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Mutant of Salmonella typhimurium lacking the inhibitory function for phagosome-lysosome fusion in murine macrophages
Y Ishibashi1, K Nobuta, T Arai
1Department of Microbiology, Meiji College of Pharmacy, Tokyo, Japan.
Abstract:
It has recently been described that Salmonella typhimurium is capable of inhibiting phagosome-lysosome fusion in murine macrophages after ingestion. We selected a mutant of S. typhimurium lacking the phagosome-lysosome fusion inhibitory function from a collection of Tn5-insertion mutants and examined its relevance to the pathogenesis in mice. The Tn5 insertion mutant which has a defect in fusion inhibitory function was found to be significantly sensitive to the intracellular killing by murine macrophages in vitro. However, the loss of the fusion inhibitory function did not reduce the level of virulence for mice in vivo. These results demonstrated that fusion inhibition did not play a critical role in the pathogenesis of S. typhimurium although it might contribute to at least a part of the resistance against macrophage killing mechanisms.
Insights
Salmonella typhimurium uses a specific function to inhibit phagosome-lysosome fusion in macrophages. However, disabling this Salmonella virulence factor did not affect disease severity in mice.
Area of Science:
- Microbiology
- Immunology
- Bacterial Pathogenesis
Background:
- Salmonella typhimurium is known to evade host immune responses.
- Phagosome-lysosome fusion is a critical mechanism for macrophage-mediated killing of ingested bacteria.
- Previous studies suggest Salmonella typhimurium can inhibit this fusion process.
Purpose of the Study:
- To investigate the role of Salmonella typhimurium's phagosome-lysosome fusion inhibitory function in bacterial pathogenesis.
- To determine if inhibiting this function impacts bacterial survival within macrophages and virulence in a mouse model.
Main Methods:
- Generation and selection of a Salmonella typhimurium Tn5-insertion mutant with impaired fusion inhibitory function.
- In vitro assessment of the mutant's sensitivity to intracellular killing by murine macrophages.
- In vivo evaluation of the mutant's virulence in a mouse model.
Main Results:
- The Salmonella typhimurium mutant lacking fusion inhibitory function was significantly more susceptible to killing by murine macrophages in vitro.
- Despite increased susceptibility to macrophage killing in vitro, the loss of fusion inhibitory function did not attenuate Salmonella typhimurium virulence in vivo.
- These findings indicate that fusion inhibition contributes to resistance against macrophage killing but is not essential for Salmonella typhimurium pathogenesis.
Conclusions:
- Phagosome-lysosome fusion inhibition is not a critical determinant of Salmonella typhimurium virulence in mice.
- This mechanism may play a partial role in Salmonella typhimurium's survival against macrophage-mediated defenses.
- Further research is needed to fully elucidate the contribution of this evasion strategy to overall bacterial pathogenesis.