Repositionable Compounds with Antifungal Activity against Multidrug Resistant Candida auris Identified in the Medicines for Malaria Venture’s Pathogen Box
Lopez-Ribot, José L.
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Background. <i>Candida auris</i> has spread rapidly around the world as a causative agent of invasive candidiasis in health care facilities and there is an urgent need to find new options for treating this emerging, often multidrug-resistant pathogen. Methods. We screened the Pathogen Box<sup>®</sup> chemical library for inhibitors of <i>C. auris</i> strain 0390, both under planktonic and biofilm growing conditions. Results. The primary screen identified 12 compounds that inhibited at least 60% of biofilm formation or planktonic growth. After confirmatory dose-response assays, iodoquinol and miltefosine were selected as the two main leading repositionable compounds. Iodoquinol displayed potent in vitro inhibitory activity against planktonic <i>C. auris</i> but showed negligible inhibitory activity against biofilms; whereas miltefosine was able to inhibit the growth of <i>C. auris</i> under both planktonic and biofilm-growing conditions. Subsequent experiments confirmed their activity against nine other strains <i>C. auris</i> clinical isolates, irrespective of their susceptibility profiles against conventional antifungals. We extended our studies further to seven different species of <i>Candida</i>, also with similar findings. Conclusion. Both drugs possess broad spectrum of activity against <i>Candida</i> spp., including multiple strains of the emergent <i>C. auris</i>, and may constitute promising repositionable options for the development of novel therapeutics for the treatment of candidiasis.