{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T06:18:21Z","timestamp":1775283501457,"version":"3.50.1"},"reference-count":31,"publisher":"American Society for Microbiology","issue":"17","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"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":["J Bacteriol"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Resistance to methicillin and other \u03b2-lactam antibiotics in staphylococci is due to\n            <jats:italic>mecA<\/jats:italic>\n            , which is carried on a genomic island, staphylococcal cassette chromosome\n            <jats:italic>mec<\/jats:italic>\n            (SCC\n            <jats:italic>mec<\/jats:italic>\n            ). The chromosomal excision and integration of SCC\n            <jats:italic>mec<\/jats:italic>\n            are mediated by the site-specific recombinase CcrAB or CcrC, encoded within this element. A plasmid-borne system was constructed to assess the activities of CcrA and CcrB in the excision and integration of SCC\n            <jats:italic>mec<\/jats:italic>\n            in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Escherichia coli<\/jats:named-content>\n            and\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            . The excision frequency in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. coli<\/jats:named-content>\n            mediated by CcrAB from 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) strain N315 was only 9.2%, while the integration frequency was 31.4%. In\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            the excision and integration frequencies were 11.0% and 18.7%, respectively. Truncated mutants identified the N-terminal domain of either CcrB or CcrA to be necessary for both integration and excision, while the C-terminal domain was important for recombination efficiency. Site-directed mutagenesis of the N-terminal domain identified S11 and R79 of CcrA and S16, R89, T149, and R151 of CcrB to be residues essential for catalytic activities, and the critical location of these residues was consistent with a model of the tertiary structure of the N terminus of CcrA and CcrB. Furthermore, CcrAB and CcrC, cloned from a panel of 6 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            strains and 2 methicillin-resistant\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Staphylococcus epidermidis<\/jats:named-content>\n            strains carrying SCC\n            <jats:italic>mec<\/jats:italic>\n            types II, IV, and V, also catalyzed integration at rates 1.3 to 10 times higher than the rates at which they catalyzed excision, similar to the results from N315. The tendency of SCC\n            <jats:italic>mec<\/jats:italic>\n            integration to be favored over excision may explain the low spontaneous excision frequency seen among MRSA strains.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Spontaneous excision of the genomic island (SCCmec) that encodes resistance to beta-lactam antibiotics (methicillin resistance) in staphylococci would convert a methicillin-resistant strain to a methicillin-susceptible strain, improving therapy of difficult-to-treat infections. This study characterizes a model system by which the relative frequencies of excision and integration can be compared. Using a plasmid-based model for excision and integration mediated by the recombinases CcrA and CcrB, integration occurred at a higher frequency than excision, consistent with the low baseline excision frequency seen in most strains. This model system can now be used to study conditions and drugs that may raise the SCC\n            <jats:italic>mec<\/jats:italic>\n            excision frequency and generate strains that are beta-lactam susceptible.\n          <\/jats:p>","DOI":"10.1128\/jb.00078-15","type":"journal-article","created":{"date-parts":[[2015,6,10]],"date-time":"2015-06-10T19:09:54Z","timestamp":1433963394000},"page":"2754-2761","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["A Plasmid-Borne System To Assess the Excision and Integration of Staphylococcal Cassette Chromosome\n            <i>mec<\/i>\n            Mediated by CcrA and CcrB"],"prefix":"10.1128","volume":"197","author":[{"given":"Lei","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Infectious Diseases, School of Medicine, Virginia Commonwealth University, Richmond, Virginia, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mostafa H.","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Institute for Structural Biology and Drug Discovery, Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin K.","family":"Safo","sequence":"additional","affiliation":[{"name":"Institute for Structural Biology and Drug Discovery, Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gordon L.","family":"Archer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Infectious Diseases, School of Medicine, Virginia Commonwealth University, Richmond, Virginia, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"crossref","DOI":"10.1002\/9781444308464","volume-title":"Staphylococci in human disease","author":"Crossley K","year":"2009","unstructured":"Crossley K, Jefferson K, Archer GL, Fowler VG, Jr (ed). 2009. 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