{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:57:56Z","timestamp":1791262676094,"version":"4.1.0"},"reference-count":44,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2011,11,1]],"date-time":"2011-11-01T00:00:00Z","timestamp":1320105600000},"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":[[2011,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Multiple<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Aspergillus fumigatus<\/jats:named-content>isolates from a patient with two aspergillomas complicating chronic pulmonary aspergillosis were pan-azole resistant. Microsatellite typing was identical for all isolates despite major phenotypic and some growth rate differences. Three different<jats:italic>cyp51A<\/jats:italic>mutations were found (G138C, Y431C, and G434C), of which the first two were demonstrated by heterologous expression in a hypersusceptible<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Saccharomyces cerevisiae<\/jats:named-content>strain to be at least partly responsible for elevated MICs.<jats:italic>cyp51A<\/jats:italic>and<jats:italic>cyp51B<\/jats:italic>gene duplication was excluded, but increased expression of<jats:italic>cyp51A<\/jats:italic>was demonstrated in three isolates selected for additional study (7-to 13-fold increases). In the isolate with the greatest<jats:italic>cyp51A<\/jats:italic>expression, an<jats:italic>Aft1<\/jats:italic>transposon was found inserted 370 bp upstream of the start codon of the<jats:italic>cyp51A<\/jats:italic>gene, an integration location never previously demonstrated in<jats:italic>Aspergillus<\/jats:italic>. Two transcription start sites were identified at 49 and 136 bp upstream of the start codon. The role of the<jats:italic>Aft1<\/jats:italic>transposon, if any, in modulating<jats:italic>cyp51A<\/jats:italic>expression remains to be established. Increased mRNA expression of the transporters<jats:italic>AfuMDR1<\/jats:italic>and<jats:italic>AfuMDR4<\/jats:italic>also was demonstrated in some isolates, which could contribute to azole resistance or simply represent a stress response. The diversity of confirmed and possible azole resistance mechanisms demonstrated in a single series of isogenic isolates is remarkable, indicating the ability of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">A. fumigatus<\/jats:named-content>to adapt in the clinical setting.<\/jats:p>","DOI":"10.1128\/aac.00517-11","type":"journal-article","created":{"date-parts":[[2011,8,30]],"date-time":"2011-08-30T01:47:57Z","timestamp":1314668877000},"page":"5113-5121","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":94,"title":["Interrogation of Related Clinical Pan-Azole-Resistant Aspergillus fumigatus Strains: G138C, Y431C, and G434C Single Nucleotide Polymorphisms in<i>cyp51A<\/i>, Upregulation of<i>cyp51A<\/i>, and Integration and Activation of Transposon<i>Atf1<\/i>in the<i>cyp51A<\/i>Promoter"],"prefix":"10.1128","volume":"55","author":[{"given":"Ahmed M.","family":"Albarrag","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology, College of Medicine and University Hospital, King Saud University, Riyadh, Saudi Arabia"},{"name":"School of Translational Medicine, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Anderson","sequence":"additional","affiliation":[{"name":"School of Translational Medicine, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan J.","family":"Howard","sequence":"additional","affiliation":[{"name":"School of Translational Medicine, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoff D.","family":"Robson","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences, Manchester Academic Health Science Centre, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"Warn","sequence":"additional","affiliation":[{"name":"School of Translational Medicine, Manchester, United Kingdom"},{"name":"University Hospital of South Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Sanglard","sequence":"additional","affiliation":[{"name":"The University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom and Institute of Microbiology, University of Lausanne, and University Hospital Center, Rue de Bugnon 48, CH-1011, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Denning","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, College of Medicine and University Hospital, King Saud University, Riyadh, Saudi Arabia"},{"name":"School of Translational Medicine, Manchester, United Kingdom"},{"name":"Faculty of Life Sciences, Manchester Academic Health Science Centre, Manchester, United Kingdom"},{"name":"University Hospital of South Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.34.1.87-93.1996"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.42.9.4335-4337.2004"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.4.3.625-632.2005"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.36.9.2413-2418.1998"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkq279"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkh507"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.11.4405-4413.2004"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2010.151043.34"},{"key":"e_1_3_3_10_2","volume-title":"Global burden of chronic pulmonary aspergillosis as a sequel to pulmonary tuberculosis.","author":"Denning D. 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