Role of Yersinia Yops in an Animal Infection Model

描述（由申请方提供）：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至关重要。致病性耶尔森氏菌（Yersinia spps）、Y. pseudotuberculosis，Y.鼠疫菌和Y.所有小肠结肠炎菌都含有毒力质粒pYV，其编码III型分泌装置的组分以及称为Yops的效应蛋白。III型分泌系统将Yops注射到哺乳动物细胞中，在那里它们破坏和/或改变哺乳动物细胞功能。大多数Yop在培养的细胞中具有多种蛋白质靶标和生化活性。然而，它们在动物感染模型中的细胞靶点是未知的。YopH和YopE是重要的毒力因子，使耶尔森氏菌能够在许多组织中定植并引起疾病。通过研究YopH和YopE的突变体，这些突变体在感染的动物模型系统中对特定宿主蛋白的作用是有缺陷的，YopH和YopE必须定位的蛋白质靶点将被确定，以使耶尔森氏菌能够定殖组织并引起疾病。此外，将鉴定在感染期间注射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。结合起来，这些知识将揭示YopH和YopE在不同组织中靶向的宿主防御，以及YopH和YopE阻止这些宿主防御所需的特定活性，以使耶尔森氏菌能够定植并引起疾病。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，并了解预防、对抗和/或控制组织中耶尔森氏菌感染的宿主防御。

DESCRIPTION (provided by applicant): 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.