Genetic Analysis of Legionella Phagosome Trafficking

军团菌吞噬体贩运的遗传分析

• 批准号: 7319175
• 负责人: Craig R. Roy
• 金额: $ 39.3万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7319175
• 关键词: Animal Model; Biogenesis; Biological; C-terminal; Cell Communication; Cells; Eukaryotic Cell; Goals; Grant; Integration Host Factors; Legionella; Legionella pneumophila; Mediating; Membrane; Membrane Protein Traffic; Molecular; Pathogenesis; Phagosomes; Process; Protein Secretion; Proteins; RabGDI; Regulation; Role; Secretory Vesicles; Specificity; Structure; System; Transmembrane Transport; Transport Vesicles; Vacuole; Work; genetic analysis; protein function; target SNARE proteins; trafficking

DESCRIPTION (provided by applicant): Legionella pneumophila is a valuable model organism for identifying bacterial determinants that modulate vesicular transport. Central to the process of L. pneumophila manipulation of host membrane trafficking is a type IV-related protein secretion system called Dot/lcm that is required for the establishment of a vacuole that supports bacterial replication in eukaryotic cells. The goal of this grant is to understand how the Dot/lcm system governs biogenesis of the specialized vacuole in which L. pneumophila replication occurs. We have identified and determined the biological activities for several L. pneumophila effector proteins translocated into host cells by the Dot/lcm system. Our goal over the next granting period will be to elucidate the molecular mechanisms that underlie the functioning of these Dot/lcm effectors to understand how they manipulate host proteins important for replication of L. pneumophila inside of eukaryotic cells. This work will provide a more detailed understanding of how Dot/lcm effector proteins modulate host cell interactions to facilitate the intracellular replication and pathogenesis of L. pneumophila.

描述（由申请人提供）：嗜肺军团菌是一种有价值的模型生物，用于鉴定调节囊泡运输的细菌决定因素。嗜肺军团菌操纵宿主膜运输过程的核心是一种称为 Dot/lcm 的 IV 型相关蛋白分泌系统，该系统是建立支持细菌在真核细胞中复制的液泡所必需的。这笔资助的目标是了解 Dot/lcm 系统如何控制嗜肺军团菌复制发生的特殊液泡的生物发生。我们已经鉴定并确定了通过 Dot/lcm 系统转入宿主细胞的几种嗜肺军团菌效应蛋白的生物活性。我们在下一个资助期间的目标将是阐明这些 Dot/lcm 效应器功能背后的分子机制，以了解它们如何操纵对真核细胞内嗜肺军团菌复制至关重要的宿主蛋白。这项工作将更详细地了解 Dot/lcm 效应蛋白如何调节宿主细胞相互作用，以促进嗜肺军团菌的细胞内复制和发病机制。