A marine microbiome antifungal targets urgent-threat drug-resistant fungi.

Zhang, Fan; Zhao, Miao; Braun, Doug R; Ericksen, Spencer S; Piotrowski, Jeff S; Nelson, Justin; Peng, Jian; Ananiev, Gene E et al. · Science · 2020

basic_science · Level V

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Abstract

New antifungal drugs are urgently needed to address the emergence and transcontinental spread of fungal infectious diseases, such as pandrug-resistant <i>Candida auris.</i> Leveraging the microbiomes of marine animals and cutting-edge metabolomics and genomic tools, we identified encouraging lead antifungal molecules with in vivo efficacy. The most promising lead, turbinmicin, displays potent in vitro and mouse-model efficacy toward multiple-drug-resistant fungal pathogens, exhibits a wide safety index, and functions through a fungal-specific mode of action, targeting Sec14 of the vesicular trafficking pathway. The efficacy, safety, and mode of action distinct from other antifungal drugs make turbinmicin a highly promising antifungal drug lead to help address devastating global fungal pathogens such as <i>C. auris.</i>

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