Role of Yersinia Yops in an Animal Infection Model

病原菌克服宿主防御以在粘膜表面和哺乳动物中建立感染 组织中因此，了解在这些位点发生的细菌-宿主相互作用对于了解 宿主防御和免疫力致病性耶尔森氏菌（Yersinia spps）、Y. pseudotuberculosis，Y.鼠疫菌和Y. 小肠结肠炎菌都含有编码III型分泌物组分的毒力质粒pYV 装置以及效应蛋白，称为Yops。III型分泌系统将Yops注入 哺乳动物细胞，其中它们破坏和/或改变哺乳动物细胞功能。大多数Yop人都有多种蛋白质 培养细胞中的靶点和生化活性。然而，它们在动物感染中的细胞目标 模型未知。YopH和YopE是重要的毒力因子，使耶尔森氏菌能够在许多 组织并导致疾病。通过研究YopH和YopE的突变体， 在感染的动物模型系统中的宿主蛋白质，该蛋白质靶向YopH和YopE必须被抑制。 使耶尔森氏菌能够在组织中定植并引起疾病的定义。此外，宿主细胞是 在感染过程中注射YopH和YopE的细胞和在感染中杀死yopH和yopE突变体的宿主细胞类型。 将识别不同的组织。结合起来，这些知识将揭示YopH针对的主机防御 和YopE在不同组织中的活性以及YopH和YopE的特异性活性需要阻止这些宿主 使耶尔森氏菌能够定居并引起疾病。该项目的长期目标是 了解所有Yops对耶尔森氏菌的作用。在动物组织中定殖并引起疾病， 了解宿主防御，防止，战斗和/或包含组织中的耶尔森氏菌感染。

Pathogenic bacteria overcome host defenses to establish infections at mucosal surfaces and in mammalian tissues. Thus, understanding bacterial-host interactions that occur at these sites is critical to understanding host defenses and immunity. Pathogenic Yersinia spps, Y. pseudotuberculosis, Y. pestis and Y. enterocolitica all contain a virulence plasmid, pYV, that encodes components of a type III secretion apparatus as well as effector proteins, called Yops. The type III secretion system injects Yops into mammalian cells where they disrupt and/or alter mammalian cell function. Most Yops have multiple protein targets and biochemical activities in cultured cells. However, their cellular targets in an animal infection model are unknown. YopH and YopE are crucial virulence factors that allow Yersinia to colonize many tissues and cause disease. By studying mutants of YopH and YopE that are defective in acting on specific host proteins in an animal model system of infection, the protein targets that YopH and YopE must inactivate to enable Yersinia to colonize tissues and cause disease will be defined. In addition, the host cells that are injected with YopH and YopE during infection and the host cell types that kill yopH and yopE mutants in different tissues will be identified. Combined, this knowledge will reveal the host defenses targeted by YopH and YopE in different tissues and the specific activities of YopH and YopE needed to thwart these host defenses to enable Yersinia to colonize and cause disease. The long-term goals of this project are to understand the role of all Yops for Yersinia spp. to colonize and cause disease in animal tissues and to understand the host defenses that prevent, combat and/or contain Yersinia infection in tissues.