背景回顾：Plant diseases cause a huge impact on food security and are of global concern. While application of agrochemicals is a common approach in the control of plant diseases currently, growing drug resistance and the impact of off-target effects of these compounds pose major challenges. The identification of pathogenicity-related virulence mechanisms and development of new chemicals that target these processes are urgently needed. One such virulence mechanism is the detoxification of reactive oxygen species (ROS) generated by host plants upon attack by pathogens.

提出问题：The machinery of ROS detoxification might therefore serve as a drug target for preventing plant diseases, but few anti-ROS-scavenging drugs have been developed. 

主要发现：Here, we show that in the model system Botrytis cinerea secretion of the cytochrome c-peroxidase, BcCcp1 removes plant-produced H2O2 and promotes pathogen invasion. 

结果1-BcTol1-BcCCp1：The peroxidase secretion is modulated by a Tom1-like protein, BcTol1, through physical interaction. We show that BcTol1 is regulated at different levels to enhance the secretion of BcCcp1 during the early infection stage. 

结果2-功能验证：Inactivation of either BcTol1 or BcCcp1 leads to dramatically reduced virulence of B. cinerea. 

结果3-广靶抗性：We identify two BcTol1-targeting small molecules that not only prevent B. cinerea invasion but also have effective activity against a wide range of plant fungal pathogens without detectable effect on the hosts. 

结论：These findings reveal a conserved mechanism of ROS detoxification in fungi and provide a class of potential fungicides to control diverse plant diseases. The approach described here has wide implications for further drug discovery in related fields. 

 摘 要 

植物病害会导致食物安全受到威胁，是全球关注的重点。虽然通过农用化学品的施用是目前普遍用来控制植物病虫害的常用方法，但是日益增长的耐药性以及这些化学药物的非靶向效应正导致越来越严峻的挑战。鉴定病原菌相关的毒力机制以及开发新的化学药物靶向这些致毒进程变得越来越重要。其中一个毒力机制是寄主植物在遭受病原菌攻击时，会诱导产生活性氧物质（ROS）来解毒。ROS解毒因此可以作为一个药物靶向进程，用来预防植物疾病，但是目前已开发的抗活性氧清除剂比较少。本文中，作者发现模式系统灰霉菌Botrytis cinerea分泌的细胞色素c-过氧化物酶BcCcp1能够清除植物中产生的过氧化氢，从而促进病原菌的侵染。过氧化物酶的分泌可以被一个Tom1-like蛋白BcTol1通过物理互作的方式进行调控。作者发现BcTol1在不同的水平上被调控，以增强早期侵染阶段的BcCcp1分泌。无论是BcTol1或者BcCcp1的失活都会导致灰霉菌的毒力严重下降。另外，作者还鉴定到了2个BcTol1靶向的小分子，不仅可以防止灰霉菌的侵染，还可以对一系列的植物真菌性病原菌具有抗性作用，而对寄主植物的影响微乎其微。本文的研究揭示了一个真菌中保守的ROS解毒机制，并且为控制植物疾病提供了潜在的杀菌剂。本文所报道的方法具有潜在应用价值，为进一步的药物开发提供信息。

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