{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:31:35Z","timestamp":1790685095622,"version":"4.1.0"},"reference-count":83,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,11,26]],"date-time":"2020-11-26T00:00:00Z","timestamp":1606348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Salud Carlos III. Fondo de Investigacion Sanitaria","award":["FIS PI18CIII\/00045"],"award-info":[{"award-number":["FIS PI18CIII\/00045"]}]},{"name":"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":["JoF"],"abstract":"<jats:p>The emergence and spread of Aspergillus fumigatus azole resistance has been acknowledged worldwide. The main problem of azole resistance is the limited therapeutic options for patients suffering aspergillosis. Azole resistance mechanisms have been mostly linked to the enzyme Cyp51A, a target of azole drugs, with a wide variety of modifications responsible for the different resistance mechanisms described to date. However, there are increasing reports of A. fumigatus strains showing azole resistance without Cyp51A modifications, and thus, novel resistance mechanisms are being explored. Here, we characterized two isogenic A. fumigatus clinical strains isolated two years apart from the same patient. Both strains were resistant to clinical azoles but showed different azole resistance mechanisms. One strain (CM8940) harbored a previously described G54A mutation in Cyp51A while the other strain (CM9640) had a novel G457S mutation in Cyp51B, the other target of azoles. In addition, this second strain had a F390L mutation in Hmg1. CM9640 showed higher levels of gene expression of cyp51A, cyp51B and hmg1 than the CM8940 strain. The role of the novel mutation found in Cyp51B together with the contribution of a mutation in Hmg1 in azole resistance is discussed.<\/jats:p>","DOI":"10.3390\/jof6040315","type":"journal-article","created":{"date-parts":[[2020,11,26]],"date-time":"2020-11-26T09:04:15Z","timestamp":1606381455000},"page":"315","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["A Cyp51B Mutation Contributes to Azole Resistance in Aspergillus fumigatus"],"prefix":"10.3390","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4821-4852","authenticated-orcid":false,"given":"Irene","family":"Gonzalez-Jimenez","sequence":"first","affiliation":[{"name":"Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III (ISCIII), Majadahonda, 28222 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7545-7510","authenticated-orcid":false,"given":"Jose","family":"Lucio","sequence":"additional","affiliation":[{"name":"Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III (ISCIII), Majadahonda, 28222 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8987-5115","authenticated-orcid":false,"given":"Jorge","family":"Amich","sequence":"additional","affiliation":[{"name":"Manchester Fungal Infection Group (MFIG), Division of Infection, Immunity and Respiratory Medicine, University of Manchester, Manchester M13 9PL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Cuesta","sequence":"additional","affiliation":[{"name":"Bioinformatics Unit, Common Scientific Technical Units, Instituto de Salud Carlos III (ISCIII), Majadahonda, 28222 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Sanchez Arroyo","sequence":"additional","affiliation":[{"name":"Microbiology Laboratory, Hospital de \u00c1vila, 05004 \u00c1vila, 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, 28222 Madrid, Spain"},{"name":"Spanish Network for Research in Infectious Diseases (REIPI RD16\/CIII\/0004\/0003), Instituto de Salud Carlos III (ISCIII), Majadahonda, 28222 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, 28222 Madrid, Spain"},{"name":"Spanish Network for Research in Infectious Diseases (REIPI RD16\/CIII\/0004\/0003), Instituto de Salud Carlos III (ISCIII), Majadahonda, 28222 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e00140-18","DOI":"10.1128\/CMR.00140-18","article-title":"Aspergillus fumigatus and Aspergillosis in 2019","volume":"33","author":"Chamilos","year":"2019","journal-title":"Clin. 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