Description:

Marine-invertebrate associated bacteria as a source of new antifungal agents

Fungal infections are a growing health problem worldwide and are the number one cause of infectious disease in cancer and organ transplant patients. There are only three classes of antifungals that are effective for systemic disease and mortality rates remain exceedingly high. For multi-drug resistant fungal pathogens, mortality rates exceed 80%. Therefore, there is a critical need for new antifungal agents. To address this need, we have leveraged the chemical diversity of marine bacterial natural products combined with an innovative discovery platform. After screening large natural product libraries, we have identified a large number of hits with in vitro activity against multi-drug resistant fungal pathogens. We are using yeast chemical genomics and MSMS for a combined structure/function hit prioritization scheme. For chemical genomics, we use a yeast DNA-barcoded knockout library to identify antifungals that likely have a different mechanism of action from clinically used antifungals. For MSMS, we are using new tools that provide structural information even for unknown molecules. This presentation will focus on antifungals discovered from this pipeline as well as the hit prioritization strategy.