Screening a Repurposing Library for Inhibitors of Multidrug-Resistant Candida auris Identifies Ebselen as a Repositionable Candidate for Antifungal Drug Development

Antimicrobial Agents and Chemotherapy
Gina WallJose L Lopez-Ribot

Abstract

Since its original isolation in 2009, Candida auris has spread across the globe as a causative agent of invasive candidiasis. C. auris is typically intrinsically resistant to fluconazole and can also be resistant to echinocandins and even amphotericin B. Thus, there is an urgent need to find new treatment options against this emerging pathogen. To address this growing problem, we performed a screen of the Prestwick Chemical library, a repurposing library of 1,280 small molecules, consisting mostly of approved off-patent drugs, in search of those with activity against a multidrug-resistant C. auris isolate. Our initial screen, using standardized susceptibility testing methodologies, identified nine miscellaneous compounds with no previous clinical indication as antifungals or antiseptics that displayed activity against C. auris Confirmation and follow-up studies identified ebselen as the drug displaying the most potent activity, with 100% inhibition of growth detected at concentrations as low as 2.5 μM. We further evaluated the ability of ebselen to inhibit C. auris biofilm formation and examined the effects of combination therapies of ebselen with clinically used antifungals. We extended our studies to different C. auris strain...Continue Reading

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Citations

Oct 28, 2019·Current Topics in Medicinal Chemistry·Laura Nunes SilvaAndré Luis Souza Dos Santos
May 1, 2020·FEMS Yeast Research·Dongmei LiRichard Calderone
Jul 15, 2020·Antimicrobial Agents and Chemotherapy·Gina Wall, Jose L Lopez-Ribot
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Jul 30, 2020·Antibiotics·Gina Wall, Jose L Lopez-Ribot
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Dec 17, 2020·Frontiers in Cellular and Infection Microbiology·Gina WallJose L Lopez-Ribot
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