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Mechanisms of bacillary dysentery: lessons learnt from infant rabbits
1Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine , Charlottesville, VA, USA.
Abstract:
The bacterial pathogen Shigella flexneri causes more than 250 million cases of bacillary dysentery (blood in stool) every year across the world. This human-specific disease is characterized by profuse bloody diarrhea, dramatic ulceration of the colonic epithelium and immune cell infiltration of the colonic tissue. A major challenge in understanding the mechanisms supporting bacillary dysentery is the reliance on animal models that do not fully recapitulate the symptoms observed in humans, including bloody diarrhea. Here we outline advances provided by a recently developed infant rabbit model of bacillary dysentery. The infant rabbit model defines bacillary dysentery as a critical combination of massive vascular lesions and dramatic epithelial fenestration due to intracellular infection and cell-to-cell spread, respectively. The infant rabbit model provides an unprecedented framework for understanding how the cell biology of Shigella flexneri infection relates to pathogenesis.
Insights
A new infant rabbit model accurately mimics human bacillary dysentery, caused by *Shigella flexneri*. This model reveals key vascular and epithelial changes, advancing understanding of this severe diarrheal disease.
Area of Science:
- Microbiology
- Pathogenesis
- Infectious Diseases
Background:
- *Shigella flexneri* causes over 250 million annual cases of bacillary dysentery globally.
- Bacillary dysentery is characterized by bloody diarrhea, colonic ulceration, and inflammation.
- Existing animal models fail to fully replicate human symptoms like bloody diarrhea.
Purpose of the Study:
- To introduce and validate a novel infant rabbit model for studying *Shigella flexneri* pathogenesis.
- To define the key pathological features of bacillary dysentery in this new model.
- To provide a better system for investigating the cell biology of *Shigella flexneri* infection.
Main Methods:
- Development of an infant rabbit model of bacillary dysentery.
- Characterization of colonic epithelium and vascular lesions.
- Analysis of intracellular infection and cell-to-cell spread mechanisms.
Main Results:
- The infant rabbit model exhibits massive vascular lesions and epithelial fenestration.
- These findings are linked to intracellular infection and cell-to-cell spread of *Shigella flexneri*.
- The model recapitulates critical aspects of human bacillary dysentery.
Conclusions:
- The infant rabbit model offers a significant advancement for studying *Shigella flexneri* pathogenesis.
- It provides a framework to link bacterial cell biology to disease mechanisms.
- This model facilitates research into treatments and prevention strategies for bacillary dysentery.
