Characterization of virulence factors in shigellosis

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.

Grant Number: 5R21AI178051-02
NIH Institute/Center: NIH
Principal Investigator: HERVE AGAISSE