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    A proportion of mutations fixed in the genomes of in vitro selected isogenic drug-resistant Mycobacterium tuberculosis mutants can be detected as minority variants in the parent culture

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    Type
    Article
    Authors
    Bergval, Indra
    Coll, Francesc cc
    Schuitema, Anja
    de Ronde, Hans
    Mallard, Kim
    Pain, Arnab cc
    McNerney, Ruth cc
    Clark, Taane G. cc
    Anthony, Richard M.
    KAUST Department
    Biological and Environmental Sciences and Engineering (BESE) Division
    Bioscience Program
    Date
    2014-12-04
    Online Publication Date
    2014-12-04
    Print Publication Date
    2015-01-01
    Permanent link to this record
    http://hdl.handle.net/10754/622370
    
    Metadata
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    Abstract
    We studied genomic variation in a previously selected collection of isogenic Mycobacterium tuberculosis laboratory strains subjected to one or two rounds of antibiotic selection. Whole genome sequencing analysis identified eleven single, unique mutations (four synonymous, six non-synonymous, one intergenic), in addition to drug resistance-conferring mutations, that were fixed in the genomes of six monoresistant strains. Eight loci, present as minority variants (five non-synonymous, three synonymous) in the genome of the susceptible parent strain, became fixed in the genomes of multiple daughter strains. None of these mutations are known to be involved with drug resistance. Our results confirm previously observed genomic stability for M. tuberculosis, although the parent strain had accumulated allelic variants at multiple locations in an antibiotic-free in vitro environment. It is therefore likely to assume that these so-called hitchhiking mutations were co-selected and fixed in multiple daughter strains during antibiotic selection. The presence of multiple allelic variations, accumulated under non-selective conditions, which become fixed during subsequent selective steps, deserves attention. The wider availability of 'deep' sequencing methods could help to detect multiple bacterial (sub)populations within patients with high resolution and would therefore be useful in assisting in the detailed investigation of transmission chains.
    Citation
    Bergval I, Coll F, Schuitema A, de Ronde H, Mallard K, et al. (2014) A proportion of mutations fixed in the genomes of in vitro selected isogenic drug-resistant Mycobacterium tuberculosis mutants can be detected as minority variants in the parent culture. FEMS Microbiology Letters 362: 1–7. Available: http://dx.doi.org/10.1093/femsle/fnu037.
    Sponsors
    FC is funded by a Bloomsbury PhD studentship. TC receives funding from the MRC UK (Grant number MR/K000551/1).
    Publisher
    Oxford University Press (OUP)
    Journal
    FEMS Microbiology Letters
    DOI
    10.1093/femsle/fnu037
    PubMed ID
    25670707
    ae974a485f413a2113503eed53cd6c53
    10.1093/femsle/fnu037
    Scopus Count
    Collections
    Articles; Biological and Environmental Science and Engineering (BESE) Division; Bioscience Program

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