Regulation of Yersenia pestis virulence genes in response to host cell contact

鼠疫耶尔森氏菌毒力基因响应宿主细胞接触的调节

• 批准号: 7739891
• 负责人: DEBORAH M ANDERSON
• 金额: $ 18.38万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-19 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7739891
• 关键词: Affect; Bacteria; Bioinformatics; Biological Assay; Calcium; Cell membrane; Cells; Complex; Cytoplasm; Data; Development; Disease; Dose; Event; Genes; Goals; Immune; In Vitro; Infection; Injection of therapeutic agent; Investigation; Laboratories; Lead; Maps; Measures; Modeling; Molecular; Molecular Chaperones; Molecular Conformation; Pathogenesis; Performance; Plague; Point Mutation; Principal Investigator; Process; Proteins; Regulation; Regulatory Element; Repression; Role; Signal Transduction; System; Time; Transcriptional Activation; Type III Secretion System Pathway; Up-Regulation; Virulence; Virulence Factors; Work; Yersinia pestis; immune phagocytosis; in vivo; insight; interest; macrophage; novel; novel strategies; pathogen; prevent; programs; public health relevance; research study; response

DESCRIPTION (provided by applicant): Yersinia pestis translocate virulence factors from the bacterial cytoplasm into host immune cells during infections through the Type III Secretion System (TTSS). This system allows for rapid activation of injection of Yops, proteins that go on to disable phagocytosis and immune recognition thereby enabling bacterial replication and disease. The TTSS is a tightly coordinated process of expression, assembly of secretion and translocation pores, and injection of effector proteins that responds rapidly to inducing signs indicating contact with a host cell. Accurate timing of these events is critical to optimum performance, allowing Yersinia pestis to establish lethal infections from very small challenge doses. My laboratory is interested in the process of translocation of effector proteins, specifically in how the translocon is inserted in the plasma membrane and how this signals activation of the TTSS. In this work, we seek to gain insight into the activation of the TTSS, by establishing a basic understanding of the molecular mechanism of repression of TTSS genes in the absence of host cell contact and through the identification of genes that are directly regulated through this mechanism. Results of the proposed investigations will provide preliminary data on which we can build a program that investigates molecular events of activation of the TTSS in vivo as well as in vitro, studies which may provide insight into the molecular mechanisms of Yersinia pestis pathogenesis. PUBLIC HEALTH RELEVANCE: This proposal investigates the mechanism of regulation of the type III secretion system in Yersinia pestis, the causative agent of plague. The goal is to establish the molecular mechanism of activation of the TTSS in response to contact with host immune cells in order to study the role of this process in the development of plague.

描述（由申请人提供）：通过III型分泌系统（TTSS）在感染期间，细菌细胞质从细菌细胞质（TTSS）感染期间，耶尔森氏菌流动性毒力因子转移到宿主免疫细胞中。该系统允许快速激活注射YOPS，继续禁用吞噬作用的蛋白质和免疫识别，从而实现细菌复制和疾病。 TTSS是一个紧密协调的表达过程，分泌和易位孔的组装以及注射效应蛋白的注射，该蛋白迅速响应，以诱导指示与宿主细胞接触的迹象。这些事件的准确时机对于最佳性能至关重要，从而使耶尔西尼亚·佩斯蒂斯（Yersinia Pestis）可以通过很小的挑战剂量建立致命感染。我的实验室对效应蛋白的易位过程感兴趣，特别是对如何插入质膜中的转运量以及这种信号如何激活TTSS。在这项工作中，我们试图通过在没有宿主细胞接触的情况下以及通过这种机制直接调节的基因来建立对TTSS基因抑制的分子机制的基本理解，以深入了解TTSS的激活。拟议的研究结果将提供初步数据，我们可以在该数据上构建一个程序，该程序研究了体内TTSS激活的分子事件以及体外的研究，该研究可能会洞悉Pestis pestis发病机理的分子机制。公共卫生相关性：该提案调查了鼠疫的病原体耶尔森尼亚耶尔森尼亚耶尔森尼亚分泌系统调节的机制。目的是建立TTS激活的分子机制，以响应与宿主免疫细胞接触，以研究该过程在瘟疫发展中的作用。