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
Type
ArticleAuthors
Bergval, IndraColl, Francesc

Schuitema, Anja
de Ronde, Hans
Mallard, Kim
Pain, Arnab

McNerney, Ruth

Clark, Taane G.

Anthony, Richard M.
KAUST Department
Biological and Environmental Sciences and Engineering (BESE) DivisionBioscience Program
Date
2014-12-04Online Publication Date
2014-12-04Print Publication Date
2015-01-01Permanent link to this record
http://hdl.handle.net/10754/622370
Metadata
Show full item recordAbstract
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 LettersPubMed ID
25670707ae974a485f413a2113503eed53cd6c53
10.1093/femsle/fnu037