Engineered gut bacteria deploy in situ phage therapy to ward off Salmonella infection in mice

A non-pathogenic E. coli was engineered to stably carry a P22 prophage that is modified to produce obligately lytic P22* phages, enabling the gut to host high levels of anti-Salmonella phage before infection. Prophylactic colonization with these lyto-lysogens reduced Salmonella Typhimurium burden and improved survival in mouse models, outperforming administration of free phage or post-infection treatment. The study demonstrates a proof-of-concept for prophylactic prophage therapy, using engineered bacteria as living phage factories to protect against enteric pathogens.