{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T21:07:46Z","timestamp":1791148066064,"version":"4.1.0"},"reference-count":39,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2002,5,1]],"date-time":"2002-05-01T00:00:00Z","timestamp":1020211200000},"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":[[2002,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Amino acid alterations in or flanking conserved motifs making up the active binding sites of penicillin-binding proteins (PBPs) 1a, 2b, and 2x of pneumococci were correlated with changes in affinities of penicillin, ampicillin, amoxicillin, cefditoren, cefuroxime, cefprozil, and cefaclor for these PBPs. Four penicillin-susceptible (PSSP), eight penicillin-intermediate (PISP), and six penicillin-resistant (PRSP) pneumococci were studied by DNA sequencing of the penicillin-binding sites of the\n            <jats:italic>pbp1a<\/jats:italic>\n            , -\n            <jats:italic>2x<\/jats:italic>\n            , and -\n            <jats:italic>2b<\/jats:italic>\n            genes of strains and by determining 50% inhibitory concentrations of the seven agents for PBP1a, -2x, and -2b. Two PSSP strains had alterations in PBP2x (L\n            <jats:sub>546<\/jats:sub>\n            \u2192V) (one strain) or PBP2b (T\n            <jats:sub>445<\/jats:sub>\n            \u2192A) (one strain). All eight PISP strains had at least two alterations--T\n            <jats:sub>338<\/jats:sub>\n            \u2192P or A or H\n            <jats:sub>394<\/jats:sub>\n            \u2192Y in PBP2X and T\n            <jats:sub>445<\/jats:sub>\n            \u2192A in BPB2b. All PRSP strains had the same changes seen in PISP strains, as well as T\n            <jats:sub>371<\/jats:sub>\n            \u2192A or S substitutions in PBP1a. The two most resistant PRSP strains had a second change in PBP2x (M\n            <jats:sub>339<\/jats:sub>\n            \u2192F) in a conserved motif. The affinities of penicillin and ampicillin for all three PBPs were decreased for PRSP and most PISP strains. The affinity of amoxicillin for PBP1a and -2x was decreased only for PRSP. Cefaclor and cefprozil showed decreased affinity of PRSP but not PISP for all three PBPs. Cefuroxime showed decreased affinity of PISP and PRSP for PBP1a and -2x but no change for PBP2b. Cefditoren showed no difference in PBP affinity based on penicillin or cefditoren MICs, indicating a different PBP target for this agent. Overall, the MICs for and PBP affinities of the strains correlated with the changes found in the PBP active binding sites.\n          <\/jats:p>","DOI":"10.1128\/aac.46.5.1273-1280.2002","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T10:09:01Z","timestamp":1027764541000},"page":"1273-1280","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":136,"title":["Effects of Amino Acid Alterations in Penicillin-Binding Proteins (PBPs) 1a, 2b, and 2x on PBP Affinities of Penicillin, Ampicillin, Amoxicillin, Cefditoren, Cefuroxime, Cefprozil, and Cefaclor in 18 Clinical Isolates of Penicillin-Susceptible, -Intermediate, and -Resistant Pneumococci"],"prefix":"10.1128","volume":"46","author":[{"given":"Kensuke","family":"Nagai","sequence":"first","affiliation":[{"name":"Department of Pathology, Hershey Medical Center, Hershey, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd A.","family":"Davies","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hershey Medical Center, Hershey, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Department of Pathology, Case Western Reserve University, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter C.","family":"Appelbaum","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hershey Medical Center, Hershey, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.9.2375"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/15.1.77"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"S29","DOI":"10.1086\/314057","volume":"31","year":"2000","unstructured":"Appelbaum, P. 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