A process for controlling intracellular bacterial infections induced by membrane injury.
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.
Roy
Deepannita
D
Section of Microbial Pathogenesis and Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510, USA.
Liston
David R
DR
Idone
Vincent J
VJ
Di
Anke
A
Nelson
Deborah J
DJ
Pujol
Céline
C
Bliska
James B
JB
Chakrabarti
Sabyasachi
S
Andrews
Norma W
NW
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
D001426:Bacterial Proteins; D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D050857:Synaptotagmins; D002118:Calcium