Microbial biosensor for sensing and treatment of intestinal inflammation

Abstract

Substantial synthetic biology efforts have been made to engineer biosensors to detect intestinal inflammation, however none target the most clinically accepted biomarker, calprotectin. To develop an in situ biosensor for calprotectin, we optimized a zinc uptake regulator (Zur) regulated promoter coupled with a memory circuit that can detect and record intestinal inflammation in vivo. The level of activation strongly correlates with calprotectin levels in the colon of two independent mouse models of colitis. Coupling of the biosensor with the production of the anti-inflammatory cytokine IL-10 allowed for the resolution of chemically induced colitis, demonstrating the ability of the biosensor to sense and respond to disease. This work highlights the utility of developing synthetic organisms for the diagnosis and treatment of intestinal disease using clinically validated biomarkers. One sentence summaryWe have optimized a microbial biosensor to detect and respond to the clinically relevant intestinal inflammation biomarker calprotectin.