Role of Yersinia Yops in an Animal Infection Model

病原菌克服宿主防御，在粘膜表面和哺乳动物体内建立感染 纸巾。因此，了解在这些部位发生的细菌-宿主相互作用对于理解 宿主防御和豁免权。致病性耶尔森氏菌、假结核耶尔森氏菌、鼠疫耶尔森氏菌和耶尔森氏菌。 小肠结肠炎病毒都含有一种毒力质粒PYV，它编码III型分泌物的成分。 以及称为YOPs的效应器蛋白。III型分泌系统将YOPs注射到 干扰和/或改变哺乳动物细胞功能的哺乳动物细胞。大多数YOP含有多种蛋白质 培养细胞的靶标和生化活性。然而，他们在动物感染中的细胞靶点 型号不详。YopH和YopE是关键的毒力因子，允许耶尔西氏菌在许多 组织，并导致疾病。通过研究YopH和YopE在特定作用上存在缺陷的突变体 宿主蛋白在感染的动物模型系统中，YopH和YopE必须灭活的蛋白靶标 为了使耶尔森氏菌能够在组织中定居并引起疾病，将对其进行定义。此外，宿主细胞是 感染过程中注射YopH和YopE以及宿主细胞类型对yopH和yopE突变体的杀伤作用 不同的组织将被识别出来。综合起来，这些知识将揭示YopH针对的宿主防御 和YopE在不同组织中的表达以及阻断这些宿主所需的YopH和YopE的特异性 使耶尔西氏菌能够定居和致病的防御系统。这个项目的长期目标是 了解所有YOP对耶尔森氏菌的作用。在动物组织中定居并引起疾病，以及 了解防止、对抗和/或遏制组织中耶尔森氏菌感染的宿主防御系统。

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.