Rampant Parasexuality Evolves in a Hospital Pathogen during Antibiotic Selection

dc.citation.firstpage2585en_US
dc.citation.issueNumber10en_US
dc.citation.journalTitleMolecular Biology and Evolutionen_US
dc.citation.lastpage2597en_US
dc.citation.volumeNumber32en_US
dc.contributor.authorBeabout, Kathrynen_US
dc.contributor.authorHammerstrom, Troy G.en_US
dc.contributor.authorWang, Tim T.en_US
dc.contributor.authorBhatty, Minnyen_US
dc.contributor.authorChristie, Peter J.en_US
dc.contributor.authorSaxer, Gerdaen_US
dc.contributor.authorShamoo, Yousifen_US
dc.date.accessioned2015-09-24T18:13:01Zen_US
dc.date.available2015-09-24T18:13:01Zen_US
dc.date.issued2015en_US
dc.description.abstractHorizontal gene transfer threatens the therapeutic success of antibiotics by facilitating the rapid dissemination of resistance alleles among bacterial species. The conjugative mobile element Tn916 provides an excellent context for examining the role of adaptive parasexuality as it carries the tetracycline-resistance allele tetM and has been identified in a wide range of pathogens. We have used a combination of experimental evolution and allelic frequency measurements to gain insights into the adaptive trajectories leading to tigecycline resistance in a hospital strain of Enterococcus faecalis and predict what mechanisms of resistance are most likely to appear in the clinical setting. Here, we show that antibiotic selection led to the near fixation of adaptive alleles that simultaneously altered TetM expression and produced remarkably increased levels of Tn916 horizontal gene transfer. In the absence of drug, approximately 1 in 120,000 of the nonadapted E. faecalis S613 cells had an excised copy of Tn916, whereas nearly 1 in 50 cells had an excised copy of Tn916 upon selection for resistance resulting in a more than 1,000-fold increase in conjugation rates. We also show that tigecycline, a translation inhibitor, selected for a mutation in the ribosomal S10 protein. Our results show the first example of mutations that concurrently confer resistance to an antibiotic and lead to constitutive conjugal-transfer of the resistance allele. Selection created a highly parasexual phenotype and high frequency of Tn916 jumping demonstrating how the use of antibiotics can lead directly to the proliferation of resistance in, and potentially among, pathogens.en_US
dc.identifier.citationBeabout, Kathryn, Hammerstrom, Troy G., Wang, Tim T., et al.. "Rampant Parasexuality Evolves in a Hospital Pathogen during Antibiotic Selection." <i>Molecular Biology and Evolution,</i> 32, no. 10 (2015) Oxford University Press: 2585-2597. http://dx.doi.org/10.1093/molbev/msv133.en_US
dc.identifier.doihttp://dx.doi.org/10.1093/molbev/msv133en_US
dc.identifier.urihttps://hdl.handle.net/1911/81713en_US
dc.language.isoengen_US
dc.publisherOxford University Pressen_US
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher.en_US
dc.subject.keywordhorizontal gene transferen_US
dc.subject.keywordantibiotic resistanceen_US
dc.subject.keywordexperimental evolutionen_US
dc.subject.keywordtigecycline pathogenen_US
dc.subject.keywordEnterococcus faecalisen_US
dc.titleRampant Parasexuality Evolves in a Hospital Pathogen during Antibiotic Selectionen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpost-printen_US
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