title: The phosphoinositide phosphatase SopB manipulates membrane surface charge and trafficking of the Salmonella-containing vacuole.
abstract: Shifts in electrostatic surface charge of membranes have recently been highlighted as a significant factor contributing to protein targeting to the plasma membrane and nascent phagosomes. Intracellular, vacuole-adapted pathogens may also regulate surface charge of their vacuoles to establish a replicative niche. Since Salmonella enterica serovar Typhimurium controls trafficking of the Salmonella-containing vacuole (SCV) and inhibits its fusion with lysosomes, we investigated the contribution of surface charge to this process. Using recently developed fluorescent biosensors, we show that the bacterial phosphoinositide phosphatase SopB controls membrane surface charge of nascent SCVs by reducing levels of negatively charged lipids phosphatidylinositol-4,5-bisphosphate and phosphatidylserine. This SopB activity results in dissociation of a number of host-cell endocytic trafficking proteins from this compartment and inhibits SCV-lysosome fusion. Moreover, inducible reduction of negative charge rescues DeltasopB bacteria-containing SCVs from fusion with lysosomes. These results reveal a membrane-charge-based mechanism used by S. Typhimurium to control SCV maturation.
authors.affiliation: Cell Biology Program, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
authors.forename: Malina A
authors.initials: MA
authors.lastname: Bakowski
authors.forename: Virginie
authors.initials: V
authors.lastname: Braun
authors.forename: Grace Y
authors.initials: GY
authors.lastname: Lam
authors.forename: Tony
authors.initials: T
authors.lastname: Yeung
authors.forename: Won Do
authors.initials: WD
authors.lastname: Heo
authors.forename: Tobias
authors.initials: T
authors.lastname: Meyer
authors.forename: B Brett
authors.initials: BB
authors.lastname: Finlay
authors.forename: Sergio
authors.initials: S
authors.lastname: Grinstein
authors.forename: John H
authors.initials: JH
authors.lastname: Brumell
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D004560:Electricity; D054884:Host-Pathogen Interactions; D006801:Humans; D007425:Intracellular Membranes / Q000737:chemistry* / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000032:analysis; D010718:Phosphatidylserines / Q000032:analysis; D012486:Salmonella typhimurium / Q000472:pathogenicity*; D014617:Vacuoles / Q000737:chemistry / Q000382:microbiology*; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D008565:Membrane Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D010718:Phosphatidylserines; D037521:Virulence Factors; C489224:SopB protein, Salmonella