Intracellular Growth of Legionella Pneumophila

嗜肺军团菌的细胞内生长

• 批准号: 6437823
• 负责人: Joseph P Vogel
• 金额: $ 24.26万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6437823
• 关键词: Legionella; bacteria infection mechanism; bacterial proteins; cell fusion; immunofluorescence technique; immunologic assay /test; intracellular parasitism; laboratory mouse; laboratory rabbit; legionellosis; macrophage; microorganism culture; microorganism growth; virulence

The long term objective of this proposal is to understand how a Gram negative bacterial pathogen, Legionella pneumophila, is able to survive and replicate inside normally bactericidal phagocytic cells. This grant will focus on determining how L. pneumophila alters the endocytic pathway and prevents phagosome-lysosome fusion of host cells. The specific aims are to characterize the Dot apparatus by examining the role of two critical Dot proteins, DotB and DotL, in the assembly and activity of the Dot/Icm complex and to identify the substrate(s) exported by this complex into the macrophage host cell. The health relatedness of this proposal is two fold. First, establishing the mechanism used by L, pneumophila to survive and replicate inside macrophages will provide additional insight into how it causes disease and may reveal novel targets to be used for drug therapy. Second, since specialized secretion systems are commonly used by a variety of bacterial pathogens, knowledge gained about the L. pneumophila secretion apparatus is likely to be applicable to understanding the molecular mechanisms of virulence used by other pathogens, and could serve as the basic to prevent or treat a number of different disease.

该提案的长期目标是了解革兰氏阴性细菌病原体嗜肺军团菌如何能够在正常杀菌的吞噬细胞内生存和复制。 这笔资助将重点确定嗜肺军团菌如何改变内吞途径并阻止宿主细胞的吞噬体-溶酶体融合。 具体目标是通过检查两种关键 Dot 蛋白 DotB 和 DotL 在 Dot/Icm 复合物的组装和活性中的作用来表征 Dot 装置，并鉴定由该复合物输出到巨噬细胞宿主细胞中的底物。 该提案与健康的相关性有两个方面。 首先，建立嗜肺军团菌在巨噬细胞内生存和复制的机制，将为了解其如何引起疾病提供更多见解，并可能揭示用于药物治疗的新靶点。 其次，由于各种细菌病原体通常使用专门的分泌系统，因此获得的有关嗜肺军团菌分泌装置的知识可能适用于理解其他病原体使用的毒力的分子机制，并且可以作为预防或治疗许多不同疾病的基础。