{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:21:51Z","timestamp":1790266911029,"version":"4.1.0"},"reference-count":42,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T00:00:00Z","timestamp":1614211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Aspergillus flavus is a pathogenic fungal species that can cause pulmonary aspergillosis, and triazole compounds are used for the treatment of these infections. Prolonged exposure to azoles may select for compensatory mutations in the A. flavus genome, resulting in azole resistance. Here, we characterize a series of 11 isogenic A. flavus strains isolated from a patient with pulmonary aspergillosis. Over a period of three months, the initially azole-susceptible strain developed itraconazole and voriconazole resistance. Short tandem repeat analysis and whole-genome sequencing revealed the high genetic relatedness of all isolates, indicating an infection with one single isolate. In contrast, the isolates were macroscopically highly diverse, suggesting an adaptation to the environment due to (epi)genetic changes. The whole-genome sequencing of susceptible and azole-resistant strains showed a number of mutations that might be associated with azole resistance. The majority of resistant strains contain a Y119F mutation in the Cyp51A gene, which corresponds to the Y121F mutation found in A. fumigatus. One azole-resistant strain demonstrated a divergent set of mutations, including a V99A mutation in a major facilitator superfamily (MSF) multidrug transporter (AFLA 083950).<\/jats:p>","DOI":"10.3390\/jof7030164","type":"journal-article","created":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T02:08:17Z","timestamp":1614305297000},"page":"164","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Genetic and Phenotypic Characterization of in-Host Developed Azole-Resistant Aspergillus flavus Isolates"],"prefix":"10.3390","volume":"7","author":[{"given":"Jochem B.","family":"Buil","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"},{"name":"Center of Expertise in Mycology Radboudumc\/CWZ, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4893-4438","authenticated-orcid":false,"given":"Jos","family":"Houbraken","sequence":"additional","affiliation":[{"name":"Westerdijk Fungal Biodiversity Institute, 3584 CT Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4401-5103","authenticated-orcid":false,"given":"Monique H.","family":"Reijers","sequence":"additional","affiliation":[{"name":"Center of Expertise in Mycology Radboudumc\/CWZ, 6525 GA Nijmegen, The Netherlands"},{"name":"Department of Pulmonology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2155-7935","authenticated-orcid":false,"given":"Jan","family":"Zoll","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"},{"name":"Center of Expertise in Mycology Radboudumc\/CWZ, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9780-7059","authenticated-orcid":false,"given":"Maurizio","family":"Sanguinetti","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"},{"name":"Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3253-6080","authenticated-orcid":false,"given":"Jacques F.","family":"Meis","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"},{"name":"Center of Expertise in Mycology Radboudumc\/CWZ, 6525 GA Nijmegen, The Netherlands"},{"name":"Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital (CWZ), 6532 SZ Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8600-9860","authenticated-orcid":false,"given":"Paul. E.","family":"Verweij","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"},{"name":"Center of Expertise in Mycology Radboudumc\/CWZ, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5446-2230","authenticated-orcid":false,"given":"Willem J.G.","family":"Melchers","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"},{"name":"Center of Expertise in Mycology Radboudumc\/CWZ, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1183\/13993003.00583-2015","article-title":"Chronic pulmonary aspergillosis: Rationale and clinical guidelines for diagnosis and management","volume":"47","author":"Denning","year":"2016","journal-title":"Eur. 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