Modulation of phosphoinositide metabolism by pathogenic bacteria.
Phosphoinositide metabolism plays a pivotal role in the regulation of receptor-mediated signal transduction, actin remodelling and membrane dynamics. Phosphoinositides co-ordinate these processes by recruiting protein effectors to distinct cellular membranes in a time- and organelle-dependent manner. Intracellular bacterial pathogens interfere with phosphoinositide metabolism to direct their entry into eukaryotic cells, form replication-permissive vacuoles, modulate apoptosis, or trigger fluid secretion. Gram-negative pathogens such as Legionella pneumophila, Shigella flexneri, or Salmonella enterica employ secretion systems to invade host cells by 'pathogen-triggered phagocytosis' and thereby bypass a requirement for phosphatidylinositol 3-kinases [PI(3)Ks]. Contrarily, 'receptor-mediated phagocytosis' of Yersinia spp., Listeria monocytogenes and other pathogenic bacteria depends on PI(3)Ks. Secreted effector proteins have been found to directly bind to and modify host cell phosphoinositides, thus modulating phagocytosis and intracellular survival of the pathogens. These effectors include L. pneumophila proteins that specifically attach to phosphatidylinositol 4-phosphate [PI(4)P] on the Legionella-containing vacuole, and phosphoinositide phosphatases produced by S. flexneri, S. enterica or Mycobacterium tuberculosis. This review covers current knowledge about subversion of host cell phosphoinositide metabolism by intracellular bacterial pathogens with an emphasis on recently identified secreted effector proteins directly engaging phosphoinositides.
Hilbi
Hubert
H
Institute of Microbiology, ETH Zürich, Wolfgang-Pauli Strasse 10, 8093 Zürich, Switzerland. hilbi@micro.biol.ethz.ch
D000818:Animals; D001419:Bacteria / Q000254:growth & development / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D015394:Molecular Structure; D018129:Phosphatidylinositol Phosphates / Q000737:chemistry / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism
D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; C037178:phosphatidylinositol 4-phosphate; D010744:Phosphoric Monoester Hydrolases; C061816:phosphatidylinositol-3-phosphatase