A marine microbiome antifungal targets urgent-threat drug-resistant fungi.
Fan ZhangMiao ZhaoDoug R BraunSpencer S EricksenJeff S PiotrowskiJustin NelsonJian PengGene E AnanievShaurya ChananaKenneth BarnsJen FossenHiram SanchezMarc G ChevretteIlia A GuizeiChanggui ZhaoLe GuoWeiping TangCameron R CurrieScott R RajskiAnjon AudhyaDavid R AndesTim S BugniPublished in: Science (New York, N.Y.) (2021)
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.