dc.citation.firstpage	2585
dc.citation.issueNumber	10
dc.citation.journalTitle	Molecular Biology and Evolution
dc.citation.lastpage	2597
dc.citation.volumeNumber	32
dc.contributor.author	Beabout, Kathryn
dc.contributor.author	Hammerstrom, Troy G.
dc.contributor.author	Wang, Tim T.
dc.contributor.author	Bhatty, Minny
dc.contributor.author	Christie, Peter J.
dc.contributor.author	Saxer, Gerda
dc.contributor.author	Shamoo, Yousif
dc.date.accessioned	2015-09-24T18:13:01Z
dc.date.available	2015-09-24T18:13:01Z
dc.date.issued	2015
dc.description.abstract	Horizontal 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.
dc.identifier.citation	Beabout, 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.
dc.identifier.doi	http://dx.doi.org/10.1093/molbev/msv133
dc.identifier.uri	https://hdl.handle.net/1911/81713
dc.language.iso	eng
dc.publisher	Oxford University Press
dc.rights	This is an author's peer-reviewed final manuscript, as accepted by the publisher.
dc.subject.keyword	horizontal gene transfer
dc.subject.keyword	antibiotic resistance
dc.subject.keyword	experimental evolution
dc.subject.keyword	tigecycline pathogen
dc.subject.keyword	Enterococcus faecalis
dc.title	Rampant Parasexuality Evolves in a Hospital Pathogen during Antibiotic Selection
dc.type	Journal article
dc.type.dcmi	Text
dc.type.publication	post-print

Rampant Parasexuality Evolves in a Hospital Pathogen during Antibiotic Selection

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