{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T04:32:11Z","timestamp":1777609931534,"version":"3.51.4"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2008,7,1]],"date-time":"2008-07-01T00:00:00Z","timestamp":1214870400000},"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":[[2008,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            CTX-M \u03b2-lactamases, which show a high cefotaxime hydrolytic activity, constitute the most prevalent extended-spectrum \u03b2-lactamase (ESBL) type found among clinical isolates. The recent explosive diversification of CTX-M enzymes seems to have taken place due to the appearance of more efficient enzymes which are capable of hydrolyzing both cefotaxime and ceftazidime, especially among the CTX-M-1 cluster. A combined strategy of in vitro stepwise evolution experiments using\n            <jats:italic>bla<\/jats:italic>\n            <jats:sub>CTX-M-1<\/jats:sub>\n            ,\n            <jats:italic>bla<\/jats:italic>\n            <jats:sub>CTX-M-3<\/jats:sub>\n            , and\n            <jats:italic>bla<\/jats:italic>\n            <jats:sub>CTX-M-10<\/jats:sub>\n            genes and site-directed mutagenesis has been used to evaluate the role of ceftazidime and other \u03b2-lactam antibiotics in triggering the diversity found among enzymes belonging to this cluster. Two types of mutants, P167S and D240G, displaying high ceftazidime MICs but reduced resistance to cefotaxime and\/or cefepime, respectively, were identified. Such an antagonistic pleiotropic effect was particularly evident with P167S\/T mutations. The incompatibility between P167S and D240G changes was demonstrated, since double mutants reduced susceptibility to both ceftazidime and cefotaxime-cefepime; this may explain the absence of strains containing both mutations in the clinical environment. The role of A77V and N106S mutations, which are frequently associated with P167S\/T and\/or D240G, respectively, in natural strains, was investigated. The presence of A77V and N106S contributes to restore a high-level cefotaxime resistance phenotype, but only when associated with mutations P167S and D240G, respectively. However, A77V mutation increases resistance to both cefotaxime and ceftazidime when associated with CTX-M-10. This suggests that in this context this mutation might be considered a primary site involved in resistance to broad-spectrum cephalosporins.\n          <\/jats:p>","DOI":"10.1128\/aac.01658-07","type":"journal-article","created":{"date-parts":[[2008,4,29]],"date-time":"2008-04-29T00:53:45Z","timestamp":1209430425000},"page":"2377-2382","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":38,"title":["Mutational Events in Cefotaximase Extended-Spectrum \u03b2-Lactamases of the CTX-M-1 Cluster Involved in Ceftazidime Resistance"],"prefix":"10.1128","volume":"52","author":[{"given":"A\u0302ngela","family":"Novais","sequence":"first","affiliation":[{"name":"Hospital Universitario Ramo\u0301n y Cajal, IMSALUD, Madrid, Spain"}]},{"given":"Rafael","family":"Canto\u0301n","sequence":"additional","affiliation":[{"name":"Hospital Universitario Ramo\u0301n y Cajal, IMSALUD, Madrid, Spain"},{"name":"Unidad de Resistencia a Antibio\u0301ticos y Virulencia Bacteriana (RYC-CSIC), and CIBER-ESP, Madrid, Spain"}]},{"given":"Teresa M.","family":"Coque","sequence":"additional","affiliation":[{"name":"Hospital Universitario Ramo\u0301n y Cajal, IMSALUD, Madrid, Spain"},{"name":"Unidad de Resistencia a Antibio\u0301ticos y Virulencia Bacteriana (RYC-CSIC), and CIBER-ESP, Madrid, Spain"}]},{"given":"Andre\u0301s","family":"Moya","sequence":"additional","affiliation":[{"name":"Institut Cavanilles de Biodiversitat i Biologia Evolutiva, Universitat de Vale\u0300ncia, Valencia, Spain"}]},{"given":"Fernando","family":"Baquero","sequence":"additional","affiliation":[{"name":"Hospital Universitario Ramo\u0301n y Cajal, IMSALUD, Madrid, Spain"},{"name":"Unidad de Resistencia a Antibio\u0301ticos y Virulencia Bacteriana (RYC-CSIC), and CIBER-ESP, Madrid, Spain"}]},{"given":"Juan Carlos","family":"Gala\u0301n","sequence":"additional","affiliation":[{"name":"Hospital Universitario Ramo\u0301n y Cajal, IMSALUD, Madrid, Spain"},{"name":"Unidad de Resistencia a Antibio\u0301ticos y Virulencia Bacteriana (RYC-CSIC), and CIBER-ESP, Madrid, Spain"}]}],"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":"10.1093\/jac\/dkl252"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/160.3.823"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01647010"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2006.08.011"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.6.2308-2313.2004"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2005.02.010"},{"key":"e_1_3_2_9_2","first-page":"M2","year":"2006","unstructured":"Clinical and Laboratory Standards Institute. 2006. 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