Probiotics engineered to fight against human pathogens

Synthetic biology aims to engineer genetically modified biological systems that perform novel functions that do not exist in nature, with reusable, standard interchangeable biological parts. By having this engineering framework in place, synthetic biology has the potential to make the construction of novel biological systems a predictable, reliable, systematic process. In our previous study, we engineered Escherichia coli to effectively sense the presence of Pseudomonas aeruginosa and kill the pathogen by releasing antimicrobial peptide, as a proof-of-concept of a novel microbe-based antimicrobial strategy. 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 next-generation 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 development of pathogen targeting probiotics presents the potential use of a synthetic biology-driven antimicrobial strategy that can complement current antibiotic therapies to be a cost-effective therapeutic agent that is capable of rapid self-diagnosis and treatment against an infection.