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Whole-genome sequencing of rifampicin-resistant M. tuberculosis strains identifies compensatory mutations in RNA polymerase

Drug-resistant bacteria are emerging worldwide, despite frequently being less fit than drug-susceptible strains(1). Data from model systems suggest the fitness cost of antimicrobial resistance can be mitigated by compensatory mutations(2). However, current evidence that compensatory evolution plays...

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Autores principales: Comas, Iñaki, Borrell, Sonia, Roetzer, Andreas, Rose, Graham, Malla, Bijaya, Kato-Maeda, Midori, Galagan, James, Niemann, Stefan, Gagneux, Sebastien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3246538/
https://www.ncbi.nlm.nih.gov/pubmed/22179134
http://dx.doi.org/10.1038/ng.1038
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author Comas, Iñaki
Borrell, Sonia
Roetzer, Andreas
Rose, Graham
Malla, Bijaya
Kato-Maeda, Midori
Galagan, James
Niemann, Stefan
Gagneux, Sebastien
author_facet Comas, Iñaki
Borrell, Sonia
Roetzer, Andreas
Rose, Graham
Malla, Bijaya
Kato-Maeda, Midori
Galagan, James
Niemann, Stefan
Gagneux, Sebastien
author_sort Comas, Iñaki
collection PubMed
description Drug-resistant bacteria are emerging worldwide, despite frequently being less fit than drug-susceptible strains(1). Data from model systems suggest the fitness cost of antimicrobial resistance can be mitigated by compensatory mutations(2). However, current evidence that compensatory evolution plays any significant role in the success of drug-resistant bacteria in human populations is weak(3–6). Here we describe a set of novel compensatory mutations in the RNA polymerase of rifampicin-resistant Mycobacterium tuberculosis, the etiologic agent of human tuberculosis (TB). M. tuberculosis strains harbouring these compensatory mutations exhibited a high competitive fitness in vitro. Moreover, these mutations were associated with high in vivo fitness as determined by their relative clinical frequency across patient populations. Importantly, in countries with the world’s highest incidence of multidrug-resistant (MDR) TB(7), more than 30% of MDR clinical isolates had such a mutation. Our findings support a role for compensatory evolution in the global epidemics of MDR-TB(8).
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spelling pubmed-32465382012-07-01 Whole-genome sequencing of rifampicin-resistant M. tuberculosis strains identifies compensatory mutations in RNA polymerase Comas, Iñaki Borrell, Sonia Roetzer, Andreas Rose, Graham Malla, Bijaya Kato-Maeda, Midori Galagan, James Niemann, Stefan Gagneux, Sebastien Nat Genet Article Drug-resistant bacteria are emerging worldwide, despite frequently being less fit than drug-susceptible strains(1). Data from model systems suggest the fitness cost of antimicrobial resistance can be mitigated by compensatory mutations(2). However, current evidence that compensatory evolution plays any significant role in the success of drug-resistant bacteria in human populations is weak(3–6). Here we describe a set of novel compensatory mutations in the RNA polymerase of rifampicin-resistant Mycobacterium tuberculosis, the etiologic agent of human tuberculosis (TB). M. tuberculosis strains harbouring these compensatory mutations exhibited a high competitive fitness in vitro. Moreover, these mutations were associated with high in vivo fitness as determined by their relative clinical frequency across patient populations. Importantly, in countries with the world’s highest incidence of multidrug-resistant (MDR) TB(7), more than 30% of MDR clinical isolates had such a mutation. Our findings support a role for compensatory evolution in the global epidemics of MDR-TB(8). 2011-12-18 /pmc/articles/PMC3246538/ /pubmed/22179134 http://dx.doi.org/10.1038/ng.1038 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Comas, Iñaki
Borrell, Sonia
Roetzer, Andreas
Rose, Graham
Malla, Bijaya
Kato-Maeda, Midori
Galagan, James
Niemann, Stefan
Gagneux, Sebastien
Whole-genome sequencing of rifampicin-resistant M. tuberculosis strains identifies compensatory mutations in RNA polymerase
title Whole-genome sequencing of rifampicin-resistant M. tuberculosis strains identifies compensatory mutations in RNA polymerase
title_full Whole-genome sequencing of rifampicin-resistant M. tuberculosis strains identifies compensatory mutations in RNA polymerase
title_fullStr Whole-genome sequencing of rifampicin-resistant M. tuberculosis strains identifies compensatory mutations in RNA polymerase
title_full_unstemmed Whole-genome sequencing of rifampicin-resistant M. tuberculosis strains identifies compensatory mutations in RNA polymerase
title_short Whole-genome sequencing of rifampicin-resistant M. tuberculosis strains identifies compensatory mutations in RNA polymerase
title_sort whole-genome sequencing of rifampicin-resistant m. tuberculosis strains identifies compensatory mutations in rna polymerase
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3246538/
https://www.ncbi.nlm.nih.gov/pubmed/22179134
http://dx.doi.org/10.1038/ng.1038
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