{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T05:02:18Z","timestamp":1780376538095,"version":"3.54.1"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2005,7,1]],"date-time":"2005-07-01T00:00:00Z","timestamp":1120176000000},"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":[[2005,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            We found ampicillin- and imipenem-resistant isolates of\n            <jats:italic>vanA<\/jats:italic>\n            -possessing\n            <jats:italic>Enterococcus faecalis<\/jats:italic>\n            with MICs of 8 to 16 \u03bcg\/ml and 4 to 32 \u03bcg\/ml, respectively. There have been few reports about penicillin- and imipenem-resistant\n            <jats:italic>E. faecalis<\/jats:italic>\n            . Two mechanisms of beta-lactam resistance in\n            <jats:italic>E. faecalis<\/jats:italic>\n            , the production of beta-lactamase and the overproduction of penicillin-binding proteins (PBPs), have been reported. The resistant isolates in the current study did not produce any beta-lactamases and analysis of the PBPs showed no overproduction. However, the affinities of PBP4 for beta-lactams in the resistant strains were lower than those of susceptible strains but the affinities of other PBPs for beta-lactams did not change. Accordingly, whole\n            <jats:italic>pbp4<\/jats:italic>\n            fragments from these resistant isolates were sequenced. Two amino acid substitutions at positions 520 and 605 were observed in the highly resistant strains compared to the susceptible ones, Pro520Ser and Tyr605His, and a single Tyr605His amino acid substitution was found in the low-resistance strains. These two point mutations exist in the region between the active-site-defining motifs SDN and KTG of the penicillin-binding domain, the main target of beta-lactams. A strong correlation was seen between these substitutions and decreasing affinities of PBP4 to beta-lactams. In\n            <jats:italic>E. faecalis<\/jats:italic>\n            , resistance due to mutations in PBPs has not been reported, though it has in\n            <jats:italic>Enterococcus faecium<\/jats:italic>\n            . Our results suggest that development of high-level resistance to penicillins and imipenem depends on point mutations of PBP4 at positions 520 and 605.\n          <\/jats:p>","DOI":"10.1128\/aac.49.7.2954-2958.2005","type":"journal-article","created":{"date-parts":[[2005,6,25]],"date-time":"2005-06-25T02:22:50Z","timestamp":1119666170000},"page":"2954-2958","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":85,"title":["Mechanisms of Resistance to Imipenem and Ampicillin in\n            <i>Enterococcus faecalis<\/i>"],"prefix":"10.1128","volume":"49","author":[{"given":"Seiji","family":"Ono","sequence":"first","affiliation":[{"name":"Department of Urology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanisi-Ku, Kitakyusyu 807-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuro","family":"Muratani","sequence":"additional","affiliation":[{"name":"Department of Urology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanisi-Ku, Kitakyusyu 807-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuro","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Urology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanisi-Ku, Kitakyusyu 807-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1093\/jac\/26.5.613","volume":"26","year":"1990","unstructured":"Al-Obeid, S., L. 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