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.; Chanana, Shaurya; Barns, Kenneth; Fossen, Jen; Sanchez, Hiram; Chevrette, Marc G.; Guzei, Ilia A.; Zhao, Changgui; Guo, Le; Tang, Weiping; Currie, Cameron R.; Rajski, Scott R.; Audhya, Anjon; Andes, David R.; Bugni, Tim S. (2020). A marine microbiome antifungal targets urgent-threat drug-resistant fungi. Science (Wash.) 370(6519): 974-978. https://dx.doi.org/10.1126/science.abd6919
In: Science (Washington). American Association for the Advancement of Science: New York, N.Y. ISSN 0036-8075; e-ISSN 1095-9203, meer
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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 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. |
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