Mechanism by which glabridin combined with β-lactam antibiotics attenuates MRSA pathogenicity and drug resistance

The novelty of this study lies in the discovery that the natural product glabridin (Glb) acts as a multi-target inhibitor. It directly binds to AgrA and AgrC proteins, effectively blocks the quorum sensing system, and thereby significantly downregulates the expression of key virulence factors such as alpha-hemolysin. More importantly, Glb in combination with ampicillin or cephalexin synergistically reduces the IC50 of the antibiotics and inhibits bacterial growth by disrupting cell wall synthesis. In vivo experiments further confirmed that the combination therapy effectively reduced lung injury and inflammation in a mouse model of MRSA-induced pneumonia.