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dc.contributor.authorGomez, James Een_US
dc.contributor.authorKaufmann-Malaga, Benjamin Ben_US
dc.contributor.authorWivagg, Carl Nen_US
dc.contributor.authorKim, Peter Ben_US
dc.contributor.authorSilvis, Melanie Ren_US
dc.contributor.authorRenedo, Nikolaien_US
dc.contributor.authorIoerger, Thomas Ren_US
dc.contributor.authorAhmad, Rushdyen_US
dc.contributor.authorLivny, Jonathanen_US
dc.contributor.authorFishbein, Skyeen_US
dc.contributor.authorSacchettini, James Cen_US
dc.contributor.authorCarr, Steven Aen_US
dc.contributor.authorHung, Deborah Ten_US
dc.date.accessioned2017-03-28T23:51:43Z
dc.date.issued2017en_US
dc.identifier.citationGomez, J. E., B. B. Kaufmann-Malaga, C. N. Wivagg, P. B. Kim, M. R. Silvis, N. Renedo, T. R. Ioerger, et al. 2017. “Ribosomal mutations promote the evolution of antibiotic resistance in a multidrug environment.” eLife 6 (1): e20420. doi:10.7554/eLife.20420. http://dx.doi.org/10.7554/eLife.20420.en
dc.identifier.issnen
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:31731855
dc.description.abstractAntibiotic resistance arising via chromosomal mutations is typically specific to a particular antibiotic or class of antibiotics. We have identified mutations in genes encoding ribosomal components in Mycobacterium smegmatis that confer resistance to several structurally and mechanistically unrelated classes of antibiotics and enhance survival following heat shock and membrane stress. These mutations affect ribosome assembly and cause large-scale transcriptomic and proteomic changes, including the downregulation of the catalase KatG, an activating enzyme required for isoniazid sensitivity, and upregulation of WhiB7, a transcription factor involved in innate antibiotic resistance. Importantly, while these ribosomal mutations have a fitness cost in antibiotic-free medium, in a multidrug environment they promote the evolution of high-level, target-based resistance. Further, suppressor mutations can then be easily acquired to restore wild-type growth. Thus, ribosomal mutations can serve as stepping-stones in an evolutionary path leading to the emergence of high-level, multidrug resistance. DOI: http://dx.doi.org/10.7554/eLife.20420.001en
dc.language.isoen_USen
dc.publishereLife Sciences Publications, Ltden
dc.relation.isversionofdoi:10.7554/eLife.20420en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5319836/pdf/en
dash.licenseLAAen_US
dc.subjectMycobacteriumen
dc.subjectantibiotic resistanceen
dc.subjectribosomeen
dc.subjectfluoroquinolonesen
dc.subjectOtheren
dc.titleRibosomal mutations promote the evolution of antibiotic resistance in a multidrug environmenten
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journaleLifeen
dash.depositing.authorGomez, James Een_US
dc.date.available2017-03-28T23:51:43Z
dc.identifier.doi10.7554/eLife.20420*
dash.authorsorderedfalse
dash.contributor.affiliatedFishbein, Skye
dash.contributor.affiliatedWivagg, Carl N
dash.contributor.affiliatedGomez, James
dash.contributor.affiliatedHung, Deborah


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