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

BMC Medicine

Research Article

Magdalena Karlikowska¹  Timothy D. McHugh¹  Giovanni Satta²  Robert J. Shorten³  Adam A. Witney⁴  Marc Lipman⁵ 

[1] Department of Infection, Centre for Clinical Microbiology, University College London, London, UK;Department of Infection, Centre for Clinical Microbiology, University College London, London, UK;Imperial College Healthcare NHS Trust, London, UK;Department of Infection, Centre for Clinical Microbiology, University College London, London, UK;Public Health Laboratory Manchester, Manchester Royal Infirmary, Manchester, UK;Institute of Infection and Immunity, St George’s, University of London, London, UK;Royal Free London NHS Foundation Trust, London, UK;UCL Respiratory, Division of Medicine, University College London, London, UK;

关键词: Mycobacterium tuberculosis;    Whole-genome sequencing;    Fitness;    Mutation rate;   

DOI  :  10.1186/s12916-016-0659-6

 received in 2016-05-11, accepted in 2016-07-26,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundThe 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.MethodsFitness assays, mutation rate estimation, and whole-genome sequencing were performed to test for selective advantage and compensatory mutations.ResultsThis 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.ConclusionsSpecific deletions and SNPs could be a peculiar feature of these INH-R M. tuberculosis isolates, and could potentially explain their persistence over the years.

【 授权许可】

CC BY   
© The Author(s). 2016