Biogenesis of the Coxiella-containing vacuole

含有柯克斯体的液泡的生物发生

基本信息

批准号：
9206481
负责人：
Craig R. Roy
金额：
$ 41.7万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-02-01 至 2020-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9206481
关键词：
ACBD3 gene Acute Disease Autophagocytosis Autophagosome Bacteria Biochemical Biogenesis Biological Assay Cell physiology Cells Chronic Complement Coxiella Coxiella burnetii Cytosol Defect Disease Endocarditis Environment Event Exhibits GTP-Binding Protein alpha Subunits, Gs Gammaproteobacteria Genes Genetic Genetic Screening Genome Health Host Defense Human Immune Evasion Infection Lead Legionella Libraries Life Style Lysosomes Mammals Mediating Microbe Organelles Organism Pathogenesis Pathogenicity Pathway Analysis Pathway interactions Phenotype Phylogenetic Analysis Play Property Protein Secretion Proteins Q Fever Role Synteny System Testing Vacuole Virulence Visual Yeasts cell type combat genetic approach human disease innovation insight loss of function microbial mutant pathogen protein function public health relevance trait yeast two hybrid system

项目摘要

DESCRIPTION (provided by applicant): Coxiella burnetii is an intracellular pathogen that causes the human disease Q-fever. Mechanisms by which this bacterial pathogen exploits human cells remain unknown. This project is focused on the activities of virulence determinants in Coxiella that are essential for biogenesis of a vacuole that supports bacterial replication. One of the essential determinants for biogenesis of the Coxiella-containing vacuole (CCV) is the Dot/Icm system, which is a functional type IVb protein secretion machine that promotes infection by delivering bacterial effectors into host cells. We have identified Coxiella mutants that are deficient in effector proteins, which led to the identification of effector proteins that function n vacuole biogenesis. To understand how these effector proteins promote biogenesis of a vacuole that support Coxiella replication we will complete the following aims. Aim 1: Determine how Cig57 and Cig2 modulate host cell functions. Aim 2: Determine why host autophagy is essential for normal CCV biogenesis and fusion. Aim 3: Identify effector proteins that have important roles in relevant cell types.

描述（应用程序提供）：Coxiella burnetii是一种细胞内病原体，会导致人类疾病Q-Fever。这种细菌病原体利用人类细胞的机制仍然未知。该项目的重点是确定在考氏病毒中的活性，这对于支持细菌复制的真空醇的生物发生至关重要。一 DOT/ICM系统是含紫红菌（CCV）的生物发生的必需决定剂，它是一种功能性的IVB蛋白分泌机器，它通过将细菌效应传递到宿主细胞中来促进感染。我们已经确定了在效应蛋白中确定的coxiella突变体，这导致鉴定出效应蛋白，该效应蛋白在液泡生物发生中起作用。为了了解这些效应蛋白如何促进吸尘器的生物发生，从而支持Coxiella复制，我们将完成以下目的。 AIM 1：确定CIG57和CIG2如何调节宿主细胞功能。目标2：确定为什么宿主自噬对于正常的CCV生物发生和融合至关重要。目标3：确定在相关细胞类型中具有重要作用的效应蛋白。