Screening Repurposing Libraries to Identify Drugs with Novel Antifungal Activity against Candida auris

Candida auris is a fungal opportunistic pathogen that was discovered in 2009 in an ear infection in Japan. It has since spread as a cause of invasive candidiasis across the world. C. auris infections have high mortality rates because of the ability of this fungus to spread easily between patients in healthcare facilities, the difficulty in correctly identifying this organism and accurately diagnosing these infections, and the antifungal resistance displayed by most C. auris strains. New treatment options are clearly needed to address the issues seen with these infections, and here we have chosen a drug repurposing (or repositioning) approach in search for compounds with novel antifungal activity against this emerging pathogen, as repurposing is faster, less costly, and more likely to succeed than de novo discovery. In this project, four drug repurposing libraries were screened in an attempt to find compounds that are effective as potential future antifungals. A screen of the Prestwick Chemical Library identified Ebselen as an effective inhibitor of planktonic growth while a screen of the Pathogen Box identified Iodoquinol as an inhibitor of planktonic growth and Miltefosine as an inhibitor of biofilm formation and planktonic growth, as well as having the ability to reduce pre-formed biofilms. Further investigation was able to also show the broad-spectrum antifungal activity of the three compounds. A screen of the Calibr ReFRAME library and of the Broad Institute Repurposing Hub identified a total of 17 compounds effective in the inhibition of biofilm formation. These results demonstrate that drug repurposing is an effective method for identification of possible future antifungals.