The Mechanism of Emodin Against Methicillin-Resistant Staphylococcus aureus Infection and Research on Synergistic Antibiotics

Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant clinical challenge due to its multidrug resistance, particularly to β-lactam antibiotics. This study comprehensively evaluated the natural compound emodin for its anti-MRSA activity, mechanisms of action, and potential for synergy with β-lactam antibiotics. Our findings demonstrate that emodin dose-dependently inhibits MRSA growth and abrogates biofilm formation at 2× MIC. Mechanistic studies revealed that emodin compromises cell membrane and wall integrity, induces oxidative stress, and downregulates the virulence factors SPA and EsxA. Furthermore, emodin acted synergistically with β-lactam antibiotics: it enhanced the ability of cefalexin to block bacterial adhesion and invasion of HaCat cells, and potentiated the efficacy of amoxicillin in clearing MRSA from infected macrophages. In conclusion, emodin employs a multi-target mechanism against MRSA and can resensitize the bacterium to conventional β-lactam antibiotics, presenting a promising strategy for combination therapy that may help curb antibiotic use and resistance development.