Discovery of broad-spectrum fungicides that block septin-dependent infection processes of pathogenic fungi

He, Min, Su, Jia, Xu, Youpin, Chen, Jinhua, Chern, Mawsheng, Lei, Mingliang, Qi, Tuo, Wang, Zongkuan, Ryder, Lauren S., Tang, Bozeng, Osés-Ruiz, Míriam, Zhu, Keke, Cao, Yuyan, Yan, Xia, Eisermann, Iris, Luo, Yuan, Li, Weitao, Wang, Jing, Yin, Junjie, Lam, Sin Man, Peng, Guoxiong, Sun, Xiaofang, Zhu, Xiaobo, Ma, Bingtian, Wang, Jichun, Liu, Jiali, Qing, Hai, Song, Li, Wang, Long, Hou, Qingqing, Qin, Peng, Li, Yan, Fan, Jing, Li, Deqiang, Wang, Yuping, Wang, Xiue, Jiang, Ling, Shui, Guanghou, Xia, Yuxian, Gong, Guoshu, Huang, Fu, Wang, Wenming, Wu, Xianjun, Li, Ping, Zhu, Lihuang, Li, Shigui, Talbot, Nicholas J. ORCID: and Chen, Xuewei (2020) Discovery of broad-spectrum fungicides that block septin-dependent infection processes of pathogenic fungi. Nature Microbiology, 5 (12). pp. 1565-1575. ISSN 2058-5276

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Many pathogenic fungi depend on the development of specialized infection structures called appressoria to invade their hosts and cause disease. Impairing the function of fungal infection structures therefore provides a potential means by which diseases could be prevented. In spite of this extraordinary potential, however, relatively few anti-penetrant drugs have been developed to control fungal diseases, of either plants or animals. In the present study, we report the identification of compounds that act specifically to prevent fungal infection. We found that the organization of septin GTPases, which are essential for appressorium-mediated infection in the rice blast fungus Magnaporthe oryzae, requires very-long-chain fatty acids (VLCFAs), which act as mediators of septin organization at membrane interfaces. VLCFAs promote septin recruitment to curved plasma membranes and depletion of VLCFAs prevents septin assembly and host penetration by M. oryzae. We observed that VLCFA biosynthesis inhibitors not only prevent rice blast disease, but also show effective, broad-spectrum fungicidal activity against a wide range of fungal pathogens of maize, wheat and locusts, without affecting their respective hosts. Our findings reveal a mechanism underlying septin-mediated infection structure formation in fungi and provide a class of fungicides to control diverse diseases of plants and animals.

Item Type: Article
Uncontrolled Keywords: microbiology,immunology,applied microbiology and biotechnology,genetics,microbiology (medical),cell biology ,/dk/atira/pure/subjectarea/asjc/2400/2404
Faculty \ School: Faculty of Science > The Sainsbury Laboratory
Faculty of Science > School of Environmental Sciences
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Centres > Norwich Institute for Healthy Aging
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Depositing User: LivePure Connector
Date Deposited: 25 Feb 2021 00:57
Last Modified: 25 Oct 2023 01:38
DOI: 10.1038/s41564-020-00790-y

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