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While acquisition of the\n                    <jats:italic>mec<\/jats:italic>\n                    gene represents the main resistance mechanism to oxacillin,\n                    <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n                    can acquire low-level resistance through adaptive mutations in other genes. In this study, we used genomic approaches to understand the basis of\n                    <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n                    adaption to oxacillin and its dynamic at the population level. By combining a genome analysis of clinical isolates from persistent MSSA infections,\n                    <jats:italic>in vitro<\/jats:italic>\n                    selection of oxacillin resistance, and genome-wide association analysis on a large collection of isolates, we identified 21 genes linked to secondary oxacillin resistance. Adaptive mutations in these genes were easy to select when\n                    <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n                    was exposed to oxacillin, but they also came at a substantial cost in terms of bacterial fitness, suggesting that this phenotype emerges preferentially in the setting of sustained antibiotic exposure.\n                  <\/jats:p>","DOI":"10.1128\/mbio.02882-20","type":"journal-article","created":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T11:59:06Z","timestamp":1607342346000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":53,"title":["Comprehensive Genomic Investigation of Adaptive Mutations Driving the Low-Level Oxacillin Resistance Phenotype in Staphylococcus aureus"],"prefix":"10.1128","volume":"11","author":[{"given":"Stefano G.","family":"Giulieri","sequence":"first","affiliation":[{"name":"Department of Microbiology and 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