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Inhibition of macrophage phagosome-lysosome fusion by Salmonella typhimurium
1Department of Molecular Biology, Research Institute of Scripps Clinic, La Jolla 92037.
Abstract:
Salmonella typhimurium-infected macrophages were examined by electron microscopy to determine whether intracellular survival of S. typhimurium is associated with failure of bacteria containing phagosomes to fuse with secondary lysosomes. S. typhimurium 14028 actively inhibited phagosome-lysosome fusion and appeared to preferentially divide within unfused phagocytic vesicles. In comparison with Escherichia coli, S. typhimurium inhibited phagosome-lysosome fusion in peritoneal macrophages, J774 macrophages, and bone marrow-derived macrophages from both BALB/c (itys) and SWR/J (ityr) mice. The mechanism responsible for Salmonella inhibition of phagosome-lysosome fusion is unknown but requires viable salmonellae, is not blocked by opsonization with fresh normal mouse serum, and is not due to lipopolysaccharide. Inhibition of phagosome-lysosome fusion may play a critical role in survival of salmonellae within macrophages and in virulence.
Insights
Salmonella typhimurium actively prevents phagosome-lysosome fusion in macrophages, allowing the bacteria to survive and multiply within these immune cells. This inhibition is crucial for Salmonella survival and virulence.
Area of Science:
- Microbiology
- Immunology
- Cell Biology
Background:
- Macrophages are key immune cells that engulf and destroy pathogens like Salmonella typhimurium.
- Phagosome-lysosome fusion is a critical cellular process for eliminating internalized bacteria.
Purpose of the Study:
- To investigate if Salmonella typhimurium's intracellular survival is linked to its ability to block phagosome-lysosome fusion.
- To compare the phagosome-lysosome fusion inhibition by Salmonella typhimurium with that of Escherichia coli.
Main Methods:
- Electron microscopy was used to examine Salmonella typhimurium-infected macrophages.
- Experiments were conducted on various macrophage types, including peritoneal, J774, and bone marrow-derived macrophages from different mouse strains.
Main Results:
- Salmonella typhimurium actively inhibited phagosome-lysosome fusion in all tested macrophage types.
- The bacteria preferentially divided within unfused phagocytic vesicles.
- Inhibition required viable Salmonella and was not affected by opsonization or lipopolysaccharide.
Conclusions:
- Salmonella typhimurium's ability to inhibit phagosome-lysosome fusion is a significant factor in its intracellular survival within macrophages.
- This mechanism likely plays a critical role in Salmonella virulence and pathogenesis.