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dc.date.accessioned2015-02-18T12:04:59Z
dc.date.available2015-02-18T12:04:59Z
dc.date.created2015-01-14T09:31:29Z
dc.date.issued2014
dc.identifier.citationEldholm, Vegard Norheim, Gunnstein Lippe, Bent von der Kinander, Wibeke Dahle, Ulf R Caugant, Dominique A Mannsåker, Turid MENGSHOEL, ANNE TORUNN Dyrhol-Riise, Anne Ma Balloux, Francois . Evolution of extensively drug-resistant Mycobacterium tuberculosis from a susceptible ancestor in a single patient. Genome Biology. 2014, 15(11)
dc.identifier.urihttp://hdl.handle.net/10852/42395
dc.description.abstractBackground Mycobacterium tuberculosis is characterized by a low mutation rate and a lack of genetic recombination. Yet, the rise of extensively resistant strains paints a picture of a microbe with an impressive adaptive potential. Here we describe the first documented case of extensively drug-resistant tuberculosis evolved from a susceptible ancestor within a single patient. Results Genome sequences of nine serial M. tuberculosis isolates from the same patient uncovered a dramatic turnover of competing lineages driven by the emergence, and subsequent fixation or loss of single nucleotide polymorphisms. For most drugs, resistance arose through independent emergence of mutations in more than one clone, of which only one ultimately prevailed as the clone carrying it expanded, displacing the other clones in the process. The vast majority of mutations identified over 3.5 years were either involved in drug resistance or hitchhiking in the genetic background of these. Additionally, RNA-sequencing of isolates grown in the absence of drug challenge revealed that the efflux-associated iniBAC operon was up-regulated over time, whereas down-regulated genes include those involved in mycolic acid synthesis. Conclusions We observed both rapid acquisitions of resistance to antimicrobial compounds mediated by individual mutations as well as a gradual increase in fitness in the presence of antibiotics, likely driven by stable gene expression reprogramming. The rapid turnover of resistance mutations and hitchhiking neutral mutations has major implications for inferring tuberculosis transmission events in situations where drug resistance evolves within transmission chains.en_US
dc.languageEN
dc.language.isoenen_US
dc.publisherBioMed Central
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleEvolution of extensively drug-resistant Mycobacterium tuberculosis from a susceptible ancestor in a single patienten_US
dc.typeJournal articleen_US
dc.creator.authorEldholm, Vegard
dc.creator.authorNorheim, Gunnstein
dc.creator.authorLippe, Bent von der
dc.creator.authorKinander, Wibeke
dc.creator.authorDahle, Ulf R
dc.creator.authorCaugant, Dominique A
dc.creator.authorMannsåker, Turid
dc.creator.authorMENGSHOEL, ANNE TORUNN
dc.creator.authorDyrhol-Riise, Anne Ma
dc.creator.authorBalloux, Francois
cristin.unitcode185,53,11,14
cristin.unitnameInfeksjonsmedisinsk avdeling
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1
dc.identifier.cristin1197258
dc.identifier.bibliographiccitationinfo:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Genome Biology&rft.volume=15&rft.spage=&rft.date=2014
dc.identifier.jtitleGenome Biology
dc.identifier.volume15
dc.identifier.doihttp://dx.doi.org/10.1186/s13059-014-0490-3
dc.identifier.urnURN:NBN:no-46769
dc.subject.nviVDP::Medisinsk mikrobiologi: 715
dc.type.documentTidsskriftartikkelen_US
dc.type.peerreviewedPeer reviewed
dc.source.issn1465-6914
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/42395/2/Eldholm_2014_Evo.pdf
dc.type.versionPublishedVersion
cristin.articleid490


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