We use a bioengineering approach to design probiotic bacteria to express and deliver antimicrobial peptides that inhibit multidrug-resistant pathogens, including Enterococcus faecium, Salmonella enterica, Clostridia perfringens and E. coli.
Figure. An engineering approach to design and test antimicrobial probiotics that clear VRE in patients GI tracts. In preliminary results, we demonstrate these systems in vitro and in vivo. The main hypothesis to test in this Phase I project: cocktails of antimicrobials delivered by modified probiotic microbes eliminate VRE inside animal GI tracts. With libraries of components, General Probiotics will establish platforms for rapid design and testing of viable antimicrobial products.
Probiotic bacteria are organisms thought to confer health benefits to their host organisms. Importantly, probiotics can be engineered as ideal therapeutic delivery vehicles: they are bile-resistant, they are generally regarded as safe to consume, and they may reside inside GI tracts for tunable time intervals.
Antimicrobial peptides (AMPs) are naturally occurring bactericidal proteins. AMPs can be engineered to target pathogens, and can be produced and delivered by probiotics.
We test the capacity of AMP-producing probiotics to reduce pathogen counts in animal models. We challenge animals with clinical isolates of pathogenic microbes and examine disease outcomes when the animals are treated with recombinant probiotics. This research will offer proof-of-concept data and validate the main hypothesis that AMP-producing probiotics can significantly reduce antibiotic-resistant bacteria in GI tracts.