High-throughput screening of mangrove-associated fungal extracts against pathogenic Candida albicans.

Alison H. Hughes

Bill J. Baker

Department of Chemistry and Center for Drug Discovery and Innovation, University of South Florida, Tampa, FL 33620

Candida spp. are the 4^th leading cause of nosocomial bloodstream infections in the United States, with approximately 46,000 cases per year. C. albicans is part of our natural microbiome that live symbiotically within us, and thus drug resistance is prevalent when opportunity allows this yeast to manifest into infection. As their long evolution has shown, microorganisms are far more adroit at competing amongst each other than we have ever been. With that in mind, we aim to screen a library of crude extracts obtained from Floridian mangrove-associated fungi. It is believed that cryptic genes within these fungi are responsible for their production of defensive secondary metabolites in response to stressors in the environment. Our lab has developed a method of culturing fungi on media treated with epigenetic modifiers to create three distinct extracts from each fungus, which has led to the compilation of a library of ~9000 extracts. This screening programme aims to determine activity of fungal crude extracts against a panel of 14 standardized drug-resistant C. albicans strains, obtained from the American Type Culture Collection (ATCC). Procurement of the compound(s) responsible for activity will be achieved using both Nuclear Magnetic Resonance (NMR) and bioassay-guided isolation. Pure compounds will be tested to determine a Minimum Inhibitor Concentration (MIC), as well as testing if the compound works as a fungistatic or fungicidal treatment. Additional studies will include testing for a response against yeast biofilms, mechanism of action, and cytotoxicity.