The Combined Strategy of Baicalin and Oxacillin Sodium Against Methicillin-Resistant Staphylococcus aureus: Biofilm Inhibition, Virulence Attenuation and In Vivo Anti-Infection Efficacy

Abstract

Simple Summary Methicillin-resistant Staphylococcus aureus (MRSA) infections present significant therapeutic challenges and constitute a major public health hazard. While the synergistic application of phytochemicals alongside conventional antibiotics offers a promising strategy to suppress bacterial growth with a reduced risk of triggering resistance, the precise mechanisms underlying this antibacterial effect and its in vivo efficacy remain poorly understood. Our study demonstrates that co-administration of baicalin and oxacillin sodium facilitates the intracellular buildup of reactive oxygen species (ROS). Furthermore, this combination reduces the levels of extracellular polymeric substances (EPSs) and total protein within biofilms, suppresses the metabolic functions of biofilm cells, and hinders the production of key virulence factors, specifically lipase and staphyloxanthin. These observed anti-biofilm and anti-virulence effects are likely attributable to the downregulation of sarA gene expression induced by the baicalin-oxacillin sodium mixture. Building on these findings, we further assessed the in vivo anti-infective potential of this combined therapy. The results indicated that this combined therapy significantly decreased the infiltration of inflammatory cells within the peritoneal cavity of murine models, suppressed the production of pro-inflammatory mediators, and reduced bacterial burdens in tissues. Furthermore, it facilitated the restoration of pathological tissue injuries and exhibited protective properties for both hepatic and renal functions. In conclusion, the synergistic application of baicalin and sodium oxacillin effectively impedes MRSA biofilm development and virulence factor synthesis, thereby attenuating pathogenicity in a mouse model of peritonitis induced by MRSA USA300 strain. These findings validate the anti-infective efficacy of integrating plant-derived compounds with conventional antibiotics, offering novel experimental support for clinical strategies aimed at managing peritonitis caused by drug-resistant pathogens.