{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T19:12:58Z","timestamp":1791141178814,"version":"4.1.0"},"reference-count":33,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[1998,5,1]],"date-time":"1998-05-01T00:00:00Z","timestamp":893980800000},"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":[[1998,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:italic>Escherichia coli<\/jats:italic>\n            TUM1083, which is resistant to ampicillin, carbenicillin, cephaloridine, cephalothin, piperacillin, cefuzonam, and aztreonam while being sensitive to cefoxitin, moxalactam, cefmetazole, ceftazidime, and imipenem, was isolated from the urine of a patient treated with \u03b2-lactam antibiotics. The \u03b2-lactamase (Toho-2) purified from the bacteria hydrolyzed \u03b2-lactam antibiotics such as penicillin G, carbenicillin, cephaloridine, cefoxitin, cefotaxime, ceftazidime, and aztreonam and especially had increased relative hydrolysis rates for cephalothin, cephaloridine, cefotaxime, and ceftizoxime. Different from other extended-spectrum \u03b2-lactamases, Toho-2 was inhibited 16-fold better by the \u03b2-lactamase inhibitor tazobactam than by clavulanic acid. Resistance to \u03b2-lactams was transferred by conjugation from\n            <jats:italic>E. coli<\/jats:italic>\n            TUM1083 to\n            <jats:italic>E. coli<\/jats:italic>\n            ML4909, and the transferred plasmid was about 54.4 kbp, belonging to the incompatibility group IncFII. The cefotaxime resistance gene for Toho-2 was subcloned from the 54.4-kbp plasmid. The sequence of the gene was determined, and the open reading frame of the gene was found to consist of 981 bases. The nucleotide sequence of the gene (DDBJ accession no.\n            <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"gen\" xlink:href=\"D89862\" xlink:type=\"simple\">D89862<\/jats:ext-link>\n            ) designated as\n            <jats:italic>bla<\/jats:italic>\n            <jats:sub>toho<\/jats:sub>\n            was found to have 76.3% identity to class A \u03b2-lactamase CTX-M-2 and 76.2% identity to Toho-1. It has 55.9% identity to SHV-1 \u03b2-lactamase and 47.5% identity to TEM-1 \u03b2-lactamase. Therefore, the newly isolated \u03b2-lactamase designated as Toho-2 produced by\n            <jats:italic>E. coli<\/jats:italic>\n            TUM1083 is categorized as an enzyme similar to Toho-1 group \u03b2-lactamases rather than to mutants of TEM or SHV enzymes. According to the amino acid sequence deduced from the DNA sequence, the precursor consisted of 327 amino acid residues. Comparison of Toho-2 with other \u03b2-lactamase (non-Toho-1 group) suggests that the substitutions of threonine for Arg-244 and arginine for Asn-276 are important for the extension of the substrate specificity.\n          <\/jats:p>","DOI":"10.1128\/aac.42.5.1181","type":"journal-article","created":{"date-parts":[[2018,10,9]],"date-time":"2018-10-09T00:31:56Z","timestamp":1539045116000},"page":"1181-1186","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":86,"title":["Cloning and Sequencing of the Gene Encoding Toho-2, a Class A \u03b2-Lactamase Preferentially Inhibited by Tazobactam"],"prefix":"10.1128","volume":"42","author":[{"given":"Ling","family":"Ma","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Department of Microbiology, Toho University School of Medicine, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143-8540,1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshikazu","family":"Ishii","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Microbiology, Toho University School of Medicine, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143-8540,1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaji","family":"Ishiguro","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Suntory Institute for Bioorganic Research, 1-1 Wakayamadai, Shimamoto, Osaka 618-8503,2 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Matsuzawa","sequence":"additional","affiliation":[{"name":"<!--label omitted: 3-->Department of Biotechnology, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657,3 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keizo","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Microbiology, Toho University School of Medicine, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143-8540,1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2760269"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.33.1.63"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4838(92)90121-S"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1042\/bj2510073","article-title":"Complete amino acid sequence of p453-plasmid-mediated PIT-2 \u03b2-lactamase (SHV-1).","volume":"251","author":"Barthelemy M.","year":"1988","unstructured":"Barthelemy M. 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