The development of novel antibacterial agents from plant sources is emerging as a successful strategy to combat antibiotic resistance in pathogens. In this study, we systemically investigated the antibacterial activity and underlying mechanisms of baicalin against methicillin-resistant Staphylococcus aureus (MRSA) and Stenotrophomonas maltophilia. Our results showed that baicalin effectively restrained bacterial proliferation, compromised the integrity of cellular membranes, increased membrane permeability, and triggered oxidative stress within bacteria. Transcriptome profiling revealed that baicalin disrupted numerous biological pathways related to antibiotic resistance, biofilm formation, cellular membrane permeability, bacterial virulence, and so on. Furthermore, baicalin demonstrated a synergistic antibacterial effect when combined with ampicillin against both MRSA and S. maltophilia. In conclusion, baicalin proves to be a potent antibacterial agent with significant potential for addressing the challenge of antibiotic resistance in pathogens.
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