{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T07:46:37Z","timestamp":1790235997573,"version":"4.1.0"},"reference-count":44,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2005,5,1]],"date-time":"2005-05-01T00:00:00Z","timestamp":1114905600000},"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":[[2005,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>A novel OXA-type enzyme, named OXA-46, was found to be encoded by a gene cassette inserted into a class 1 integron from a multidrug-resistant<jats:italic>Pseudomonas aeruginosa<\/jats:italic>clinical isolate. The variable region of the integron also contained a<jats:italic>bla<\/jats:italic><jats:sub>VIM-1<\/jats:sub>metallo-\u03b2-lactamase cassette and a duplicated<jats:italic>aacA4<\/jats:italic>aminoglycoside acetyltransferase cassette. OXA-46 belongs to the OXA-2 lineage of class D \u03b2-lactamases. It exhibits 78% sequence identity with OXA-2 and the highest similarity (around 92% identity) with another OXA-type enzyme detected in clinical isolates of<jats:italic>Burkholderia cepacia<\/jats:italic>and in unidentified bacteria from a wastewater plant. Expression of<jats:italic>bla<\/jats:italic><jats:sub>OXA-46<\/jats:sub>in<jats:italic>Escherichia coli<\/jats:italic>decreased susceptibility to penicillins and narrow-spectrum cephalosporins but not to extended-spectrum cephalosporins, cefsulodin, aztreonam, or carbapenems. The enzyme was overproduced in<jats:italic>E. coli<\/jats:italic>and purified by two anion-exchange chromatography steps (approximate yield, 6 mg\/liter). OXA-46 was made of a 28.5-kDa polypeptide and exhibited an alkaline pI (7.8). In its native form OXA-46 appeared to be dimeric, and the oligomerization state was not affected by EDTA. Kinetic analysis of OXA-46 revealed a specificity for narrow-spectrum substrates, including oxacillin, other penicillins (but not temocillin), and narrow-spectrum cephalosporins. The enzyme apparently did not interact with temocillin, oxyimino-cephalosporins, or aztreonam. OXA-46 was inactivated by tazobactam and carbapenems and, although less efficiently, also by clavulanic acid. Enzyme activity was not affected either by EDTA or by divalent cations and exhibited low susceptibility to NaCl. These findings underscore the functional and structural diversity that can be encountered among class D \u03b2-lactamases.<\/jats:p>","DOI":"10.1128\/aac.49.5.1973-1980.2005","type":"journal-article","created":{"date-parts":[[2005,4,26]],"date-time":"2005-04-26T23:32:47Z","timestamp":1114558367000},"page":"1973-1980","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":33,"title":["OXA-46, a New Class D \u03b2-Lactamase of Narrow Substrate Specificity Encoded by a<i>bla<\/i><sub>VIM-1<\/sub>-Containing Integron from a<i>Pseudomonas aeruginosa<\/i>Clinical Isolate"],"prefix":"10.1128","volume":"49","author":[{"given":"Francesco","family":"Giuliani","sequence":"first","affiliation":[{"name":"Dipartimento di Biologia Molecolare, Laboratorio di Fisiologia e Biotecnologia dei Microrganismi, Universita\u0300 di Siena, I-53100 Siena"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Denis","family":"Docquier","sequence":"additional","affiliation":[{"name":"Dipartimento di Biologia Molecolare, Laboratorio di Fisiologia e Biotecnologia dei Microrganismi, Universita\u0300 di Siena, I-53100 Siena"},{"name":"Centre d'Inge\u0301nierie des Prote\u0301ines &amp; Laboratoire d'Enzymologie, Universite\u0301 de Lie\u0300ge, B-4000 Lie\u0300ge, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Letizia","family":"Riccio","sequence":"additional","affiliation":[{"name":"Dipartimento di Biologia Molecolare, Laboratorio di Fisiologia e Biotecnologia dei Microrganismi, Universita\u0300 di Siena, I-53100 Siena"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Pagani","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Morfologiche, Eidologiche e Cliniche, Sezione di Microbiologia, Universita\u0300 di Pavia, I-27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gian Maria","family":"Rossolini","sequence":"additional","affiliation":[{"name":"Dipartimento di Biologia Molecolare, Laboratorio di Fisiologia e Biotecnologia dei Microrganismi, Universita\u0300 di Siena, I-53100 Siena"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00239-002-2328-y"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2004.05.028"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.6.1211"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2672.2002.01612.x"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(85)80989-3"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.4.785"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(87)90609-5"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.6.1823-1830.2002"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1198-743X.2004.00858.x"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.12.3509-3516.2001"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.11.3003-3007.2000"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.6.2043-2048.2004"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.241442898"},{"key":"e_1_3_2_15_2","first-page":"192","volume":"207","year":"1997","unstructured":"Hall, R. 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