Engineered E. coli that detect and respond to gut inflammation through nitric oxide sensing.

Advances in synthetic biology now allow for the reprogramming of microorganisms to execute specific tasks. Here, we describe the development of an engineered strain of E. coli capable of sensing and responding to the presence of a mammalian inflammatory signal. The synthetic gene regulatory circuit is designed to permanently alter gene expression in response to the well characterized inflammatory signal nitric oxide. The detection of nitric oxide initiates the expression of a DNA recombinase, causing the permanent activation of a DNA switch. We demonstrate that E. coli containing this synthetic circuit respond to nitric oxide from both chemical and biological sources, with permanent DNA recombination occurring in the presence of nitric oxide donor compounds or inflamed mouse ileum explants. In the future, this synthetic genetic circuit will be optimized to allow E. coli to reliably detect and respond to inflammation in vivo.