Abstract Background Enterobacter hormaechei ( E. hormaechei ) is an opportunistic pathogen in poultry, increasingly associated with multidrug resistance due to the extensive use of antibiotics in animal production. The emergence of resistant E. hormaechei strains poses a significant threat to poultry health and food safety, highlighting the urgent need for alternative antimicrobial strategies. This study aimed to isolate and characterize a novel lytic bacteriophage targeting E. hormaechei and to evaluate its biological properties and therapeutic potential in a gastrointestinal infection mice model. Results A lytic phage, designated S18-3, was isolated from environmental water using E. hormaechei strain HZW1 isolated from diseased broiler liver. Phage S18-3 forms clear plaques (~ 0.6 cm) and exhibits an icosahedral head with a long tail. Optimal infectivity occurs at an MOI of 0.1. S18-3 remains stable from 30 to 50 °C and tolerates a broad pH range (pH 4–11). Whole-genome sequencing revealed no known virulence factors or antimicrobial resistance genes, indicating favorable genetic safety. In a murine intestinal infection model established by antibiotic pretreatment and oral challenge, E. hormaechei caused significant weight loss and mortality. Oral administration of S18-3 markedly improved survival and mitigated weight loss compared with infected controls. Phage S18-3 titers were detectable in feces in infection group, with only transient, low-level presence in blood. Histopathology showed no evident liver injury or inflammatory changes, suggesting no hepatotoxicity associated with phage treatment. Conclusions Phage S18-3 is a stable, genetically safe lytic phage that effectively alleviates intestinal E. hormaechei infection in a murine model without observable adverse effects. These data support the potential of S18-3 as an antibiotic alternative for controlling E. hormaechei infections in poultry. Further validation in broiler models and farm-level settings is warranted to assess translational applicability in sustainable poultry production.
Wang et al. (Wed,) studied this question.