{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T08:17:31Z","timestamp":1790324251041,"version":"4.1.0"},"reference-count":35,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T00:00:00Z","timestamp":1448928000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            \u03b2-Lactam resistance in methicillin-resistant\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            (MRSA) is mediated by the expression of an alternative penicillin-binding protein 2a (PBP2a) (encoded by\n            <jats:italic>mecA<\/jats:italic>\n            ) with a low affinity for \u03b2-lactam antibiotics. Recently, a novel variant of\n            <jats:italic>mecA<\/jats:italic>\n            , known as\n            <jats:italic>mecC<\/jats:italic>\n            , was identified in MRSA isolates from both humans and animals. In this study, we demonstrate that\n            <jats:italic>mecC<\/jats:italic>\n            -encoded PBP2c does not mediate resistance to penicillin. Rather, broad-spectrum \u03b2-lactam resistance in MRSA strains carrying\n            <jats:italic>mecC<\/jats:italic>\n            (\n            <jats:italic>mecC<\/jats:italic>\n            -MRSA strains) is mediated by a combination of both PBP2c and the distinct \u03b2-lactamase encoded by the\n            <jats:italic>blaZ<\/jats:italic>\n            gene of strain LGA251 (\n            <jats:italic>blaZ<\/jats:italic>\n            <jats:sub>LGA251<\/jats:sub>\n            ), which is part of\n            <jats:italic>mecC<\/jats:italic>\n            -encoding staphylococcal cassette chromosome\n            <jats:italic>mec<\/jats:italic>\n            (SCC\n            <jats:italic>mec<\/jats:italic>\n            ) type XI. We further demonstrate that\n            <jats:italic>mecC<\/jats:italic>\n            -MRSA strains are susceptible to the combination of penicillin and the \u03b2-lactam inhibitor clavulanic acid\n            <jats:italic>in vitro<\/jats:italic>\n            and that the same combination is effective\n            <jats:italic>in vivo<\/jats:italic>\n            for the treatment of experimental\n            <jats:italic>mecC<\/jats:italic>\n            -MRSA infection in wax moth larvae. Thus, we demonstrate how the distinct biological differences between\n            <jats:italic>mecA<\/jats:italic>\n            - and\n            <jats:italic>mecC<\/jats:italic>\n            -encoded PBP2a and PBP2c have the potential to be exploited as a novel approach for the treatment of\n            <jats:italic>mecC<\/jats:italic>\n            -MRSA infections.\n          <\/jats:p>","DOI":"10.1128\/aac.01469-15","type":"journal-article","created":{"date-parts":[[2015,9,22]],"date-time":"2015-09-22T02:23:49Z","timestamp":1442888629000},"page":"7396-7404","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":42,"title":["Old Drugs To Treat Resistant Bugs: Methicillin-Resistant Staphylococcus aureus Isolates with\n            <i>mecC<\/i>\n            Are Susceptible to a Combination of Penicillin and Clavulanic Acid"],"prefix":"10.1128","volume":"59","author":[{"given":"Xiaoliang","family":"Ba","sequence":"first","affiliation":[{"name":"Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2720-0507","authenticated-orcid":false,"given":"Ewan M.","family":"Harrison","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew L.","family":"Lovering","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Infection and School of Biosciences, University of Birmingham, Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Gleadall","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Zadoks","sequence":"additional","affiliation":[{"name":"Moredun Research Institute, Penicuik, United Kingdom"},{"name":"Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, Glasgow, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7069-5958","authenticated-orcid":false,"given":"Julian","family":"Parkhill","sequence":"additional","affiliation":[{"name":"Wellcome Trust Sanger Institute, Hinxton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon J.","family":"Peacock","sequence":"additional","affiliation":[{"name":"Wellcome Trust Sanger Institute, Hinxton, United Kingdom"},{"name":"University of Cambridge, Department of Medicine, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew T. G.","family":"Holden","sequence":"additional","affiliation":[{"name":"University of St. Andrews, School of Medicine, St. Andrews, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin K.","family":"Paterson","sequence":"additional","affiliation":[{"name":"University of Hull, School of Biological, Biomedical and Environmental Sciences, Hull, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Holmes","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003592"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.99.2579.452"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.5219.124-a"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-060614-034516"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(11)70126-8"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2013.11.003"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02731-13"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.395962"},{"key":"e_1_3_3_10_2","volume-title":"BSAC methods for antimicrobial susceptibility testing, version 13","author":"British Society for Antimicrobial Chemotherapy","year":"2014","unstructured":"British Society for Antimicrobial Chemotherapy. 2014. 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