{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:36:27Z","timestamp":1790750187841,"version":"4.1.0"},"reference-count":33,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2016,4,1]],"date-time":"2016-04-01T00:00:00Z","timestamp":1459468800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000098","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["2 R01 AI457838-15"],"award-info":[{"award-number":["2 R01 AI457838-15"]}],"id":[{"id":"10.13039\/100000098","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":[[2016,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Resistance to beta-lactam antibiotics 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) requires the presence of an acquired genetic determinant,\n                    <jats:italic>mecA<\/jats:italic>\n                    or\n                    <jats:italic>mecC<\/jats:italic>\n                    , which encode penicillin-binding protein PBP2A or PBP2A\u2032, respectively. Although all MRSA strains share a mechanism of resistance, the phenotypic expression of beta-lactam resistance shows considerable strain-to-strain variation. The stringent stress response, a stress response that results from nutrient limitation, was shown to play a key role in determining the resistance level of an MRSA strain. In the present study, we validated the impact of the stringent stress response on transcription and translation of\n                    <jats:italic>mecA<\/jats:italic>\n                    in the MRSA clinical isolate strain N315, which also carries known regulatory genes (\n                    <jats:italic>mecI\/mecR1<\/jats:italic>\n                    \/\n                    <jats:italic>mecR2<\/jats:italic>\n                    and\n                    <jats:italic>blaI\/blaR1<\/jats:italic>\n                    ) for\n                    <jats:italic>mecA<\/jats:italic>\n                    transcription. We showed that the impact of the stringent stress response on the resistance level may be restricted to beta-lactam resistance based on a \u201cforeign\u201d determinant such as\n                    <jats:italic>mecA<\/jats:italic>\n                    , as opposed to resistance based on mutations in the native\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                    determinant\n                    <jats:italic>pbpB<\/jats:italic>\n                    (encoding PBP2). Our observations demonstrate that high-level resistance mediated by the stringent stress response follows the current model of beta-lactam resistance in which the native PBP2 protein is also essential for expression of the resistance phenotype. We also show that the\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Staphylococcus sciuri pbpD<\/jats:named-content>\n                    gene (also called\n                    <jats:italic>mecAI<\/jats:italic>\n                    ), the putative evolutionary precursor of\n                    <jats:italic>mecA<\/jats:italic>\n                    , confers oxacillin resistance in an\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                    strain, generating a heterogeneous phenotype that can be converted to high and homogenous resistance by induction of the stringent stress response in the bacteria.\n                  <\/jats:p>","DOI":"10.1128\/aac.02697-15","type":"journal-article","created":{"date-parts":[[2016,2,1]],"date-time":"2016-02-01T23:44:41Z","timestamp":1454370281000},"page":"2311-2317","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":65,"title":["Role of the Stringent Stress Response in the Antibiotic Resistance Phenotype of Methicillin-Resistant Staphylococcus aureus"],"prefix":"10.1128","volume":"60","author":[{"given":"Sandra","family":"Aedo","sequence":"first","affiliation":[{"name":"Laboratory of Microbiology &amp; Infectious Diseases, The Rockefeller University, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Tomasz","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology &amp; Infectious Diseases, The Rockefeller University, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.6.1449"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(11)70126-8"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.158.2.513-516.1984"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)49904-3"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.38.4.724"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.35.1.124"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02389872"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/33.1.7"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01000-13"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1089\/mdr.2013.0053"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0082814"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0073512"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0099605"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkp164"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.62.081307.162903"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2008.02.001"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05363-11"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.183.23.6862-6868.2001"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-060614-034516"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.187.5.1815-1824.2005"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.183.22.6525-6531.2001"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.9.e45"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.395962"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.12.2680"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.191260798"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00049-08"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.183.8.2417-2424.2001"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.29078-0"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi7004587"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1089\/mdr.1996.2.377"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.185.2.645-653.2003"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0402521101"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01549-07"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.02697-15","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.02697-15","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T15:33:01Z","timestamp":1645457581000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.02697-15"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,4]]},"references-count":33,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2016,4]]}},"alternative-id":["10.1128\/AAC.02697-15"],"URL":"https:\/\/doi.org\/10.1128\/aac.02697-15","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,4]]},"assertion":[{"value":"2015-11-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-01-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-03-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}