{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T23:59:35Z","timestamp":1781567975079,"version":"3.54.5"},"reference-count":19,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2006,11,1]],"date-time":"2006-11-01T00:00:00Z","timestamp":1162339200000},"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":[[2006,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The molecular mechanisms of reduced susceptibility to cefixime in clinical isolates of\n            <jats:italic>Neisseria gonorrhoeae<\/jats:italic>\n            , particularly amino acid substitutions in mosaic penicillin-binding protein 2 (PBP2), were examined. The complete sequence of\n            <jats:italic>ponA<\/jats:italic>\n            ,\n            <jats:italic>penA<\/jats:italic>\n            , and\n            <jats:italic>por<\/jats:italic>\n            genes, encoding, respectively, PBP1, PBP2, and porin, were determined for 58 strains isolated in 2002 from Japan. Replacement of leucine 421 by proline in PBP1 and the mosaic-like structure of PBP2 were detected in 48 strains (82.8%) and 28 strains (48.3%), respectively. The presence of mosaic PBP2 was the main cause of the elevated cefixime MIC (4- to 64-fold). In order to identify the mutations responsible for the reduced susceptibility to cefixime in isolates with mosaic PBP2,\n            <jats:italic>penA<\/jats:italic>\n            genes with various mutations were transferred to a susceptible strain by genetic transformation. The susceptibility of partial recombinants and site-directed mutants revealed that the replacement of glycine 545 by serine (G545S) was the primary mutation, which led to a two- to fourfold increase in resistance to cephems. Replacement of isoleucine 312 by methionine (I312M) and valine 316 by threonine (V316T), in the presence of the G545S mutation, reduced susceptibility to cefixime, ceftibuten, and cefpodoxime by an additional fourfold. Therefore, three mutations (G545S, I312M, and V316T) in mosaic PBP2 were identified as the amino acid substitutions responsible for reduced susceptibility to cefixime in\n            <jats:italic>N. gonorrhoeae<\/jats:italic>\n            .\n          <\/jats:p>","DOI":"10.1128\/aac.00626-06","type":"journal-article","created":{"date-parts":[[2006,10,25]],"date-time":"2006-10-25T20:58:50Z","timestamp":1161809930000},"page":"3638-3645","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":104,"title":["Amino Acid Substitutions in Mosaic Penicillin-Binding Protein 2 Associated with Reduced Susceptibility to Cefixime in Clinical Isolates of\n            <i>Neisseria gonorrhoeae<\/i>"],"prefix":"10.1128","volume":"50","author":[{"given":"Sho","family":"Takahata","sequence":"first","affiliation":[{"name":"Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama 222-8567, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nami","family":"Senju","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama 222-8567, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumi","family":"Osaki","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama 222-8567, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuji","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama 222-8567, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Ida","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama 222-8567, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s101560170034"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.12.3744-3749.2002"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.176.2.333-337.1994"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1990.tb00664.x"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10156-002-0204-8"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.181.18.5591-5599.1999"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.1.137-143.2005"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.8.3185-3187.2004"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.12.3603-3606.2001"},{"key":"e_1_3_1_11_2","unstructured":"National Committee for Clinical Laboratory Standards. 2003. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved standard M7-A6. National Committee for Clinical Laboratory Standards Wayne Pa."},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.9.2811-2820.2002"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.188.7.2300-2308.2006"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.3.769-777.2002"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10156-005-0403-1"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00182388"},{"key":"e_1_3_1_17_2","doi-asserted-by":"crossref","first-page":"S15","DOI":"10.1016\/j.ijantimicag.2004.02.005","volume":"24","year":"2004","unstructured":"Tanaka, M., H. Nakayama, T. Notomi, S. Irie, Y. Tsunoda, A. Okadome, T. Saika, and I. Kobayashi. 2004. Antimicrobial resistance of Neisseria gonorrhoeae in Japan, 1993-2002: continuous increasing of ciprofloxacin-resistant isolates. Int. J. Antimicrob. Agents24S:S15-S22.","journal-title":"Int. J. Antimicrob. 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