Engineered Probiotics That Detect and Kill the Human Pathogen Vibrio Cholerae

New synthetic biology techniques have enabled us to engineer the human microbiota for therapeutic purposes. In this project, we have engineered the probiotic lactic acid bacteria Lactococcus lactis to detect Vibrio cholerae, the causative agent of the infectious disease cholera. We used the CqsS sensor domain from the V. cholerae CAI-1 quorum-sensing system to create a hybrid two component system in L. lactis that can directly detect the V. cholerae CAI-1 signal. Incorporation of a TetR-based signal inverter into the detection circuit allowed us to couple CAI-1 recognition to activation of the output module, where a combination of several antimicrobial peptides will be used to specifically kill V. cholerae. We have tested the circuit in vitro and in co-culture conditions and will carry out in vivo tests in a V. cholerae mouse infection model in the near future. This novel design uses the pathogen’s own sensing system to detect and kill it.