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Published on: August 19, 2020
Critical role of bacterial dissemination in an infant rabbit model of bacillary dysentery
Lauren K Yum1, Mariana X Byndloss2, Sanford H Feldman3
1Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA, USA.
Abstract:
The bacterial pathogen Shigella flexneri causes 270 million cases of bacillary dysentery (blood in stool) worldwide every year, resulting in more than 200,000 deaths. A major challenge in combating bacillary dysentery is the lack of a small-animal model that recapitulates the symptoms observed in infected individuals, including bloody diarrhea. Here, we show that similar to humans, infant rabbits infected with S. flexneri experience severe inflammation, massive ulceration of the colonic mucosa, and bloody diarrhea. T3SS-dependent invasion of epithelial cells is necessary and sufficient for mediating immune cell infiltration and vascular lesions. However, massive ulceration of the colonic mucosa, bloody diarrhea, and dramatic weight loss are strictly contingent on the ability of the bacteria to spread from cell to cell. The infant rabbit model features bacterial dissemination as a critical determinant of S. flexneri pathogenesis and provides a unique small-animal model for research and development of therapeutic interventions.
Insights
A new infant rabbit model effectively mimics Shigella flexneri infection, showing severe inflammation and bloody diarrhea. This model is crucial for developing new treatments for bacillary dysentery.
Area of Science:
- Microbiology
- Pathogenesis
- Animal Models
Background:
- Shigella flexneri causes millions of bacillary dysentery cases and deaths globally.
- Existing small-animal models fail to replicate key human symptoms like bloody diarrhea.
Purpose of the Study:
- To establish and validate a novel small-animal model for Shigella flexneri infection.
- To investigate the pathogenic mechanisms of S. flexneri in a human-relevant model.
Main Methods:
- Infection of infant rabbits with S. flexneri.
- Histopathological analysis of colonic tissue.
- Assessment of bacterial dissemination and host immune response.
Main Results:
- Infant rabbits infected with S. flexneri developed severe inflammation, colonic ulceration, and bloody diarrhea.
- Type III secretion system (T3SS)-dependent invasion is essential for initial inflammation and vascular damage.
- Bacterial cell-to-cell spread is critical for severe ulceration, bloody diarrhea, and weight loss.
Conclusions:
- The infant rabbit model accurately recapitulates human Shigella flexneri infection symptoms.
- Bacterial dissemination is a key factor in S. flexneri pathogenesis.
- This model offers a valuable platform for therapeutic development against bacillary dysentery.
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