Rohde John R, Breitkreutz Ashton, Chenal Alexandre, Sansonetti Philippe J, Parsot Claude
Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, 28 rue du Dr. Roux, F-75724 Paris, Cédex 15, France.
Cell Host Microbe. 2007 Mar 15;1(1):77-83. doi: 10.1016/j.chom.2007.02.002.
Many bacteria pathogenic for plants or animals, including Shigella spp., which is responsible for shigellosis in humans, use a type III secretion apparatus to inject effector proteins into host cells. Effectors alter cell signaling and host responses induced upon infection; however, their precise biochemical activities have been elucidated in very few cases. Utilizing Saccharomyces cerevisiae as a surrogate host, we show that the Shigella effector IpaH9.8 interrupts pheromone response signaling by promoting the proteasome-dependent destruction of the MAPKK Ste7. In vitro, IpaH9.8 displayed ubiquitin ligase activity toward ubiquitin and Ste7. Replacement of a Cys residue that is invariant among IpaH homologs of plant and animal pathogens abolished the ubiquitin ligase activity of IpaH9.8. We also present evidence that the IpaH homolog SspH1 from Salmonella enterica can ubiquitinate ubiquitin and PKN1, a previously identified SspH1 interaction partner. This study assigns a function for IpaH family members as E3 ubiquitin ligases.
许多对植物或动物致病的细菌，包括导致人类志贺氏菌病的志贺氏菌属，利用III型分泌装置将效应蛋白注入宿主细胞。效应蛋白会改变感染后诱导的细胞信号传导和宿主反应；然而，在极少数情况下才阐明了它们精确的生化活性。利用酿酒酵母作为替代宿主，我们发现志贺氏菌效应蛋白IpaH9.8通过促进蛋白酶体依赖性对丝裂原活化蛋白激酶激酶（MAPKK）Ste7的降解来中断信息素反应信号传导。在体外，IpaH9.8对泛素和Ste7表现出泛素连接酶活性。在植物和动物病原体的IpaH同源物中不变的一个半胱氨酸残基的替换消除了IpaH9.8的泛素连接酶活性。我们还提供证据表明，来自肠炎沙门氏菌的IpaH同源物SspH1可以使泛素和PKN1（先前鉴定的SspH1相互作用伙伴）泛素化。这项研究确定了IpaH家族成员作为E3泛素连接酶的功能。
