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: 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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