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Inappropriate use of antibiotics has accelerated to the emergence of multidrug-resistant bacteria, becoming a major health threat. Moreover, bacterial biofilms contribute to antibiotic resistance and prolonged infections. Bacteriophage (phage) therapy may provide an alternative strategy for controlling multidrug-resistant bacterial infections. In this study, a broad-host-range phage, SHWT1, with lytic activity against multidrug-resistant  Salmonella  was isolated, characterized and evaluated for the therapeutic efficacy  in vitro  and  in vivo . Phage SHWT1 exhibited specific lytic activity against the prevalent  Salmonella  serovars, such as  Salmonella  Pullorum,  Salmonella  Gallinarum,  Salmonella  Enteritidis, and  Salmonella  Typhimurium. Morphological analysis showed that phage SHWT1 was a member of the family  Siphoviridae  and the order  Caudovirales . Phage SHWT1 had a latent period of 5 min and burst size of ~150 plaque-forming units (PFUs)/cell. The phage was stable from pH 3-12 and 4–65°C. Phage SHWT1 also showed capacity to lyse  Salmonella  planktonic cells and inhibit the biofilm formation at optimal multiplicity of infection (MOI) of 0.001, 0.01, 0.1, and 100, respectively. In addition, phage SHWT1 was able to lyse intracellular  Salmonella  within macrophages. Genome sequencing and phylogenetic analyses revealed that SHWT1 was a lytic phage without toxin genes, virulence genes, antibiotic resistance genes, or significant genomic rearrangements. We found that phage SHWT1 could successfully protect mice against  S .  enteritidis  and  S .  typhimurium  infection. Elucidation of the characteristics and genome sequence of phage SHWT1 demonstrates that this phage is a potential therapeutic agent against the salmonellosis caused by multidrug-resistant  Salmonella .

frontiers in veterinary science

Characterization of a Broad-Host-Range Lytic Phage SHWT1 Against Multidrug-Resistant Salmonella and Evaluation of Its Therapeutic Efficacy in vitro and in vivo