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Evolution experiments of\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    rely on growth-dependent selection, which may provide a limited view of the antibiotic resistance landscape. We sequenced and analyzed\n                    <jats:italic>E. coli<\/jats:italic>\n                    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 &gt;3500 clinical\n                    <jats:italic>E. coli<\/jats:italic>\n                    pathogens, indicating clinical relevance.\n                  <\/jats:p>","DOI":"10.1126\/science.aba0862","type":"journal-article","created":{"date-parts":[[2021,2,19]],"date-time":"2021-02-19T13:51:42Z","timestamp":1613742702000},"source":"Crossref","is-referenced-by-count":370,"title":["Clinically relevant mutations in core metabolic genes confer antibiotic resistance"],"prefix":"10.1126","volume":"371","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0018-9205","authenticated-orcid":true,"given":"Allison J.","family":"Lopatkin","sequence":"first","affiliation":[{"name":"Institute for Medical Engineering and Science and Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA."},{"name":"Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA."},{"name":"Wyss Institute for Biologically Inspired Engineering; Harvard University, Boston, MA, USA."},{"name":"Department of Biology, Barnard College, New York, NY, USA."},{"name":"Data Science Institute, Columbia University, New York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7449-3184","authenticated-orcid":true,"given":"Sarah C.","family":"Bening","sequence":"additional","affiliation":[{"name":"Institute for Medical Engineering and Science and Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA."},{"name":"Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3800-0714","authenticated-orcid":true,"given":"Abigail L.","family":"Manson","sequence":"additional","affiliation":[{"name":"Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan M.","family":"Stokes","sequence":"additional","affiliation":[{"name":"Institute for Medical Engineering and Science and Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA."},{"name":"Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA."},{"name":"Wyss Institute for Biologically Inspired Engineering; Harvard University, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8399-364X","authenticated-orcid":true,"given":"Michael A.","family":"Kohanski","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Division of Rhinology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8105-1883","authenticated-orcid":true,"given":"Ahmed H.","family":"Badran","sequence":"additional","affiliation":[{"name":"Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7857-9145","authenticated-orcid":true,"given":"Ashlee M.","family":"Earl","sequence":"additional","affiliation":[{"name":"Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3937-8310","authenticated-orcid":true,"given":"Nicole J.","family":"Cheney","sequence":"additional","affiliation":[{"name":"Ruy V. Louren\u00e7o Center for Emerging and Re-Emerging Pathogens, Rutgers New Jersey Medical School, Newark, NJ, USA."},{"name":"Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0921-4657","authenticated-orcid":true,"given":"Jason H.","family":"Yang","sequence":"additional","affiliation":[{"name":"Ruy V. Louren\u00e7o Center for Emerging and Re-Emerging Pathogens, Rutgers New Jersey Medical School, Newark, NJ, USA."},{"name":"Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5560-8246","authenticated-orcid":true,"given":"James J.","family":"Collins","sequence":"additional","affiliation":[{"name":"Institute for Medical Engineering and Science and Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA."},{"name":"Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA."},{"name":"Wyss Institute for Biologically Inspired Engineering; Harvard University, Boston, MA, USA."},{"name":"Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA, USA."},{"name":"Harvard-MIT Program in Health Sciences and Technology, Cambridge, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_3_2_2","first-page":"137","article-title":"Antibiotic resistance mechanisms of clinically important bacteria","volume":"47","author":"Giedraitien\u0117 A.","year":"2011","unstructured":"A. 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