{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:31:44Z","timestamp":1790685104555,"version":"4.1.0"},"reference-count":55,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,10,17]],"date-time":"2020-10-17T00:00:00Z","timestamp":1602892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondo de Investigacion Sanitaria.","award":["FIS PI18CIII\/00045"],"award-info":[{"award-number":["FIS PI18CIII\/00045"]}]},{"name":"Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirecci\u00f3n General de Redes y Centros de Investigaci\u00f3n Cooperativa, Ministerio de Econom\u00eda, Industria y Competitividad, Spanish Network for Research in Infectious Diseases","award":["REIPI RD16\/CIII\/0004\/0003"],"award-info":[{"award-number":["REIPI RD16\/CIII\/0004\/0003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Infections caused by Aspergillus species are being increasingly reported. Aspergillus flavus is the second most common species within this genus causing invasive infections in humans, and isolates showing azole resistance have been recently described. A. flavus has three cyp51-related genes (cyp51A, cyp51B, and cyp51C) encoding 14-\u03b1 sterol demethylase-like enzymes which are the target of azole drugs. In order to study triazole drug resistance in A. flavus, three strains showing reduced azole susceptibility and 17 azole susceptible isolates were compared. The three cyp51-related genes were amplified and sequenced. A comparison of the deduced Cyp51A, Cyp51B, and Cyp51C protein sequences with other protein sequences from orthologous genes in different filamentous fungi led to a protein identity that ranged from 50% to 80%. Cyp51A and Cyp51C presented several synonymous and non-synonymous point mutations among both susceptible and non-susceptible strains. However, two amino acid mutations were present only in two resistant isolates: one strain harbored a P214L substitution in Cyp51A, and another a H349R in Cyp51C that also showed an increase of cyp51A and cyp51C gene expression compared to the susceptible strain ATCC2004304. Isolates that showed reduced in vitro susceptibility to clinical azoles exhibited a different susceptibility profile to demethylation inhibitors (DMIs). Although P214L substitution might contribute to azole resistance, the role of H349R substitution together with changes in gene expression remains unclear.<\/jats:p>","DOI":"10.3390\/genes11101217","type":"journal-article","created":{"date-parts":[[2020,10,17]],"date-time":"2020-10-17T05:45:51Z","timestamp":1602913551000},"page":"1217","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Point Mutations in the 14-\u03b1 Sterol Demethylase Cyp51A or Cyp51C Could Contribute to Azole Resistance in Aspergillus flavus"],"prefix":"10.3390","volume":"11","author":[{"given":"Jose","family":"Lucio","sequence":"first","affiliation":[{"name":"Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III (ISCIII), Majadahonda, 28220 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4821-4852","authenticated-orcid":false,"given":"Irene","family":"Gonzalez-Jimenez","sequence":"additional","affiliation":[{"name":"Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III (ISCIII), Majadahonda, 28220 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Rivero-Menendez","sequence":"additional","affiliation":[{"name":"Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III (ISCIII), Majadahonda, 28220 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8651-4405","authenticated-orcid":false,"given":"Ana","family":"Alastruey-Izquierdo","sequence":"additional","affiliation":[{"name":"Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III (ISCIII), Majadahonda, 28220 Madrid, Spain"},{"name":"Spanish Network for Research in Infectious Diseases (REIPI RD16\/CIII\/0004\/0003), ISCIII, Majadahonda, 28220 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Pelaez","sequence":"additional","affiliation":[{"name":"Hospital Universitario Central de Asturias, Fundaci\u00f3n para la Investigaci\u00f3n Biosanitaria del Principado de Asturias (FINBA), Oviedo, 33011 Asturias, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Alcazar-Fuoli","sequence":"additional","affiliation":[{"name":"Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III (ISCIII), Majadahonda, 28220 Madrid, Spain"},{"name":"Spanish Network for Research in Infectious Diseases (REIPI RD16\/CIII\/0004\/0003), ISCIII, Majadahonda, 28220 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9801-0260","authenticated-orcid":false,"given":"Emilia","family":"Mellado","sequence":"additional","affiliation":[{"name":"Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III (ISCIII), Majadahonda, 28220 Madrid, Spain"},{"name":"Spanish Network for Research in Infectious Diseases (REIPI RD16\/CIII\/0004\/0003), ISCIII, Majadahonda, 28220 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/j.1469-0691.2008.01978.x","article-title":"Changing epidemiology of systemic fungal infections","volume":"14","author":"Richardson","year":"2008","journal-title":"Clin. 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