Discovery of broad-spectrum fungicides that block septin-dependent infection processes of pathogenic fungi
Discovery of broad-spectrum fungicides that block septin-dependent infection processes of pathogenic fungi
复制标题
发现可阻断病原真菌依赖于败血症的感染过程的广谱杀菌剂
DOI：
10.1038/s41564-020-00790-y
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发表时间：
2020-09-21
影响因子：
28.3
通讯作者：
Chen, Xuewei
中科院分区：
文献类型：
--
作者：
He, Min;Su, Jia;Chen, Xuewei
许多致病真菌依靠称为附着胞的特殊感染结构的发展来入侵宿主并引起疾病。因此，破坏真菌感染结构的功能提供了一种预防疾病的潜在手段。然而，尽管有这种非凡的潜力，用于控制植物或动物真菌疾病的抗渗透药物却相对较少。在目前的研究中，我们报告了鉴定的化合物，专门防止真菌感染。我们发现稻瘟病真菌magnaporthe oryzae在附着胞介导的侵染中所必需的septin gtp酶的组织需要超长链脂肪酸（VLCFAs），而VLCFAs是膜界面septin组织的介质。VLCFAs促进隔层蛋白募集到弯曲的质膜，VLCFAs的耗尽阻止隔层蛋白的组装和宿主渗透。oryzae。研究发现，VLCFA生物合成抑制剂不仅可以预防稻瘟病，而且对玉米、小麦和蝗虫的多种真菌病原体都有有效的广谱杀真菌活性，而不影响其各自的宿主。我们的发现揭示了真菌中septin介导的感染结构形成的机制，并为控制植物和动物的各种疾病提供了一类杀菌剂。
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 fungusMagnaporthe 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 byM. 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.