A membrane-targeting magnolol derivative for the treatment of methicillin-resistant Staphylococcus aureus infections

Multidrug-resistant bacterial infections are a major global health challenge, especially the emergence and rapid spread of methicillin-resistant (MRSA) urgently require alternative treatment options. Our study has identified that a magnolol derivative as a promising agent with significant antibacterial activity against and clinical MRSA isolates (MIC = 2-8 μg/mL), showing high membrane selectivity. Unlike traditional antibiotics, demonstrated rapid bactericidal efficiency and a lower propensity for inducing bacterial resistance. Compound also could inhibit biofilm formation and eradicate bacteria within biofilms. Mechanistic studies further revealed that could target bacterial cell membranes, disrupting the integrity of the cell membrane and leading to increased DNA leakage, resulting in potent antibacterial effects. Meanwhile, also showed good plasma stability and excellent biosafety. Notably, displayed good antibacterial activity in a mouse skin abscess model of MRSA-16 infection, which was comparable to the positive control vancomycin. These findings indicated that the magnolol derivative possessed the potential to be a novel anti-MRSA infection agent.