Modulation of the phagolysosome by Salmonella

沙门氏菌对吞噬溶酶体的调节

• 批准号: 7940619
• 负责人: CHRISTINA C TAM
• 金额: $ 2.79万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7940619
• 关键词: Bacteria; Calcium; Cells; Complex; Cytosol; Drosophila genus; Event; Growth; Host Defense Mechanism; Integral Membrane Protein; Invaded; Laboratories; Legionella pneumophila; Lysosomes; Mediating; Membrane Fusion; Mus; Phagolysosome; Phagosomes; Phenotype; Process; Proteins; Role; SNAP receptor; SPI1 gene; Salmonella; Salmonella enterica; System; Testing; Type III Secretion System Pathway; Vacuole; Work; Yersinia; design; genome wide association study; lysosome membrane; macrophage; mutant; pathogen; sensor; synaptotagmin; synaptotagmin VII

DESCRIPTION (provided by applicant): Shortly after invading host cells, Salmonella resides in vacuoles that fuse with lysosomes. This process is subsequently inhibited, allowing for bacterial survival and replication. Earlier work from the Andrews laboratory showed that permeabilization of the phagosome by the SPI1 type three secretion systems (TTSS) triggers fusion of lysosomes with Salmonella-containing vacuoles shortly after bacterial entry. This process is inhibited in synaptotagmin Vll-deficient macrophages, leading to more vigorous bacterial growth. Synaptotagmin VII, a calcium sensor molecule present on the membrane of lysosomes, interacts with the lysosomal SNARE molecule VAMP7 and facilitates lysosomal fusion. In this project we will test the hypothesis that Salmonella inhibits phagolysosomal fusion by translocating into the host cytosol effector molecules that inhibit the activity of Syt VII, VAMP7 and/or other host cell proteins that regulate phagosome-lysosome fusion.

描述（由申请人提供）：入侵宿主细胞后不久，沙门氏菌位于与溶酶体融合的液泡中。此过程随后被抑制，允许细菌存活和复制。 Andrews实验室的早期工作表明，SPI1三型分泌系统（TTSS）对吞噬体的通透性触发了细菌进入后不久，溶酶体与含沙门氏菌的液泡的融合。在缺乏巨噬细胞的突触毒素VLL中抑制了此过程，从而导致细菌生长更具剧烈的生长。 Synaptotagmin VII是存在于溶酶体膜上的钙传感器分子，与溶酶体SNARE分子VAMP7相互作用，并促进溶酶体融合。在该项目中，我们将测试以下假设：沙门氏菌通过转移到抑制SYT VII，VAMP7和/或其他调节吞噬体溶质体融合的宿主活性的宿主细胞质效应分子中抑制吞噬肿瘤体融合。