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.

许多致病真菌依赖于称为附着菌的特殊感染结构的发展来侵入宿主并引起疾病。因此，削弱真菌感染结构的功能提供了一种可以预防疾病的潜在手段。然而，尽管具有这种非凡的潜力，但开发用于控制植物或动物真菌疾病的抗渗透药物相对较少。在本研究中，我们报告了特异性预防真菌感染的化合物的鉴定。我们发现 septin GTPases 的组织，这对稻瘟病真菌Magnaporthe oryzae 中附着胞介导的感染至关重要, 需要超长链脂肪酸 (VLCFA)，它们在膜界面充当隔膜组织的介质。VLCFAs促进的Septin募集至弯曲质膜和VLCFAs防止的Septin组件和主机渗透通过的耗尽稻瘟病菌。我们观察到 VLCFA 生物合成抑制剂不仅可以预防稻瘟病，而且对玉米、小麦和蝗虫等多种真菌病原体表现出有效的广谱杀真菌活性，而不会影响它们各自的宿主。我们的研究结果揭示了真菌中 septin 介导的感染结构形成的潜在机制，并提供了一类杀菌剂来控制植物和动物的各种疾病。