{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T11:29:45Z","timestamp":1791545385998,"version":"4.3.4"},"reference-count":32,"publisher":"American Society for Microbiology","issue":"24","license":[{"start":{"date-parts":[[2003,12,15]],"date-time":"2003-12-15T00:00:00Z","timestamp":1071446400000},"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":[[2003,12,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:italic>Enterococcus\nfaecalis<\/jats:italic>\n            produces a specific penicillin-binding protein (PBP5)\nthat mediates high-level resistance to the cephalosporin class of\u03b2\n-lactam antibiotics. Deletion of a locus encoding a previously\nuncharacterized two-component regulatory system of\n            <jats:italic>E. faecalis<\/jats:italic>\n            (\n            <jats:italic>croRS<\/jats:italic>\n            ) led to a 4,000-fold reduction in the MIC of the\nexpanded-spectrum cephalosporin ceftriaxone. The cytoplasmic domain of\nthe sensor kinase (CroS) was purified and shown to catalyze\nATP-dependent autophosphorylation followed by transfer of the phosphate\nto the mated response regulator (CroR). The\n            <jats:italic>croR<\/jats:italic>\n            and\n            <jats:italic>croS<\/jats:italic>\n            genes were cotranscribed from a promoter (\n            <jats:italic>croRp<\/jats:italic>\n            )\nlocated in the\n            <jats:italic>rrnC-croR<\/jats:italic>\n            intergenic region. A putative\nseryl-tRNA synthetase gene (\n            <jats:italic>serS<\/jats:italic>\n            ) located immediately\ndownstream from\n            <jats:italic>croS<\/jats:italic>\n            did not appear to be a target of CroRS\nregulation or to play a role in ceftriaxone resistance. A plasmid-borne\n            <jats:italic>croRp-lacZ<\/jats:italic>\n            fusion was\n            <jats:italic>trans<\/jats:italic>\n            -activated by the CroRS\nsystem in response to the presence of ceftriaxone in the culture\nmedium. The fusion was also induced by representatives of other classes\nof \u03b2-lactam antibiotics and by inhibitors of early and late\nsteps of peptidoglycan synthesis. The\n            <jats:italic>croRS<\/jats:italic>\n            null mutant\nproduced PBP5, and expression of an additional copy of\n            <jats:italic>pbp5<\/jats:italic>\n            under the control of a heterologous promoter did not restore\nceftriaxone resistance. Deletion of\n            <jats:italic>croRS<\/jats:italic>\n            was not associated\nwith any defect in the synthesis of the nucleotide precursor\nUDP-MurNAc-pentapeptide or of the\n            <jats:sc>d<\/jats:sc>\n            -Ala\n            <jats:sub>4<\/jats:sub>\n            \u2192\n            <jats:sc>l<\/jats:sc>\n            -Ala-\n            <jats:sc>l<\/jats:sc>\n            -Ala-Lys\n            <jats:sub>3<\/jats:sub>\n            peptidoglycan cross-bridge. Thus, the\n            <jats:italic>croRS<\/jats:italic>\n            mutant was\nsusceptible to ceftriaxone despite the production of PBP5 and the\nsynthesis of wild-type peptidoglycan precursors. These observations\nconstitute the first description of regulatory genes essential for\nPBP5-mediated \u03b2-lactam resistance in\nenterococci.\n          <\/jats:p>","DOI":"10.1128\/jb.185.24.7184-7192.2003","type":"journal-article","created":{"date-parts":[[2003,12,2]],"date-time":"2003-12-02T01:43:08Z","timestamp":1070329388000},"page":"7184-7192","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":100,"title":["The CroRS Two-Component Regulatory System Is Requiredfor Intrinsic \u03b2-Lactam Resistance in\n            <i>Enterococcusfaecalis<\/i>"],"prefix":"10.1128","volume":"185","author":[{"given":"Yannick","family":"Comenge","sequence":"first","affiliation":[{"name":"INSERM\rE0004-LRMA, UFR Broussais-Ho\u0302tel Dieu, Universite\u0301 Paris VI,\r75270 Paris"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Richard","family":"Quintiliani","sequence":"additional","affiliation":[{"name":"University\rof Massachusetts Dartmouth, North Dartmouth, Massachusetts\r02747"},{"name":"Department of Emergency Medicine,\rSomerville Hospital, Harvard Medical School, Somerville,\rMassachusetts 02143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Li","sequence":"additional","affiliation":[{"name":"University\rof Massachusetts Dartmouth, North Dartmouth, Massachusetts\r02747"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lionnel","family":"Dubost","sequence":"additional","affiliation":[{"name":"De\u0301partement\rRe\u0301gulations, De\u0301veloppement et Diversite\u0301\rMole\u0301culaire, Museum National d'Histoire Naturel,\rUSM0502-CNRS UMR8041, 75005 Paris,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Paul","family":"Brouard","sequence":"additional","affiliation":[{"name":"De\u0301partement\rRe\u0301gulations, De\u0301veloppement et Diversite\u0301\rMole\u0301culaire, Museum National d'Histoire Naturel,\rUSM0502-CNRS UMR8041, 75005 Paris,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Emmanuel","family":"Hugonnet","sequence":"additional","affiliation":[{"name":"INSERM\rE0004-LRMA, UFR Broussais-Ho\u0302tel Dieu, Universite\u0301 Paris VI,\r75270 Paris"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Arthur","sequence":"additional","affiliation":[{"name":"INSERM\rE0004-LRMA, UFR Broussais-Ho\u0302tel Dieu, Universite\u0301 Paris VI,\r75270 Paris"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.174.8.2582-2591.1992"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.2.375-381.2001"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/BF00261186","volume":"219","year":"1989","unstructured":"Berger-Bachi, B., L. 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