Subversion of retrogade trafficking by Legionella pneumophila

环境细菌通过吸入或摄入传播给人类，并可能通过在宿主细胞内生长而导致疾病。嗜肺军团菌在自由生活的环境中阿米巴和肺的免疫细胞中复制，从而导致一种被称为军团病的严重肺炎。嗜肺性乳杆菌生长在宿主细胞内的一个膜结合的隔间，即“军团细胞内的空泡”。这种特殊的液泡与宿主细胞的内体和分泌囊泡运输途径相联系，但不与杀菌溶酶体融合。军团菌空泡的形成是一个复杂而稳健的过程，涉及细菌蛋白分泌系统和150多种不同分泌的“效应蛋白”。这些蛋白质被注入宿主细胞，在那里它们调节细胞的生物和生化过程，有利于细菌。一些效应蛋白可以颠覆真核细胞信号通路和膜动力学的关键调节因子，例如磷脂酰肌醇或小的GTP酶。本项目的目的是分析嗜肺乳杆菌的细胞内复制和军团菌空泡的形成，重点是(I)新的细菌逆转录相互作用蛋白RipA和宿主反转录复合体，(Ii)细菌磷酸肌醇磷酸酶LppA和LCV磷酸肌醇模式。

Environmental bacteria are transmitted to humans by inhalation or ingestion and may cause diseases by growing within host cells. Legionella pneumophila replicates in free-living environmental amoeba and in immune cells of the lung, thereby causing a severe pneumonia termed “Legionnaires’ disease”. L. pneumophila grows within host cells in a membrane-bound compartment, the “Legionellacontaining vacuole”. This specific vacuole communicates with the endosomal and secretory vesicle trafficking pathways of the host cell, but does not fuse with bactericidal lysosomes. The formation of Legionella vacuoles is a complex and robust process, which involves a bacterial protein secretion system and more than 150 different secreted “effector proteins”. These proteins are injected into host cells, where they modulate cell biological and biochemical processes in favor of the bacteria. Some effector proteins subvert pivotal regulators of eukaryotic signaling pathways and membrane dynamics, e.g., phosphoinositide lipids or small GTPase enzymes. The aims of this project are to analyze intracellular replication of L. pneumophila and formation of Legionella vacuoles by focusing on (i) the novel bacterial retromer-interacting protein RipA and the host retromer complex, and (ii) the bacterial phosphoinositide phosphatase LppA and the LCV phosphoinositide pattern.