Acinetobacter baumanniiļ¾  Repeatedly Evolves a Hypermutator Phenotype in Response to Tigecycline That Effectively Surveys Evolutionary Trajectories to Resistance

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dc.citation.firstpagee0140489en_US
dc.citation.issueNumber10en_US
dc.citation.journalTitlePLoS ONEen_US
dc.citation.volumeNumber10en_US
dc.contributor.authorHammerstrom, Troy G.en_US
dc.contributor.authorBeabout, Kathrynen_US
dc.contributor.authorClements, Thomas P.en_US
dc.contributor.authorSaxer, Gerdaen_US
dc.contributor.authorShamoo, Yousifen_US
dc.date.accessioned2016-04-01T20:24:37Zen_US
dc.date.available2016-04-01T20:24:37Zen_US
dc.date.issued2015en_US
dc.description.abstractThe evolution of hypermutators in response to antibiotic treatment in both clinical and laboratory settings provides a unique context for the study of adaptive evolution. With increased mutation rates, the number of hitchhiker mutations within an evolving hypermutator population is remarkably high and presents substantial challenges in determining which mutations are adaptive. Intriguingly however, hypermutators also provide an opportunity to explore deeply the accessible evolutionary trajectories that lead to increased organism fitness, in this case the evolution of antibiotic resistance to the clinically relevant antibiotic tigecycline by the hospital pathogen Acinetobacter baumannii. Using a continuous culture system, AB210M, a clinically derived strain of A. baumannii, was evolved to tigecycline resistance. Analysis of the adapted populations showed that nearly all the successful lineages became hypermutators via movement of a mobile element to inactivate mutS. In addition, metagenomic analysis of population samples revealed another 896 mutations that occurred at a frequency greater than 5% in the population, while 38 phenotypically distinct individual colonies harbored a total of 1712 mutations. These mutations were scattered throughout the genome and affected ~40% of the coding sequences. The most highly mutated gene wasadeS, a known tigecycline-resistance gene; however, adeS was not solely responsible for the high level of TGC resistance. Sixteen other genes stood out as potentially relevant to increased resistance. The five most prominent candidate genes (adeS, rpsJ, rrf, msbA, andgna) consistently re-emerged in subsequent replicate population studies suggesting they are likely to play a role in adaptation to tigecycline. Interestingly, the repeated evolution of a hypermutator phenotype in response to antibiotic stress illustrates not only a highly adaptive strategy to resistance, but also a remarkably efficient survey of successful evolutionary trajectories.en_US
dc.identifier.citationHammerstrom, Troy G., Beabout, Kathryn, Clements, Thomas P., et al.. "Acinetobacter baumanniiļ¾  Repeatedly Evolves a Hypermutator Phenotype in Response to Tigecycline That Effectively Surveys Evolutionary Trajectories to Resistance." <i>PLoS ONE,</i> 10, no. 10 (2015) Public Library of Science: e0140489. http://dx.doi.org/10.1371/journal.pone.0140489.en_US
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pone.0140489en_US
dc.identifier.urihttps://hdl.handle.net/1911/88826en_US
dc.language.isoengen_US
dc.publisherPublic Library of Scienceen_US
dc.rightsThis is an open access article distributed under the terms of theļ¾ Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are crediteden_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.titleAcinetobacter baumanniiļ¾  Repeatedly Evolves a Hypermutator Phenotype in Response to Tigecycline That Effectively Surveys Evolutionary Trajectories to Resistanceen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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