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Genetic variation in Mycobacterium tuberculosis isolates from a London outbreak associated with isoniazid resistance.

Satta, G; Witney, AA; Shorten, RJ; Karlikowska, M; Lipman, M; McHugh, TD (2016) Genetic variation in Mycobacterium tuberculosis isolates from a London outbreak associated with isoniazid resistance. BMC Medicine, 14 (1 : 117). https://doi.org/10.1186/s12916-016-0659-6
SGUL Authors: Witney, Adam Austin

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Abstract

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.

Item Type: Article
Additional Information: © 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.
Keywords: Fitness, Mutation rate, Mycobacterium tuberculosis, Whole-genome sequencing, Fitness, Mutation rate, Mycobacterium tuberculosis, Whole-genome sequencing, General & Internal Medicine, 11 Medical And Health Sciences
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: BMC Medicine
Language: eng
Dates:
DateEvent
16 August 2016Published Online
16 August 2016Published
26 July 2016Accepted
Publisher License: Creative Commons: Attribution 4.0
PubMed ID: 27530812
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/108205
Publisher's version: https://doi.org/10.1186/s12916-016-0659-6

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