{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T18:22:42Z","timestamp":1793298162707,"version":"4.5.0"},"reference-count":16,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2004,8,1]],"date-time":"2004-08-01T00:00:00Z","timestamp":1091318400000},"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":[[2004,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    We tested the impact of individual PBP 5 mutations on expression of ampicillin resistance in\n                    <jats:italic>Enterococcus faecium<\/jats:italic>\n                    using a shuttle plasmid designed to facilitate expression of cloned\n                    <jats:italic>pbp5<\/jats:italic>\n                    in ampicillin-susceptible\n                    <jats:italic>E. faecium<\/jats:italic>\n                    D344SRF. Substitutions that had been implicated in contributing to the resistance of clinical strains conferred only modest levels of resistance when they were present as single point mutations. The levels of resistance were amplified when some mutations were present in combination. In particular, a methionine-to-alanine change at position 485 (in close proximity to the active site) combined with the insertion of a serine at position 466 (located in a loop that forms the outer edge of the active site) was associated with the highest levels of resistance to all \u03b2-lactams. Affinity for penicillin generally correlated with \u03b2-lactam MICs for the mutants, but these associations were not strictly proportional.\n                  <\/jats:p>","DOI":"10.1128\/aac.48.8.3028-3032.2004","type":"journal-article","created":{"date-parts":[[2004,7,23]],"date-time":"2004-07-23T14:45:20Z","timestamp":1090593920000},"page":"3028-3032","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":122,"title":["Impact of Specific\n                    <i>pbp5<\/i>\n                    Mutations on Expression of \u03b2-Lactam Resistance in\n                    <i>Enterococcus faecium<\/i>"],"prefix":"10.1128","volume":"48","author":[{"given":"Louis B.","family":"Rice","sequence":"first","affiliation":[{"name":"Medical and Research Services, Louis Stokes Cleveland VA Medical Center"},{"name":"Case Western Reserve University, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Bellais","sequence":"additional","affiliation":[{"name":"LRMA, INSERM E0004, Universite\u0301 Paris VI, 75270 Paris Cedex 06, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lenore L.","family":"Carias","sequence":"additional","affiliation":[{"name":"Case Western Reserve University, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Hutton-Thomas","sequence":"additional","affiliation":[{"name":"Medical and Research Services, Louis Stokes Cleveland VA Medical Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Bonomo","sequence":"additional","affiliation":[{"name":"Medical and Research Services, Louis Stokes Cleveland VA Medical Center"},{"name":"Case Western Reserve University, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Caspers","sequence":"additional","affiliation":[{"name":"Basilea Pharmaceutica, CH-4005 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malcolm G. P.","family":"Page","sequence":"additional","affiliation":[{"name":"Basilea Pharmaceutica, CH-4005 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Gutmann","sequence":"additional","affiliation":[{"name":"LRMA, INSERM E0004, Universite\u0301 Paris VI, 75270 Paris Cedex 06, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.180.17.4426-4434.1998"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1042\/bj3380153","volume":"338","year":"1999","unstructured":"Chittock, R. S., S. Ward, A. S. Wilkinson, P. Caspers, B. Mensch, M. G. Page, and C. W. Wharton. 1999. Hydrogen bonding and protein perturbation in beta-lactam acyl-enzymes of Streptococcus pneumoniae penicillin-binding protein PBP2x. Biochem. J.338(Pt 1):153-159.","journal-title":"Biochem. 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Science234:849-855.","journal-title":"Science"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsb0396-284"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1097(97)00423-0"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.5.1480-1486.2001"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1086\/515605"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-002-8500-0"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.9.2594-2597.2001"},{"key":"e_1_3_2_16_2","first-page":"1933","volume":"131","year":"1985","unstructured":"Williamson, R., C. LaBouguenec, L. Gutmann, and T. Horaud. 1985. One or two low affinity penicillin-binding proteins may be responsible for the range of susceptibility of Enterococcus faecium to penicillin. J. Gen. Microbiol.131:1933-1940.","journal-title":"J. Gen. 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