Science ( IF 41.845 ) Pub Date : 2020-11-20 , DOI: 10.1126/science.abd6919 Fan Zhang, Miao Zhao, Doug R. Braun, Spencer S. Ericksen, Jeff S. Piotrowski, Justin Nelson, Jian Peng, Gene E. Ananiev, Shaurya Chanana, Kenneth Barns, Jen Fossen, Hiram Sanchez, Marc G. Chevrette, Ilia A. Guzei, Changgui Zhao, Le Guo, Weiping Tang, Cameron R. Currie, Scott R. Rajski, Anjon Audhya, David R. Andes, Tim S. Bugni
New antifungal drugs are urgently needed to address the emergence and transcontinental spread of fungal infectious diseases, such as pandrug-resistant Candida auris. 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 C. auris.