Genetic variation in Mycobacterium tuberculosis isolates from a London outbreak associated with isoniazid resistance
Background:
The largest outbreak of isoniazid-resistant (INH-R) Mycobacterium tuberculosis in Western Europe is centred in North London, with over 400 cases diagnosed since 1995. In the current study, we evaluated the genetic variation in a subset of clinical samples from the outbreak with the hypothesis that these isolates have unique biological characteristics that have served to prolong the outbreak.
Methods:
Fitness assays, mutation rate estimation, and whole-genome sequencing were performed to test for selective advantage and compensatory mutations.
Results:
This detailed analysis of the genetic variation of these INH-R samples suggests that this outbreak consists of successful, closely related, circulating strains with heterogeneous resistance profiles and little or no associated fitness cost or impact on their mutation rate.
Conclusions:
Specific deletions and SNPs could be a peculiar feature of these INH-R M. tuberculosis isolates, and could potentially explain their persistence over the years.
Keywords:
Mycobacterium tuberculosis Whole-genome sequencing Fitness Mutation rate
Autoři:
Giovanni Satta 1,2*; Adam A. Witney 3; Robert J. Shorten 1,4; Magdalena Karlikowska 1; Marc Lipman 5,6; Timothy D. Mchugh 1
Působiště autorů:
Department of Infection, Centre for Clinical Microbiology, University College London, London, UK.
1; Imperial College Healthcare NHS Trust, London, UK.
2; Institute of Infection and Immunity, St George’s, University of London, London, UK.
3; Public Health Laboratory Manchester, Manchester Royal Infirmary, Manchester, UK.
4; Royal Free London NHS Foundation Trust, London, UK. 6UCL Respiratory, Division of Medicine, University College London, London, UK.
5
Vyšlo v časopise:
BMC Medicine 2016, 14:117
Kategorie:
Research article
prolekare.web.journal.doi_sk:
https://doi.org/10.1186/s12916-016-0659-6
© 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
The electronic version of this article is the complete one and can be found online at: https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0659-6
Souhrn
Background:
The largest outbreak of isoniazid-resistant (INH-R) Mycobacterium tuberculosis in Western Europe is centred in North London, with over 400 cases diagnosed since 1995. In the current study, we evaluated the genetic variation in a subset of clinical samples from the outbreak with the hypothesis that these isolates have unique biological characteristics that have served to prolong the outbreak.
Methods:
Fitness assays, mutation rate estimation, and whole-genome sequencing were performed to test for selective advantage and compensatory mutations.
Results:
This detailed analysis of the genetic variation of these INH-R samples suggests that this outbreak consists of successful, closely related, circulating strains with heterogeneous resistance profiles and little or no associated fitness cost or impact on their mutation rate.
Conclusions:
Specific deletions and SNPs could be a peculiar feature of these INH-R M. tuberculosis isolates, and could potentially explain their persistence over the years.
Keywords:
Mycobacterium tuberculosis Whole-genome sequencing Fitness Mutation rate
Zdroje
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