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U.S.A."],"published-print":{"date-parts":[[2025,9,30]]},"abstract":"<jats:p>\n                    <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                    bacteremia is typically treated empirically with vancomycin, with therapy later tailored based on susceptibility results. However, these tests occur before vancomycin exposure and do not account for adaptation during empiric treatment that can alter\n                    <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                    \u2019 susceptibility to first-line drugs. To investigate these collateral drug responses, we experimentally evolved 18 methicillin-susceptible\n                    <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                    (MSSA) populations under increasing vancomycin concentrations until they achieved intermediate resistance. Genomic sequencing revealed two distinct adaptive pathways characterized by mutations in the WalKR regulon, affecting cell wall metabolism, or\n                    <jats:italic toggle=\"yes\">rpsU<\/jats:italic>\n                    , impacting translational stress responses. These pathways correlated with divergent collateral sensitivity profiles to first-line antibiotics. By developing a Collateral Response Score (CRS), we quantified the probability and magnitude of these responses, demonstrating that evolutionary dynamics critically influence resistance outcomes. Our findings suggest a probabilistic approach to antimicrobial therapy, advocating for rapid genomic diagnostics alongside susceptibility testing to better anticipate and respond to evolutionary changes.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2507962122","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T15:49:21Z","timestamp":1758815361000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":4,"title":["Evolution under vancomycin selection drives divergent collateral sensitivity patterns in\n                    <i>Staphylococcus aureus<\/i>"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0462-2777","authenticated-orcid":false,"given":"Kyle J.","family":"Card","sequence":"first","affiliation":[{"name":"Department of Genomic Medicine, Cleveland Clinic Research","place":["Cleveland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dena","family":"Crozier","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Lerner College of Medicine, Case Western Reserve University","place":["Cleveland"]},{"name":"Department of Medicine, Washington University School of Medicine","place":["St. Louis"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arda","family":"Durmaz","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine, Cleveland Clinic Research","place":["Cleveland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Gray","sequence":"additional","affiliation":[{"name":"Department of Physics, Case Western Reserve University","place":["Cleveland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5426-4224","authenticated-orcid":false,"given":"Justin","family":"Creary","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine, Cleveland Clinic Research","place":["Cleveland"]},{"name":"Department of Biology, Case Western Reserve University","place":["Cleveland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amira","family":"Stocks","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine, Cleveland Clinic Research","place":["Cleveland"]},{"name":"Department of Biology, Case Western Reserve University","place":["Cleveland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff","family":"Maltas","sequence":"additional","affiliation":[{"name":"Department of Physics, Case Western Reserve University","place":["Cleveland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3299-894X","authenticated-orcid":false,"given":"Robert A.","family":"Bonomo","sequence":"additional","affiliation":[{"name":"Medical Service, Louis Stokes Cleveland Department of Veteran Affairs Medical Center","place":["Cleveland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9601-0956","authenticated-orcid":false,"given":"Zachary D. 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