Functional Probiotics Engineered to Eradicate P. Aeruginosa

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 a human pathogen, Pseudomonas aeruginosa, as a proof-of-concept of a novel microbe-based antimicrobial strategy using the priciples of synthetic biology. In this study, we have chosen a probiotic strain, to develop into therapeutic microbes with clinically relevant functionalities to fight against human pathogen. The implemented functionalities include the ability of the probiotic microbes to swim toward P. aeruginosa upon sensing and disrupt biofilm, and exert strong antimicrobial activity against gastrointestinal infections. The latest engineered cells were able to demonstrate pathogen specific cell migration that can sense and kill the pathogen. Furthermore, this target localization was observed in the presence of mature biofilm, which is responsible for antibiotic-resistance and chronic infection, thereby exhibiting significantly improved killing efficiency compared to its non-motile counterpart. The effective antimicrobial activities against target human pathogens have also been shown in eukaryotic infection models. This study suggests the possibility that probiotics could potentially be engineered for prevention and treatment of infectious diseases, which may provide an antimicrobial strategy that is complementary to current antibiotic therapies.