{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T17:11:19Z","timestamp":1788628279694,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.pntd.0012623","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T00:00:00Z","timestamp":1743552000000}}],"reference-count":60,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T00:00:00Z","timestamp":1743033600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"crossref","award":["JP21jm0510005"],"award-info":[{"award-number":["JP21jm0510005"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Bio-Resource Project, Japan","award":["NBRP-028"],"award-info":[{"award-number":["NBRP-028"]}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>\nBackground\n<\/jats:title>\n<jats:p>Mycetoma is a deep fungal infection caused by several microorganisms, with <jats:italic>Madurella mycetomatis<\/jats:italic> being the most common causative agent. Another related species, <jats:italic>Madurella fahalii<\/jats:italic>, is also known to cause eumycetoma. However, unlike <jats:italic>M. mycetomatis<\/jats:italic>, <jats:italic>M. fahalii<\/jats:italic> exhibits resistance to itraconazole, the standard treatment for eumycetoma, and the underlying cause of this resistance remains unknown. Therefore, understanding the mechanism of this resistance is critical for developing more effective therapies.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>\nPrincipal Findings\n<\/jats:title>\n<jats:p>Using the high-quality draft genome sequence of <jats:italic>Madurella fahalii<\/jats:italic> IFM 68171, we identified two copies of the gene encoding cytochrome P450 14-\u03b1 sterol demethylase (CYP51), the target enzyme of itraconazole. These include a gene conserved among <jats:italic>Madurella<\/jats:italic> species (<jats:italic>Mfcyp51A1<\/jats:italic>) and a <jats:italic>M. fahalii<\/jats:italic>-specific gene (<jats:italic>Mfcyp51A2<\/jats:italic>). Both genes are actively transcribed in <jats:italic>M. fahalii<\/jats:italic> and are upregulated in response to itraconazole. Furthermore, heterologous expression in <jats:italic>Saccharomyces cerevisiae<\/jats:italic> revealed that transformants carrying the <jats:italic>Mfcyp51A2<\/jats:italic> gene exhibited reduced susceptibility to itraconazole compared to those with <jats:italic>Mfcyp51A1.<\/jats:italic><\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>\nConclusion\n<\/jats:title>\n<jats:p>We demonstrated that itraconazole resistance in <jats:italic>M. fahalii<\/jats:italic> may be attributed to the presence of an additional CYP51 gene. This study represents the first report on the physiological characteristics of <jats:italic>Madurella<\/jats:italic> species using genetic engineering techniques.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pntd.0012623","type":"journal-article","created":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T18:48:24Z","timestamp":1743101304000},"page":"e0012623","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Itraconazole resistance in Madurella fahalii linked to a distinct homolog of the gene encoding cytochrome P450 14-\u03b1 sterol demethylase (CYP51)"],"prefix":"10.1371","volume":"19","author":[{"given":"Isato","family":"Yoshioka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed 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