Characterization of virulence factors in shigellosis

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Abstract The intestinal pathogen Shigella flexneri is the causative agent of bacillary dysentery (bloody diarrhea) 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 has been the lack of a small-animal model that recapitulates the symptoms observed in infected individuals. Our group has recently developed a unique model of bacillary dysentery in infant rabbits. In this model, animals infected with S. flexneri experience massive epithelial cell fenestration, vascular lesions, immune cell infiltration, and bloody diarrhea. While the bacterial factors supporting S. flexneri intracellular infection have been chiefly determined using tissue culture systems, we know very little about the virulence determinants leading to pathogenesis in infected individuals. In this application, we propose to use the infant rabbit model in conjunction with Transposon-sequencing approaches to identify and characterize the bacterial factors supporting bacillary dysentery.