(796a) Probiotics Engineered to Fight Against Human Pathogens

There is a growing sense of urgency in searching for a new effective treatment regimen for infectious diseases as the emergence of multi-drug resistant pathogens continue to pose threats. 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 engineered E. coli Nissle, a probiotic strain, to be equipped with clinically relevant functionalities to fight against P. aeruginosa infection. Nissle is a non-pathogenic and therapeutically relevant bacterium that is currently used for gastrointestinal disorder treatment. We developed novel genetic circuits that allow Nissle to move towards P. aeruginosa and produce bacteriocin and biofilm-degrading enzyme, thereby targeting two prominent states of the pathogen; planktonic and biofilm. With enhanced sensitivity and added functionalities, the killing efficiencies of the engineered Nissle were further demonstrated in Caenorhabditis elegans and mice infection models. This study extends the proof-of-concept design of engineered microbes to a novel synthetic biology-driven antimicrobial strategy, that can potentially be applied in fighting P. aeruginosa and other infectious pathogens.