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Macrophage killing is an essential virulence mechanism of Salmonella typhimurium
S W Lindgren1, I Stojiljkovic, F Heffron
1Department of Microbiology and Immunology, Oregon Health Sciences University, Portland 97201, USA.
Abstract:
Phagocytic cells are a critical line of defense against infection. The ability of a pathogen to survive and even replicate within phagocytic cells is a potent method of evading the defense mechanisms of the host. A number of pathogens survive within macrophages after phagocytosis and this contributes to their virulence. Salmonella is one of these pathogens. Here we report that 6-14 hr after Salmonella enters the macrophage and replicates, it resides in large vacuoles and causes the destruction of these cells. Furthermore, we identified four independently isolated MudJ-lacZ insertion mutants that no longer cause the formation of these vacuoles or kill the macrophages. All four insertions were located in the ompR/envZ regulon. These findings suggest that killing and escape from macrophages may be as important steps in Salmonella pathogenesis as are survival and replication in these host cells.
Insights
Salmonella typhimurium evades host defenses by replicating within macrophages, causing cell destruction. Mutants unable to form these vacuoles or kill macrophages were identified, suggesting cell killing is crucial for Salmonella pathogenesis.
Area of Science:
- Microbiology
- Immunology
- Cell Biology
Background:
- Phagocytic cells, like macrophages, are crucial for host defense against pathogens.
- Pathogen survival and replication within phagocytes is a key virulence mechanism.
- Salmonella typhimurium is known to survive and replicate within macrophages.
Purpose of the Study:
- To investigate the mechanisms by which Salmonella typhimurium causes macrophage destruction.
- To identify bacterial factors involved in Salmonella-induced vacuole formation and host cell lysis.
Main Methods:
- Salmonella typhimurium infection of macrophages.
- Identification and characterization of MudJ-lacZ insertion mutants.
- Analysis of vacuole formation and macrophage cytotoxicity.
Main Results:
- Salmonella typhimurium replicates within macrophages, forming large vacuoles and causing cell lysis 6-14 hours post-infection.
- Four independent MudJ-lacZ insertion mutants were identified that did not induce vacuole formation or macrophage killing.
- All identified mutations were localized within the ompR/envZ regulon.
Conclusions:
- Salmonella typhimurium actively induces vacuole formation and macrophage destruction as part of its pathogenesis.
- The ompR/envZ regulon plays a critical role in Salmonella-induced macrophage lysis.
- Killing and escape from macrophages may be as significant as survival and replication for Salmonella virulence.