Sanguinarine fights antibiotic-resistant Staph skin infections in dogs

Abstract

OBJECTIVES: Staphylococcus pseudintermedius is a major pathogen of canine pyoderma, and its increasing antimicrobial resistance poses a potential threat to public health, making it crucial to explore the development of new alternative therapeutic agents. METHODS AND RESULTS: In this study, we investigated the in vitro antimicrobial activity and mechanism of inhibition of sanguinarine (SAN) against clinically resistant bacteria. In addition, a murine methicillin-resistant Staphylococcus pseudintermedius (MRSP) skin infection model was established to evaluate the therapeutic efficacy of SAN. In vitro assays revealed that the MIC and MBC of SAN against S. pseudintermedius were 39.06 μg˙mL-1 and 156.25 μg˙mL-1. SAN could delay MRSP entry into the logarithmic growth phase and disrupt the bacterial structure. Transcriptomic analysis revealed that SAN primarily impacted amino acid synthesis and metabolism. In a murine MRSP skin infection model, SAN significantly reduced bacterial load, increased serum IL-4 expression, and decreased IL-6 expression. Histopathological analysis showed reduced inflammation and improved skin structure in the SAN group, with abundant fibroblasts and macrophages. CONCLUSIONS: These results reveal that SAN can inhibit the growth of MRSP, the primary drug-resistant strain associated with canine pyoderma, and suggests SAN's potential as a therapeutic option to counteract the emergence of antimicrobial resistance.