{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T13:07:43Z","timestamp":1791724063120,"version":"4.3.4"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2017,9,1]],"date-time":"2017-09-01T00:00:00Z","timestamp":1504224000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001590","name":"Health Research Board","doi-asserted-by":"publisher","award":["HRA-POR-2015-1158"],"award-info":[{"award-number":["HRA-POR-2015-1158"]}],"id":[{"id":"10.13039\/501100001590","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010414","name":"Health Research Board","doi-asserted-by":"publisher","award":["HRA-POR-2012-51"],"award-info":[{"award-number":["HRA-POR-2012-51"]}],"id":[{"id":"10.13039\/100010414","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":[[2017,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Hospital-associated methicillin-resistant\n            <jats:named-content content-type=\"genus-species\">Staphylococcus aureus<\/jats:named-content>\n            (MRSA) strains typically express high-level, homogeneous (HoR) \u03b2-lactam resistance, whereas community-associated MRSA (CA-MRSA) more commonly express low-level heterogeneous (HeR) resistance. Expression of the HoR phenotype typically requires both increased expression of the\n            <jats:italic>mecA<\/jats:italic>\n            gene, carried on the staphylococcal cassette chromosome\n            <jats:italic>mec<\/jats:italic>\n            element (SCC\n            <jats:italic>mec<\/jats:italic>\n            ), and additional mutational event(s) elsewhere on the chromosome. Here the oxacillin concentration in a chemostat culture of the CA-MRSA strain USA300 was increased from 8 \u03bcg\/ml to 130 \u03bcg\/ml over 13 days to isolate highly oxacillin-resistant derivatives. A stable, small-colony variant, designated HoR34, which had become established in the chemostat culture was found to have acquired mutations in\n            <jats:italic>gdpP<\/jats:italic>\n            ,\n            <jats:italic>clpX<\/jats:italic>\n            ,\n            <jats:italic>guaA<\/jats:italic>\n            , and\n            <jats:italic>camS<\/jats:italic>\n            . Closer inspection of the genome sequence data further revealed that reads covering SCC\n            <jats:italic>mec<\/jats:italic>\n            were \u223c10 times overrepresented compared to other parts of the chromosome. Quantitative PCR (qPCR) confirmed &gt;10-fold-higher levels of\n            <jats:italic>mecA<\/jats:italic>\n            DNA on the HoR34 chromosome, and MinION genome sequencing verified the presence of 10 tandem repeats of the SCC\n            <jats:italic>mec<\/jats:italic>\n            element. qPCR further demonstrated that subculture of HoR34 in various concentrations of oxacillin (0 to 100 \u03bcg\/ml) was accompanied by accordion-like contraction and amplification of the SCC\n            <jats:italic>mec<\/jats:italic>\n            element. Although slower growing than strain USA300, HoR34 outcompeted the parent strain in the presence of subinhibitory oxacillin. These data identify tandem amplification of the SCC\n            <jats:italic>mec<\/jats:italic>\n            element as a new mechanism of high-level methicillin resistance in MRSA, which may provide a competitive advantage for MRSA under antibiotic selection.\n          <\/jats:p>","DOI":"10.1128\/aac.00869-17","type":"journal-article","created":{"date-parts":[[2017,7,18]],"date-time":"2017-07-18T00:40:21Z","timestamp":1500338421000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":28,"title":["Tandem Amplification of the Staphylococcal Cassette Chromosome\n            <i>mec<\/i>\n            Element Can Drive High-Level Methicillin Resistance in Methicillin-Resistant Staphylococcus aureus"],"prefix":"10.1128","volume":"61","author":[{"given":"Laura A.","family":"Gallagher","sequence":"first","affiliation":[{"name":"Department of Microbiology, School of Natural Sciences, National University of Ireland, Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Coughlan","sequence":"additional","affiliation":[{"name":"School of Mathematics, Statistics and Applied Mathematics, National University of Ireland, Galway, Ireland"},{"name":"School of Biotechnology, Dublin City University, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikki S.","family":"Black","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School of Natural Sciences, National University of Ireland, Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierce","family":"Lalor","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School of Natural Sciences, National University of Ireland, Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine M.","family":"Waters","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School of Natural Sciences, National University of Ireland, Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"Wee","sequence":"additional","affiliation":[{"name":"Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, Scotland, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mick","family":"Watson","sequence":"additional","affiliation":[{"name":"Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, Scotland, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Downing","sequence":"additional","affiliation":[{"name":"School of Biotechnology, Dublin City University, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Ross","family":"Fitzgerald","sequence":"additional","affiliation":[{"name":"Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, Scotland, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard T. A.","family":"Fleming","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School of Natural Sciences, National University of Ireland, Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3866-7161","authenticated-orcid":false,"given":"James P.","family":"O'Gara","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School of Natural Sciences, National University of Ireland, Galway, 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