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Pathogenesis of experimental salmonellosis: inhibition of protein synthesis by cytotoxin
Abstract:
Salmonella cytotoxin present in cell lysates inhibited protein synthesis in both Vero cells and isolated rabbit intestinal epithelial cells. A time-course experiment with Vero cells revealed progressive inhibition of protein synthesis beginning as early as 1 h after exposure to the Salmonella cell lysate. Significant loss of membrane integrity of Vero cells (measured by release of [3H]uridine) did not appear before 24 h. To demonstrate inhibited protein synthesis in intestinal tissue during experimental salmonellosis, we isolated rabbit epithelial cells from Salmonella-infected and control intestinal loops. Measurement of [3H]leucine incorporation showed a similar decrease in protein synthesis in epithelial cells from the Salmonella-infected intestinal loop as that from an adjacent control loop. A similar pattern of protein synthesis inhibition was observed when isolated epithelial cells from normal rabbit intestine were exposed to the Salmonella cell lysate. The inhibited protein synthesis in the intestinal cells provides a molecular basis for the cellular damage caused by Salmonella cytotoxin during experimental salmonellosis.
Insights
Salmonella cytotoxin significantly inhibits protein synthesis in intestinal cells. This molecular mechanism explains cellular damage during salmonellosis, impacting both host and bacterial cells.
Area of Science:
- Microbiology
- Cell Biology
- Toxicology
Background:
- Salmonella infections cause significant gastrointestinal illness.
- The precise molecular mechanisms of Salmonella-induced cellular damage are not fully understood.
- Salmonella cytotoxin's role in disrupting host cell function requires further investigation.
Purpose of the Study:
- To investigate the effect of Salmonella cytotoxin on protein synthesis in intestinal epithelial cells.
- To determine the timeline of protein synthesis inhibition by Salmonella cytotoxin.
- To establish a molecular basis for cellular damage during experimental salmonellosis.
Main Methods:
- Exposure of Vero cells and isolated rabbit intestinal epithelial cells to Salmonella cell lysate.
- Time-course experiments measuring protein synthesis inhibition via [3H]leucine incorporation.
- Assessment of cell membrane integrity using [3H]uridine release.
Main Results:
- Salmonella cytotoxin progressively inhibited protein synthesis in Vero cells within 1 hour.
- Significant loss of membrane integrity in Vero cells was observed only after 24 hours.
- Protein synthesis was similarly inhibited in epithelial cells from Salmonella-infected rabbit intestinal loops and in normal cells exposed to the cytotoxin.
Conclusions:
- Salmonella cytotoxin directly inhibits protein synthesis in intestinal epithelial cells.
- Inhibition of protein synthesis precedes significant loss of cell membrane integrity.
- This disruption of protein synthesis provides a molecular explanation for cellular damage in salmonellosis.