William Marsh Rice University Houston United States
The overall goal of this work is to engineer synthetic probiotics orally-administered gut bacteria that sense and compute the metabolic signature of a specific disease in the colon, and respond by secreting a therapeutic compound that treats the molecular basis of the disease. Here, we combined computation and experiments to discover the first known biological sensor of thiosulfate, a two-component system from S. halifaxensis. We transferred this sensor into the gut-adapted strain E. coli Nissle 1917 and used it to control GFP expression. We then administered this sensor strain to healthy mice and mice with colitis, and demonstrated that our sensor bacteria reliably report colitis. This work is a major advance toward our vision.