{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:32:11Z","timestamp":1790685131922,"version":"4.1.0"},"reference-count":33,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2012,5,1]],"date-time":"2012-05-01T00:00:00Z","timestamp":1335830400000},"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":[[2012,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    With voriconazole (VRC) being approved as the first choice in treating invasive aspergillosis (IA) and its increasing use in treatment, a VRC-resistant strain of\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Aspergillus flavus<\/jats:named-content>\n                    , the second leading cause of IA after\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Aspergillus fumigatus<\/jats:named-content>\n                    , has emerged. The VRC-resistant strain of\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">A. flavus<\/jats:named-content>\n                    was isolated for the first time from the surgical lung specimen of an IA patient with no response to VRC therapy. In order to ascertain the mechanism of VRC resistance, the azole target enzyme genes in this strain of\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">A. flavus<\/jats:named-content>\n                    were cloned and sequenced, and 4 mutations generating amino acid residue substitutions were found in the\n                    <jats:italic>cyp51C<\/jats:italic>\n                    gene. To further determine the role of this mutated gene for VRC resistance in\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">A. flavus<\/jats:named-content>\n                    , an\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Agrobacterium tumefaciens<\/jats:named-content>\n                    -mediated gene replacement approach was applied. Consequently, the mutated\n                    <jats:italic>cyp51C<\/jats:italic>\n                    gene from this\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">A. flavus<\/jats:named-content>\n                    strain was proven to confer the VRC resistance. Finally, to discern the one out of the four mutations in the\n                    <jats:italic>cyp51C<\/jats:italic>\n                    gene that is responsible for contributing to VRC resistance, a site-directed gene mutagenesis procedure combined with a gene replacement method was performed. As a result, the T788G missense mutation in the\n                    <jats:italic>cyp51C<\/jats:italic>\n                    gene was identified as responsible for VRC resistance in\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">A. flavus<\/jats:named-content>\n                    . These findings indicated that the detection of this mutation in\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">A. flavus<\/jats:named-content>\n                    could serve as an indicator for physicians to avoid the use of VRC during IA treatment. Further comprehensive surveillance for antifungal susceptibility, as well as intensive study on the mechanism of azole resistance in\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">A. flavus<\/jats:named-content>\n                    causing IA, would be required to fully understand this mechanism.\n                  <\/jats:p>","DOI":"10.1128\/aac.05477-11","type":"journal-article","created":{"date-parts":[[2012,2,7]],"date-time":"2012-02-07T00:51:54Z","timestamp":1328575914000},"page":"2598-2603","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":64,"title":["The T788G Mutation in the\n                    <i>cyp51C<\/i>\n                    Gene Confers Voriconazole Resistance in Aspergillus flavus Causing Aspergillosis"],"prefix":"10.1128","volume":"56","author":[{"given":"Wei","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Dermatology, Peking University First Hospital, Research Center for Medical Mycology, Peking University, Beijing, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Peking University First Hospital, Research Center for Medical Mycology, Peking University, Beijing, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Peking University First Hospital, Research Center for Medical Mycology, Peking University, Beijing, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weixia","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Peking University First Hospital, Research Center for Medical Mycology, Peking University, Beijing, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Peking University First Hospital, Research Center for Medical Mycology, Peking University, Beijing, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingfang","family":"Bu","sequence":"additional","affiliation":[{"name":"Centre Labs, Peking University First Hospital, Beijing, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoyu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Peking University First Hospital, Research Center for Medical Mycology, Peking University, Beijing, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-51-4-344"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2006.01.001"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.37.5.1532-1535.1999"},{"key":"e_1_3_2_5_2","volume-title":"CLSI document M38-A2","author":"Clinical and Laboratory Standards Institute","year":"2008","unstructured":"Clinical and Laboratory Standards Institute. 2008. 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