1. A process for controlling intracellular bacterial infections induced by membrane injury.
- Author
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Roy D, Liston DR, Idone VJ, Di A, Nelson DJ, Pujol C, Bliska JB, Chakrabarti S, and Andrews NW
- Subjects
- Animals, Bacteria metabolism, Bacterial Proteins genetics, Bacterial Proteins metabolism, CHO Cells, Calcium metabolism, Cells, Cultured, Cricetinae, Endocytosis, Exocytosis, Listeria monocytogenes growth & development, Lysosomes microbiology, Lysosomes physiology, Macrophages microbiology, Membrane Glycoproteins genetics, Mice, Mutation, Nerve Tissue Proteins genetics, Permeability, Phagosomes microbiology, Phagosomes physiology, Salmonella typhimurium metabolism, Synaptotagmins, Vacuoles microbiology, Yersinia pseudotuberculosis genetics, Yersinia pseudotuberculosis growth & development, Bacteria growth & development, Calcium-Binding Proteins, Cell Membrane physiology, Membrane Glycoproteins physiology, Nerve Tissue Proteins physiology, Salmonella typhimurium growth & development
- 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.
- Published
- 2004
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