{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T19:12:12Z","timestamp":1775070732415,"version":"3.50.1"},"reference-count":46,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2013,7,1]],"date-time":"2013-07-01T00:00:00Z","timestamp":1372636800000},"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":[[2013,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            In response to \u03b2-lactam chemotherapy,\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            has acquired two resistance determinants:\n            <jats:italic>blaZ<\/jats:italic>\n            , coding for \u03b2-lactamase, which confers resistance to penicillins only, and\n            <jats:italic>mecA<\/jats:italic>\n            , coding for an extra cell wall cross-linking enzyme with reduced affinity for virtually all other \u03b2-lactams. The transcriptional control of both resistance determinants is regulated by homologous repressors (BlaI and MecI, respectively) and sensor inducers (BlaR1 and MecR1, respectively). There is a cross-talk between the two regulatory systems, and it has been demonstrated that\n            <jats:italic>bla<\/jats:italic>\n            regulators stabilize the\n            <jats:italic>mecA<\/jats:italic>\n            acquisition. In a recent study, we have unexpectedly observed that in most MRSA strains, there was no significant change in the resistance phenotype upon the overexpression in\n            <jats:italic>trans<\/jats:italic>\n            of a MecI repressor, whereas in those few strains negative for the\n            <jats:italic>bla<\/jats:italic>\n            locus, there was a massive decrease of resistance (D. C. Oliveira and H. de Lencastre, PLoS One 6:e23287, 2011). Here, we demonstrate that, contrary to what is currently accepted, the\n            <jats:italic>bla<\/jats:italic>\n            regulatory system efficiently disrupts the strong MecI-mediated repression on\n            <jats:italic>mecA<\/jats:italic>\n            , enabling the optimal expression of resistance. This effect appears to be due to the formation of MecI::BlaI heterodimers that might bind less efficiently to the\n            <jats:italic>mecA<\/jats:italic>\n            promoter and become nonfunctional due to the proteolytic inactivation of the BlaI monomer. In addition, we have also observed that the presence of\n            <jats:italic>bla<\/jats:italic>\n            regulators may enhance dramatically the expression of \u03b2-lactam resistance in MRSA strains with constitutive\n            <jats:italic>mecA<\/jats:italic>\n            expression, compensating for the fitness cost imposed by the large \u03b2-lactamase plasmid. These observations point to important unrecognized roles of the\n            <jats:italic>bla<\/jats:italic>\n            locus for the expression of the 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) phenotype.\n          <\/jats:p>","DOI":"10.1128\/aac.02621-12","type":"journal-article","created":{"date-parts":[[2013,4,16]],"date-time":"2013-04-16T01:48:44Z","timestamp":1366076924000},"page":"3037-3045","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":40,"title":["Redefining the Role of the \u03b2-Lactamase Locus in Methicillin-Resistant Staphylococcus aureus: \u03b2-Lactamase Regulators Disrupt the MecI-Mediated Strong Repression on\n            <i>mecA<\/i>\n            and Optimize the Phenotypic Expression of Resistance in Strains with Constitutive\n            <i>mecA<\/i>\n            Expression"],"prefix":"10.1128","volume":"57","author":[{"given":"Pedro","family":"Ar\u00eade","sequence":"first","affiliation":[{"name":"CREM, Department of Life Sciences, Faculdade de Ci\u00eancias e Tecnologia, Universidade Nova de Lisboa, Caparica, Portugal"}]},{"given":"Joana","family":"Ministro","sequence":"additional","affiliation":[{"name":"CREM, Department of Life Sciences, Faculdade de Ci\u00eancias e Tecnologia, Universidade Nova de Lisboa, Caparica, Portugal"}]},{"given":"Duarte C.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"CREM, Department of Life Sciences, Faculdade de Ci\u00eancias e Tecnologia, Universidade Nova de Lisboa, Caparica, Portugal"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199808203390806"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)61999-1"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(10)70053-0"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(87)80373-3"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj0830229"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj0880452"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.8.4.557"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.6.1449"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00579-09"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(92)80039-J"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.36.1.25"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.37.5.1144"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/45.2.139"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.180.8.2160-2166.1998"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.183.23.6862-6868.2001"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1997.4051770.x"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.116.2.803-811.1973"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.185.18.5465-5472.2003"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002816"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023287"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.35.4.632"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.2144\/97234bm22"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.180.23.6077-6081.1998"},{"key":"e_1_3_2_25_2","volume-title":"Short protocols in molecular biology","author":"Ausubel FM","year":"1992","unstructured":"AusubelFM BrentR KingstonRE MooreDD SeidmanJG SmithJA StruhlK. 1992. 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