A first-of-its-kind preventive phage therapy has shown promising results in protecting mice from Salmonella infection. The research, led by Associate Professor Bryan Hsu and his team, involved engineering a non-harmful strain of E. coli to carry a specific type of virus called a phage. This phage is designed to target and kill Salmonella bacteria. The method aims to protect the gut from infection by creating a high concentration of phages before Salmonella enters the digestive system. The study was published in the journal Nature Microbiology. The team used a technique involving a "lytic phage-producing lysogen," also known as a "lyto-lysogen." This is a combination of a phage and a bacterial host. In this case, the E. coli bacteria was modified to carry a phage that only infects Salmonella. Once introduced into the gut, the phage recognizes and attacks Salmonella, killing it through a process called lysis, where the bacterial cell bursts open. To help the phage better target Salmonella, the researchers inserted a Salmonella gene into the E. coli genome, tricking the bacteria into accepting the phage as non-threatening. This allowed the phage to effectively infect, multiply, and destroy Salmonella. Phage therapy has been challenging for treating intestinal infections because phages and bacteria often coexist in the gut for long periods. This makes it difficult to achieve the high ratio of phages to bacteria needed for an effective treatment. Additionally, once an infection is established, the bacteria can hide within the gut lining, making them hard for phages to reach and destroy. The researchers chose to target Salmonella because it causes significant illness worldwide and is increasingly resistant to antibiotics. It is also considered a high-priority pathogen by the Centers for Disease Control and Prevention. The study's findings could have broader implications for treating other bacterial infections, as the method used could be adapted to target different pathogens. Rogerio A. Bataglioli, the study's lead author and a postdoctoral fellow, plans to continue his research on bacteriophages at the School of Chemical Engineering at the State University of Campinas in São Paulo, Brazil.