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真菌对免疫的逃避涉及阻断组织蛋白酶介导的危险感应蛋白酶的切割成熟。

Fungal evasion of immunity involves blocking the cathepsin-mediated cleavage maturation of the danger-sensing protease.

作者信息

Tang Guirong, Song Shuangxiu, Shang Junmei, Luo Yujuan, Li Shiqin, Wei Dongxiang, Wang Chengshu

机构信息

Key Laboratory of Insect Developmental and Evolutionary Biology, CAS Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai 200032, China.

Institute of Edible Fungi, Shanghai Academy of Agricultural Sciences, Shanghai 201106, China.

出版信息

Proc Natl Acad Sci U S A. 2025 Jan 21;122(3):e2419343122. doi: 10.1073/pnas.2419343122. Epub 2025 Jan 16.

DOI:10.1073/pnas.2419343122
PMID:39819219
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11760918/
Abstract

Entomopathogenic fungi play a critical role in regulating insect populations, and representative species from the and genera have been developed as eco-friendly biocontrol agents for managing agricultural insect pests. Relative to the advances in understanding antifungal immune responses in , knowledge of how fungi evade insect immune defenses remains limited. In this study, we report the identification and characterization of a virulence-required effector Fkp1 in . Library screening and protein pull-down analysis unveiled that Fkp1 targets the cathepsin protease CtsK1 to inhibit its cleavage maturation of the danger-sensing serine protease Persephone (Psh), thereby facilitating fungal evasion of the immune defenses. The -like gene is also required in for insect infection. Transgenic expression of in suppressed hemolymph cysteine protease activity and down-regulated the expression of antifungal genes. Fkp1 can also mask the Psh cleavage site without interfering with its ability to bait fungal subtilisin proteases. Given the evident compensatory relationship, our data indicate that the protease cascade is more crucial than the molecular pattern pathway in defending flies against fungal infections. This work reveals that fungi have evolved distinct effectors to block the dual recognition pathways of flies for immune evasion and sheds lights on the effector mechanisms mediating microbe-animal interactions.

摘要

昆虫病原真菌在调节昆虫种群数量方面发挥着关键作用,来自[具体属名1]和[具体属名2]属的代表性物种已被开发为用于防治农业害虫的生态友好型生物防治剂。相对于在了解[昆虫物种名1]抗真菌免疫反应方面的进展,关于真菌如何逃避昆虫免疫防御的知识仍然有限。在本研究中,我们报告了[昆虫物种名2]中一种毒力必需效应子Fkp1的鉴定和表征。文库筛选和蛋白质下拉分析表明,Fkp1靶向组织蛋白酶CtsK1以抑制其对危险感知丝氨酸蛋白酶珀尔塞福涅(Psh)的切割成熟,从而促进真菌逃避[昆虫物种名2]的免疫防御。在[昆虫物种名2]中感染昆虫也需要类似[Fkp1的基因名称]的基因。在[昆虫物种名2]中转基因表达[Fkp1的基因名称]可抑制血淋巴半胱氨酸蛋白酶活性并下调抗真菌基因的表达。Fkp1还可以掩盖Psh的切割位点,而不干扰其诱饵真菌枯草杆菌蛋白酶的能力。鉴于明显的补偿关系,我们的数据表明蛋白酶级联反应在保护果蝇免受真菌感染方面比分子模式途径更为关键。这项工作揭示了[昆虫物种名2]真菌已经进化出不同的效应子来阻断果蝇的双重识别途径以实现免疫逃避,并阐明了介导微生物与动物相互作用的效应子机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0a8/11760918/52a359a00429/pnas.2419343122fig05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0a8/11760918/c94836a91ed6/pnas.2419343122fig01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0a8/11760918/ef5424258903/pnas.2419343122fig02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0a8/11760918/43a35a8480d8/pnas.2419343122fig03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0a8/11760918/56d4d1128043/pnas.2419343122fig04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0a8/11760918/52a359a00429/pnas.2419343122fig05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0a8/11760918/c94836a91ed6/pnas.2419343122fig01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0a8/11760918/ef5424258903/pnas.2419343122fig02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0a8/11760918/43a35a8480d8/pnas.2419343122fig03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0a8/11760918/56d4d1128043/pnas.2419343122fig04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0a8/11760918/52a359a00429/pnas.2419343122fig05.jpg

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