1128/JCM.02116-16 |
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