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Cell. Infect. Microbiol."],"abstract":"<jats:p>Fungal infection is a serious global health issue, causing approximately 1.5 million mortalities annually. However, clinically available anti-fungal drugs are limited, especially for multidrug-resistant fungal infections. Therefore, new antifungal drugs are urgently needed to address this clinical challenge. In this study, we proposed two non-antifungal drugs, auranofin and pentamidine, in combination to fight against multidrug-resistant <jats:italic>C. albicans<\/jats:italic>. The insufficient antifungal activity of anti-rheumatic drug auranofin is partially due to fungal membrane barrier preventing the drug uptake, and anti-protozoal drug pentamidine was used here to improve the permeability of membrane. The auranofin\/pentamidine combination displayed synergistic inhibitory effect against both drug-susceptible and drug-resistant <jats:italic>C. albicans<\/jats:italic>, as well as biofilm, and significantly reduced the minimum inhibitory concentration of each drug. At non-antifungal concentration, pentamidine can disrupt the membrane integrity and increase membrane permeability, leading to enhanced cellular uptake of auranofin in <jats:italic>C. albicans<\/jats:italic>. This repurposing strategy using the combination of non-antifungal drugs with complementary antifungal mechanism may provide a novel approach for discovery of antifungal drugs to fight against multidrug-resistant fungal infections.<\/jats:p>","DOI":"10.3389\/fcimb.2022.1065962","type":"journal-article","created":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T11:26:52Z","timestamp":1671103612000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Repurposing non-antifungal drugs auranofin and pentamidine in combination as fungistatic antifungal agents against C. albicans"],"prefix":"10.3389","volume":"12","author":[{"given":"Jiaying","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueyi","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijing","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingxiao","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiyan","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sha","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,12,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/j.mimet.2012.09.033","article-title":"In situ potentiometric method to evaluate bacterial outer membrane-permeabilizing ability of drugs: Example using antiprotozoal diamidines","volume":"91","author":"Ando","year":"2012","journal-title":"J. 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