In this study, with canine pyoderma-affected dogs as the objects of investigation and research, relatively systematic epidemiological data were formed, and 28 strains of Staphylococcus Pseudointermedius were isolated, all of which demonstrated multi-drug resistance. With multi-drug-resistant Staphylococcus Pseudointermedius as the host bacteria, three broad-spectrum and highly efficient phages were screened out, all presenting the characteristics of virulent phages. They could enhance the sensitivity of multi-drug-resistant Staphylococcus Pseudointermedius to antibiotics, reduce the usage of antibiotics, and thereby decrease the pressure on bacteria to develop drug resistance. Through gene and protein sequencing, the phages were analyzed, and the related genes and proteins played significant roles in the lysis of Staphylococcus Pseudointermedius by the phages. The combined application of phages and antibiotics for the treatment of animal disease models was carried out. The recovery deg

Methicillin-resistant Staphylococcus pseudintermedius (MRSP) presents a significant challenge to animal health due to its multidrug resistance. Additionally, cross-infections between animals, and between animals and humans, pose potential risks to public health security. Greater attention is warranted to address the drug resistance exhibited by animal-derived bacteria. Phages—viruses naturally prevalent in the environment and the human body that specifically infect bacteria—offer an innovative approach to combating drug-resistant bacterial infections. In this study, dogs diagnosed with pyoderma were selected as the research subjects, resulting in the development of a comprehensive epidemiological dataset. A total of 82 bacterial strains, representing 29 species across 15 genera, were isolated. Among these, 28 strains of Staphylococcus pseudintermedius exhibited multidrug resistance. Using these multidrug-resistant Staphylococcus pseudintermedius strains as host bacteria, three broad-spectrum and highly efficient virulent phages were identified. These phages demonstrated the ability to enhance the susceptibility of multidrug-resistant Staphylococcus pseudintermedius to antibiotics. Furthermore, genomic and proteomic analyses of the phages revealed key genes and proteins responsible for the effective lysis of Staphylococcus pseudintermedius. The combined application of phages and antibiotics was evaluated in animal disease models, with therapeutic efficacy assessed using measures such as visual appearance scoring, histopathological analysis, and tissue bacterial load quantification. Results showed that the group treated with a combination of phages and antibiotics exhibited the most significant recovery from superficial pyoderma, followed by the group treated with phages alone. In contrast, no notable difference was observed between the control group and the antibiotic-only group, both of which yielded the poorest therapeutic outcomes. This study provides a promising new therapeutic strategy for the clinical management of canine pyoderma in veterinary practice while also contributing valuable insights for enhancing public health security.