A Novel Lytic Salmonella Phage Harboring an Unprecedented Tail-Protein Domain Combination Capable of Lysing Cross-Host-Transmitted Salmonella Strains

The emergence of multidrug-resistant Salmonella poses a significant threat to global public health and food safety, necessitating the urgent search for new strategies to replace conventional antibiotics. Phages are viruses that can directly target bacteria and have garnered attention in recent years for their development as antibiotic alternatives. In this study, 4458 samples were collected from farms, supermarkets, and human feces, yielding 65 strains of Salmonella, which were serotyped using multiplex PCR. Subsequently, a lytic phage was isolated and identified using the dominant serotype of Salmonella as the host bacterium. We further explored the biological characteristics of this phage through host range, growth properties, and genomic analysis. Finally, we analyzed the potential of the phage to block the cross-host transmission of Salmonella, combining PFGE Salmonella classification, strain sources, and phage lytic phenotypes. The results showed that phage gmqsjt-1 could lyse 69. 23% (45/65) of Salmonella, of which 75. 56% (34/45) were resistant strains. The optimal multiplicity of infection (MOI) for gmqsjt-1 was 0. 01, with a latent period of about 10 min, maintaining high activity within the temperature range of 30 to 60 °C and pH range of 2 to 13. No virulence or resistance genes were detected in the gmqsjt-1 genome, which carries two tail spike proteins (contain FAD binding₂ superfamily, the Tail spike TSP1/Gp66 N-terminal domain, and the Pectin lyase fold) and a holin–lysozyme–spanin lytic system. Phylogenetic classification indicates that phage gmqsjt-1 belongs to a new genus and species of an unnamed family within the class Caudoviricetes. PFGE classification results show a high genetic relationship among human, farm animal, and food source Salmonella, and the comprehensive lytic phenotype reveals that phage gmqsjt-1 can lyse Salmonella with high genetic correlation. These results suggest that this novel lytic Salmonella phage has the potential to inhibit cross-host transmission of Salmonella, making it a promising candidate for developing alternative agents to control Salmonella contamination sources (farms), thereby reducing the risk of human infection with Salmonella through ensuring food system safety.