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Role of the Y. pseudotuberculosis YscF protein in toxin delivery into host cells

假结核杆菌 YscF 蛋白在毒素递送至宿主细胞中的作用

基本信息

批准号：
7806882
负责人：
ALISON J DAVIS
金额：
$ 0.11万
依托单位：
TUFTS UNIVERSITY BOSTON
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-04-15 至 2012-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7806882
关键词：
Bacteria Bacterial Infections Bacterial Toxins Cell Communication Cell membrane Cells Chemicals Complex Cultured Cells Cytolysis Cytosol Defect Digestive System Disorders Disabled Persons Disease Distal Electron Microscopy Erythrocytes Escherichia coli Escherichia coli EHEC Extracellular Space Genetic Screening Goals Host Defense Human Infection Intestinal Diseases Link Maps Mass Spectrum Analysis Membrane Monitor Mutagenesis Mutation Needles Pasteurella pseudotuberculosis Principal Investigator Process Protein Analysis Protein translocation Proteins Research Role Salmonella Shigella Site Structure Suppressor Mutations Surface System Testing Toxin Travel Type III Secretion System Pathway Virulence Virulence Factors Work Yersinia Yersinia pestis V antigen antimicrobial drug appendage base crosslink enteric pathogen insight mutant pathogen prevent protein protein interaction

项目摘要

DESCRIPTION (provided by applicant): Gram-negative enteropathogenic bacteria, including Yersinia, Salmonella, Shigella and both enteropathogenic and enterohemorrhagic E. coli, cause a wide variety of gastero intestinal diseases in humans. All of these pathogens harbor an essential virulence factor called the Type III Secretion System which delivers bacterial toxins directly into host cells. The Type III Secretion System produces a structure in the bacterial membrane with a needle-like appendage extending out from the bacterial surface through which toxins are secreted. The secretion system also produces a pore in the host plasma membrane, termed the translocon, which allows access of the toxins to the host cell cytosol. It is not known how the needle on the bacterial surface and the translocon in the host cell membrane cooperate to enable toxin delivery. In an effort to determine the requirements for a productive needle-translocon interaction during infection I have isolated mutations in the needle protein of Yersinia pseudotuberculosis (YscF) that are incapable of delivering toxins into the host cell, but retain the ability to secrete toxins out of the bacteria into the extracellular space. In this proposal, I aim to use both WT Yersinia and the yscF mutants to: 1) determine if the needle is in direct contact with the translocon during infection, 2) determine if the needle-translocon interaction is required for pore formation in the host cell and 3) map the regions in YscF and the partner protein that are required for needle-translocon interactions. Characterization of the bacteria-host cell interactions using both WT and mutant Yersinia will provide insight into the mechanism of toxin delivery into host cells used by Y. pseudotuberculosis. This virulence mechanism is conserved amongst other enteric pathogens, and thus this work will be directly applicable to the study of disease caused by Salmonella, Shigella and E. coli, and will uncover candidates for targets of anti-microbial agents.

描述（由申请人提供）：