Role of Yersinia Yops in an Animal Infection Model

超出提供的空间。病原菌克服宿主防御，在粘膜表面和哺乳动物组织中建立感染。因此，了解发生在这些部位的细菌与宿主的相互作用对于了解宿主的防御和免疫至关重要。致病性耶尔森氏菌、假结核耶尔森氏菌、鼠疫耶尔森氏菌和小肠结肠炎耶尔森氏菌都含有一个毒力质粒PYV，它编码III型分泌器的组成部分以及称为YOPs的效应蛋白。III型分泌系统将YOPs注入哺乳动物细胞，在那里它们扰乱和/或改变哺乳动物细胞的功能。大多数YOP在培养细胞中具有多个蛋白质靶点和生化活性。然而，他们在动物感染模型中的细胞靶点是未知的。YopH和YopE是关键的毒力因子，使耶尔森氏菌能够在许多组织中定居并导致疾病。通过研究YopH和YopE在感染动物模型系统中对特定宿主蛋白作用的缺陷突变，YopH和YopE必须灭活的蛋白质靶标将被确定，以使耶尔森菌能够在组织中定植并导致疾病。此外，在感染期间注射YopH和YopE的宿主细胞以及在不同组织中杀死yopH和yopE突变体的宿主细胞类型将被识别。这些知识结合在一起，将揭示YopH和YopE在不同组织中针对的宿主防御，以及YopH和YopE需要的特定活动，以挫败这些宿主防御，使耶尔森菌能够定植并致病。这个项目的长期目标是了解所有YOPs对耶尔西尼亚菌种的作用。在动物组织中定植并引起疾病，并了解防止、抗击和/或遏制组织中耶尔森菌感染的宿主防御系统。表演网站========================================Section End===========================================

EXCEED THE SPACE PROVIDED. 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. PERFORMANCE SITE ========================================Section End===========================================