Discovery of broad-spectrum fungicides that block septin-dependent infection processes of pathogenic fungi
| Autor: | Guoshu Gong, Yan Li, Ling Jiang, Míriam Osés-Ruiz, Junjie Yin, Jichun Wang, Mawsheng Chern, Xiaobo Zhu, Guoxiong Peng, Deqiang Li, Yuping Wang, Xiaofang Sun, Xu Youpin, Mingliang Lei, Xia Yan, Bingtian Ma, Fu Huang, Bozeng Tang, Zongkuan Wang, Peng Qin, Qingqing Hou, Jiali Liu, Jing Fan, Xuewei Chen, Iris Eisermann, Lauren S. Ryder, Tuo Qi, Keke Zhu, Chen Jinhua, Xianjun Wu, Jing Wang, Min He, Ping Li, Sin Man Lam, Li Song, Hai Qing, Wenming Wang, Long Wang, Weitao Li, Guanghou Shui, Jia Su, Shigui Li, Xiue Wang, Yuan Luo, Yuyan Cao, Lihuang Zhu, Yuxian Xia, Nicholas J. Talbot |
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| Rok vydání: | 2020 |
| Předmět: |
Microbiology (medical)
Immunology Fungus GTPase Septin Applied Microbiology and Biotechnology Microbiology Fungal Proteins 03 medical and health sciences chemistry.chemical_compound Microbial ecology Biosynthesis Ascomycota Genetics Enzyme Inhibitors 030304 developmental biology Plant Diseases 0303 health sciences Appressorium biology 030306 microbiology fungi Fatty Acids Fungi food and beverages Oryza Cell Biology biology.organism_classification Antimicrobial Fungicides Industrial Fungicide chemistry Septins |
| Zdroj: | Nature microbiology. 5(12) |
| ISSN: | 2058-5276 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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