title: A process for controlling intracellular bacterial infections induced by membrane injury.
abstract: Strategies for inhibiting phagolysosome fusion are essential for the intracellular survival and replication of many pathogens. We found that the lysosomal synaptotagmin Syt VII is required for a mechanism that promotes phagolysosomal fusion and limits the intracellular growth of pathogenic bacteria. Syt VII was required for a form of Ca2+-dependent phagolysosome fusion that is analogous to Ca2+-regulated exocytosis of lysosomes, which can be triggered by membrane injury. Bacterial type III secretion systems, which permeabilize membranes and cause Ca2+ influx in mammalian cells, promote lysosomal exocytosis and inhibit intracellular survival in Syt VII +/+ but not -/- cells. Thus, the lysosomal repair response can also protect cells against pathogens that trigger membrane permeabilization.
authors.affiliation: Section of Microbial Pathogenesis and Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Deepannita
authors.initials: D
authors.lastname: Roy
authors.forename: David R
authors.initials: DR
authors.lastname: Liston
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Idone
authors.forename: Anke
authors.initials: A
authors.lastname: Di
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Nelson
authors.forename: Céline
authors.initials: C
authors.lastname: Pujol
authors.forename: James B
authors.initials: JB
authors.lastname: Bliska
authors.forename: Sabyasachi
authors.initials: S
authors.lastname: Chakrabarti
authors.forename: Norma W
authors.initials: NW
authors.lastname: Andrews
mesh_terms: D000818:Animals; D001419:Bacteria / Q000254:growth & development* / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins; D002462:Cell Membrane / Q000502:physiology*; D002478:Cells, Cultured; D006224:Cricetinae; D004705:Endocytosis; D005089:Exocytosis; D008089:Listeria monocytogenes / Q000254:growth & development; D008247:Lysosomes / Q000382:microbiology / Q000502:physiology; D008264:Macrophages / Q000382:microbiology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D010539:Permeability; D010588:Phagosomes / Q000382:microbiology / Q000502:physiology; D012486:Salmonella typhimurium / Q000254:growth & development* / Q000378:metabolism; D050857:Synaptotagmins; D014617:Vacuoles / Q000382:microbiology; D015011:Yersinia pseudotuberculosis / Q000235:genetics / Q000254:growth & development
chemical_list: D001426:Bacterial Proteins; D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D050857:Synaptotagmins; D002118:Calcium