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dc.contributor.authorLopatkin, Allison J.
dc.contributor.authorBening, Sarah C.
dc.contributor.authorManson, Abigail L.
dc.contributor.authorStokes, Jonathan M.
dc.contributor.authorKohanski, Michael A.
dc.contributor.authorBadran, Ahmed H.
dc.contributor.authorEarl, Ashlee M.
dc.contributor.authorCheney, Nicole J.
dc.contributor.authorYang, Jason H.
dc.contributor.authorCollins, James J.
dc.date.accessioned2022-05-18T15:28:29Z
dc.date.available2021-10-27T19:53:09Z
dc.date.available2022-05-18T15:28:29Z
dc.date.issued2021-02
dc.date.submitted2019-11
dc.identifier.issn0036-8075
dc.identifier.issn1095-9203
dc.identifier.urihttps://hdl.handle.net/1721.1/133494.2
dc.description.abstract© 2021 American Association for the Advancement of Science. All rights reserved. Although metabolism plays an active role in antibiotic lethality, antibiotic resistance is generally associated with drug target modification, enzymatic inactivation, and/or transport rather than metabolic processes. Evolution experiments of Escherichia coli rely on growth-dependent selection, which may provide a limited view of the antibiotic resistance landscape. We sequenced and analyzed E. coli adapted to representative antibiotics at increasingly heightened metabolic states. This revealed various underappreciated noncanonical genes, such as those related to central carbon and energy metabolism, which are implicated in antibiotic resistance. These metabolic alterations lead to lower basal respiration, which prevents antibiotic-mediated induction of tricarboxylic acid cycle activity, thus avoiding metabolic toxicity and minimizing drug lethality. Several of the identified metabolism-specific mutations are overrepresented in the genomes of >3500 clinical E. coli pathogens, indicating clinical relevance.en_US
dc.language.isoen
dc.publisherAmerican Association for the Advancement of Science (AAAS)en_US
dc.relation.isversionofhttp://dx.doi.org/10.1126/science.aba0862en_US
dc.rightsCreative Commons Attribution 4.0 International licenseen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.sourcePMCen_US
dc.titleClinically relevant mutations in core metabolic genes confer antibiotic resistanceen_US
dc.typeArticleen_US
dc.contributor.departmentMassachusetts Institute of Technology. Institute for Medical Engineering & Science
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineering
dc.contributor.departmentHarvard University--MIT Division of Health Sciences and Technology
dc.contributor.departmentMassachusetts Institute of Technology. Institute for Medical Engineering & Science
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineering
dc.contributor.departmentMassachusetts Institute of Technology. Synthetic Biology Center
dc.contributor.departmentHarvard University--MIT Division of Health Sciences and Technology
dc.relation.journalScienceen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2021-08-25T18:29:52Z
dspace.orderedauthorsLopatkin, AJ; Bening, SC; Manson, AL; Stokes, JM; Kohanski, MA; Badran, AH; Earl, AM; Cheney, NJ; Yang, JH; Collins, JJen_US
dspace.date.submission2021-08-25T18:29:53Z
mit.journal.volume371en_US
mit.journal.issue6531en_US
mit.licenseOPEN_ACCESS_POLICY
mit.metadata.statusAuthority Work Neededen_US


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