Identification of novel antifungal activity in Prestwick Chemical Library against Candida albicans biofilms




Siles, Samuel A.

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Candida albicans is the most common cause of systemic fungal infections with unacceptably high mortality rates. The existing arsenal of antifungal drugs is very limited, and is particularly ineffective against C. albicans biofilms. To address this problem, I screened a small molecule library consisting of 1200 FDA approved drugs, the Prestwick Chemical Library, for novel antifungal activity against C. albicans SC5314 biofilms. Using a 96-well high-throughput screening assay, I identified 38 compounds to be effective in preventing the formation of biofilms from planktonic cells, and these compounds were further tested for their efficacy against preformed biofilms. These compounds were classified as antifungal drugs, or as antimicrobials/antiseptics or as multifunctional drugs, which are drugs with no previously antifungal activity. The antimicrobial/antiseptic and multifunctional drugs that were most effective against preformed biofilms of C. albicans SC5314 were also found to be equally effective against three clinical isolates of C. albicans 412, 2307, and 6482. Thus, repurposing FDA-approved drugs opens up a valuable new avenue for the development of novel antifungal drugs.


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Integrative Biology