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

IF 44.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Science 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

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引用次数: 84

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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一种海洋微生物组抗真菌药物靶向紧急威胁耐药真菌。

迫切需要新的抗真菌药物来解决真菌感染性疾病的出现和跨大陆传播，例如耐药念珠菌。利用海洋动物的微生物组和先进的代谢组学和基因组工具，我们发现了令人鼓舞的具有体内功效的先导抗真菌分子。最有希望的先导物turbinmicin在体外和小鼠模型中对多重耐药真菌病原体显示出强有力的疗效，具有广泛的安全指数，并通过真菌特异性的作用模式起作用，靶向水疱转运途径的Sec14。与其他抗真菌药物不同的有效性，安全性和作用方式使turbinmicin成为一种非常有前途的抗真菌药物，有助于解决破坏性的全球真菌病原体，如C. auris。

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来源期刊

Science 综合性期刊-综合性期刊

CiteScore

61.10

自引率

0.90%

发文量

审稿时长

2.1 months

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