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However, drug\u2010drug interactions caused by azoles inhibiting the human CYP3A4 enzyme, together with increasing resistance of\n                    <jats:italic>Candida<\/jats:italic>\n                    species to azoles, represent serious issues with this class of drug, making it imperative to develop innovative antifungal drugs to tackle this growing clinical challenge. A drug repurposing approach is used to examine a library of Food and Drug Administration (FDA)\u2010approved drugs, ultimately identifying otilonium bromide (OTB) as an exceptionally encouraging antifungal agent. Mechanistically, OTB impairs vesicle\u2010mediated trafficking by targeting Sec31, thereby impeding the plasma membrane (PM) localization of the ergosterol transporters, such as Sip3. Consequently, OTB obstructs the movement of ergosterol across membranes and triggers cytotoxic autophagy. It is noteworthy that\n                    <jats:italic>C. albicans<\/jats:italic>\n                    encounters challenges in developing resistance to OTB because it is not a substrate for drug transporters. This study opens a new door for antifungal therapy, wherein OTB disrupts ergosterol subcellular distribution and induces cytotoxic autophagy. Additionally, it circumvents the hepatotoxicity associated with azole\u2010mediated liver enzyme inhibition and avoids export\u2010mediated drug resistance in\n                    <jats:italic>C. albicans<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1002\/advs.202406473","type":"journal-article","created":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T10:34:57Z","timestamp":1720780497000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Otilonium Bromide Exhibits Potent Antifungal Effects by Blocking Ergosterol Plasma Membrane Localization and Triggering Cytotoxic Autophagy in\n                    <i>Candida Albicans<\/i>"],"prefix":"10.1002","volume":"11","author":[{"given":"Cheng","family":"Zhen","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Shanghai Tenth People's Hospital School of Medicine Tongji University  No.1239 Siping Road Shanghai 200092 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shanghai Tenth People's Hospital School of Medicine Tongji University  No.1239 Siping Road Shanghai 200092 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanru","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shanghai Tenth People's Hospital School of Medicine Tongji University  No.1239 Siping Road Shanghai 200092 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malcolm","family":"Whiteway","sequence":"additional","affiliation":[{"name":"Department of Biology Concordia University  Montreal QC H4B 1R6 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sijin","family":"Hang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shanghai Tenth People's Hospital School of Medicine Tongji University  No.1239 Siping Road Shanghai 200092 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhua","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shanghai Tenth People's Hospital School of Medicine Tongji University  No.1239 Siping Road Shanghai 200092 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8422-0427","authenticated-orcid":false,"given":"Hui","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shanghai Tenth People's Hospital School of Medicine Tongji University  No.1239 Siping Road Shanghai 200092 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanying","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shanghai Tenth People's Hospital School of Medicine Tongji University  No.1239 Siping Road Shanghai 200092 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,12]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2023.114960"},{"key":"e_1_2_9_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(23)00692-8"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2020.104240"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1586\/14787210.2015.1032939"},{"key":"e_1_2_9_4_1","doi-asserted-by":"crossref","DOI":"10.1128\/mbio.01353-23","volume":"14","author":"Choy H. 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