{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T21:49:52Z","timestamp":1792705792208,"version":"4.5.0"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2016,7,1]],"date-time":"2016-07-01T00:00:00Z","timestamp":1467331200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01-AI100291"],"award-info":[{"award-number":["R01-AI100291"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Staphylococcus aureus<\/jats:named-content>\n            is an important cause of both hospital- and community-associated methicillin-resistant\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus<\/jats:named-content>\n            (MRSA) infections worldwide. \u03b2-Lactam antibiotics are the drugs of choice to treat\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus<\/jats:named-content>\n            infections, but resistance to these and other antibiotics make treatment problematic. High-level \u03b2-lactam resistance of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus<\/jats:named-content>\n            has always been attributed to the horizontally acquired penicillin binding protein 2a (PBP 2a) encoded by the\n            <jats:italic>mecA<\/jats:italic>\n            gene. Here, we show that\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus<\/jats:named-content>\n            can also express high-level resistance to \u03b2-lactams, including new-generation broad-spectrum cephalosporins that are active against methicillin-resistant strains, through an uncanonical core genome-encoded penicillin binding protein, PBP 4, a nonessential enzyme previously considered not to be important for staphylococcal \u03b2-lactam resistance. Our results show that PBP 4 can mediate high-level resistance to \u03b2-lactams.\n          <\/jats:p>","DOI":"10.1128\/aac.00358-16","type":"journal-article","created":{"date-parts":[[2016,4,12]],"date-time":"2016-04-12T03:39:01Z","timestamp":1460432341000},"page":"3934-3941","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":42,"title":["PBP 4 Mediates High-Level Resistance to New-Generation Cephalosporins in Staphylococcus aureus"],"prefix":"10.1128","volume":"60","author":[{"given":"Liana C.","family":"Chan","sequence":"first","affiliation":[{"name":"Division of Infectious Disease, Department of Medicine, San Francisco General Hospital, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aubre","family":"Gilbert","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Medicine, San Francisco General Hospital, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Basuino","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Medicine, San Francisco General Hospital, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thaina M.","family":"da Costa","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Medicine, San Francisco General Hospital, San Francisco, California, USA"},{"name":"Instituto de Microbiologia Paulo de G\u00f3es, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie M.","family":"Hamilton","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Medicine, San Francisco General Hospital, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia R.","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Instituto de Microbiologia Paulo de G\u00f3es, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry F.","family":"Chambers","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Medicine, San Francisco General Hospital, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Som S.","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Medicine, San Francisco General Hospital, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2200"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.2147\/CLEP.S37071"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199808203390806"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.20506\/rst.31.1.2096"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1526-9523(02)00330-6"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2014.09.012"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2006.00024.x"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2008.00105.x"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2007.00095.x"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s000180050023"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1809.111920"},{"key":"e_1_3_3_13_2","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.1111\/j.1469-0691.2006.01403.x","article-title":"Can \u03b2-lactams be re-engineered to beat MRSA?","volume":"12","author":"Livermore DM","year":"2006","unstructured":"Livermore DM. 2006. 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