Subversion of retrogade trafficking by Legionella pneumophila

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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.