Synthetic Microbes Engineered to Fight Human Pathogens

Given the stalled development of new antibiotics and the increasing emergence of multi-drug resistant pathogens, there is an urgent need for designing a new treatment regimen for infectious diseases. In our previous study, we engineered Escherichia coli to effectively sense and kill Pseudomonas aeruginosa, as a proof of concept of a novel microbe-based antimicrobial strategy. In this study, we have further designed and constructed additional genetic circuits that equip E. coli with other clinically relevant functionalities. In particular, we have shown that the implementation of genetic circuits that enable E. coli to move towards P. aeruginosa and produce biofilm-degrading enzymes in response to P. aeruginosa biofilm with a precise time-delay element improved killing efficiency. We have also demonstrated these killing efficiencies in animal models. This study suggests that synthetic microbes may provide a novel synthetic biology-driven antimicrobial strategy that could potentially be applied to fighting P. aeruginosa and other infectious pathogens.