Ascorbate deficiency increases progression of shigellosis in guinea pigs and mice infection models

Area of Science:

• Microbiology
• Immunology
• Nutritional Science

Background:

• Shigella species cause bacterial dysentery and shigellosis, primarily affecting children in developing nations.
• Existing animal models fail to fully replicate shigellosis symptoms, hindering research on infection and vaccine development.
• Mammals susceptible to Shigella, like humans and guinea pigs, cannot synthesize vitamin C (ascorbate).

Purpose of the Study:

• To investigate if moderate ascorbate deficiency impacts the progression and severity of shigellosis.
• To establish and utilize improved rodent models for studying Shigella infection dynamics.

Main Methods:

• Optimized a low-ascorbate diet in guinea pigs to induce moderate vitamin C deficiency without causing scurvy.
• Infected guinea pigs and Gulo-/- mice with various Shigella strains (S. sonnei, S. flexneri 5a, and 2a).
• Assessed shigellosis symptom severity, neutrophil influx, bacterial dissemination, and epithelial penetration.

Main Results:

• Moderate ascorbate deficiency significantly increased shigellosis symptom severity and duration (up to 48 hours) in guinea pigs.
• Increased neutrophil infiltration into the colonic mucosa and lumen was observed in ascorbate-deficient guinea pigs.
• Shigella demonstrated deeper organ penetration into the submucosal layer and bloodstream, and increased epithelial penetration in Gulo-/- mice.

Conclusions:

• Moderate ascorbate deficiency exacerbates shigellosis, highlighting the role of vitamin C status in infection outcome.
• The developed guinea pig and Gulo-/- mouse models offer valuable tools for studying Shigella pathogenesis and host-pathogen interactions.
• These models facilitate further research into Shigella infection strategies and host immune responses, potentially aiding vaccine development.