Extracellular life style of an intracellular pathogen

We will test the hypothesis that before reaching the colon where it is an intracellular pathogen, S. flexneri develops an extracellular life style relying on biofilm formation in the small intestine.

Shigella flexneri is the causative agent of bacillary dysentery (aka bloody diarrhea). The disease is caused by the replication of the bacteria in epithelial cells and systematic spread from cell to cell in the human colon, leading to complete destruction of the colonic mucosa and massive inflammation. Before reaching the colonic site of infection, S. flexneri is exposed to adverse environmental conditions, including bile salts in the small intestine. How S. flexneri adapt/resist these environmental challenges is unknown. Here we will test the hypothesis that in response to the bile salts encountered in the small intestine, S. flexneri forms a robust biolfilm that rely on the secretion of autotransporter family members. The successful completion of the project will require expertise in S. flexneri genetics (Agaisse lab), live imaging of biofilm formation (Gahlmann Lab) and  unprecedented fluorescent labelling of autotransporter family members (Ai Lab) allowing for live imaging of their secretion upon biofilm secretion.    

Desired outcomes

The successful completion of the project will require expertise in S. flexneri genetics (Agaisse lab), live imaging of biofilm formation (Gahlmann Lab) and  unprecedented fluorescent labelling of autotransporter family members (Ai Lab) allowing for live imaging of secretion . The team will engineer novel S. flexneri strains  for monitoring autotransporter secretion by live light sheet microscopy during biofilm formation. This system will allow us to test the robustness of biofilm formation as a function of the environmental conditions encountered by the bacteria as they transit through the intestinal tract, including the small intestine and the colon.