title: Pathogen trafficking pathways and host phosphoinositide metabolism.
abstract: Phosphoinositide (PI) glycerolipids are key regulators of eukaryotic signal transduction, cytoskeleton architecture and membrane dynamics. The host cell PI metabolism is targeted by intracellular bacterial pathogens, which evolved intricate strategies to modulate uptake processes and vesicle trafficking pathways. Upon entering eukaryotic host cells, pathogenic bacteria replicate in distinct vacuoles or in the host cytoplasm. Vacuolar pathogens manipulate PI levels to mimic or modify membranes of subcellular compartments and thereby establish their replicative niche. Legionella pneumophila, Brucella abortus, Mycobacterium tuberculosis and Salmonella enterica translocate effector proteins into the host cell, some of which anchor to the vacuolar membrane via PIs or enzymatically turnover PIs. Cytoplasmic pathogens target PI metabolism at the plasma membrane, thus modulating their uptake and antiapoptotic signalling pathways. Employing this strategy, Shigella flexneri directly injects a PI-modifying effector protein, while Listeria monocytogenes exploits PI metabolism indirectly by binding to transmembrane receptors. Thus, regardless of the intracellular lifestyle of the pathogen, PI metabolism is critically involved in the interactions with host cells.
authors.affiliation: Institute of Microbiology, ETH Zürich, Wolfgang-Pauli-Strasse 10, 8093 Zürich, Switzerland.
authors.forename: Stefan S
authors.initials: SS
authors.lastname: Weber
authors.forename: Curdin
authors.initials: C
authors.lastname: Ragaz
authors.forename: Hubert
authors.initials: H
authors.lastname: Hilbi
mesh_terms: D001419:Bacteria / Q000378:metabolism / Q000472:pathogenicity*; D010588:Phagosomes / Q000382:microbiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D015398:Signal Transduction; D014617:Vacuoles / Q000382:microbiology*
chemical_list: D010716:Phosphatidylinositols; D019869:Phosphatidylinositol 3-Kinases; D010744:Phosphoric Monoester Hydrolases