Isolation and characterization of broad-host-range bacteriophages and their alleviation of liver and kidney injury in a mouse model of S. aureus infection.

In recent years, Staphylococcus aureus has emerged as a global concern due to its contamination of food and its role in human infections, posing a significant threat to public health. In this study, 47 strains of S. aureus were isolated from 266 milk samples, with an overall positive rate of 17.67%. Variety virulence and biofilm-related genes were identified, and a total of 17 spa types and 13 sequence types were discovered, with ST97, ST188 and ST398 being the predominant ones. Notably, methicillin-resistant Staphylococcus aureus (MRSA) strains were identified. A broad-spectrum bacteriophage targeting multiple S. aureus sequence types was isolated from sewage. This phage exhibited high activity across a wide range of temperatures (20 °C - 50 °C), pH (3-11), and sodium chloride concentrations (up to 3 M). No genes associated with antibiotic resistance, virulence factors, and tRNA were found in the phage genome, and it belongs to the Kayvirus genus of the Herelleviridae family. This phage effectively inhibits S. aureus biofilms and reduces bacterial counts in food in a dose-dependent manner. Phage therapy, due to its highly specific targeting of bacteria, has been proven effective in our S. aureus-induced mouse model. In this model, the phage treatment increased food intake and body weight, reduced bacterial load in various organs, and alleviated liver and kidney damage, as well as the systemic inflammatory response caused by S. aureus. These findings provide valuable insights into the role of S. aureus in food contamination and offer preliminary theoretical basis for using bacteriophages as biological agents.