Biogenesis of the Coxiella-containing vacuole

含有柯克斯体的液泡的生物发生

• 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
• 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

 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（由申请方提供）：贝氏柯克斯体是一种引起人类Q热的细胞内病原体。这种细菌病原体利用人类细胞的机制仍然未知。该项目的重点是在柯克斯体的毒力决定因素的活动是必不可少的一个空泡，支持细菌复制的生物合成。一 Dot/Icm系统是含柯克斯体的空泡（CCV）生物发生的重要决定因素之一，其是通过将细菌效应物递送到宿主细胞中来促进感染的功能性IVb型蛋白分泌机器。我们已经确定了柯克斯体突变体是缺乏效应蛋白，这导致了识别的效应蛋白的功能n液泡生物发生。为了了解这些效应蛋白如何促进支持柯克斯体复制的液泡的生物发生，我们将完成以下目标。目的1：确定p57和p52如何调节宿主细胞功能。目的2：确定为什么宿主自噬对于正常的CCV生物发生和融合是必不可少的。目的3：鉴定在相关细胞类型中具有重要作用的效应蛋白。