Characterization of an infant rabbit model of bacillary dysentery

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Abstract Dysentery affects hundreds of millions of people in the world each year and is characterized by damage to the intestinal tissue and rupture of blood vessels, so that visible quantities of blood are lost with defecation. Dysentery can result from viral, bacterial, or parasitic infections. The intestinal pathogen Shigella flexneri is the causative agent of bacillary dysentery and is responsible for more than 250 million cases of dysentery annually, 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. Our group has recently uncovered that similar to humans, infant rabbits infected with S. flexneri experienced severe immune cell infiltration, massive ulceration of the colonic mucosa, and bloody diarrhea. In this application, we propose to explore the infant rabbit model with wild type and mutant S. flexneri through (1) characterization of bacterial burden and associated histopathology (Aim1) and characterization of host gene expression profiles (Aim 2). The characterization of the infant rabbit model proposed in this application will provide critical molecular tools for understanding the mechanisms supporting bacillary dysentery in humans.