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.

本研究的创新之处在于发现天然产物光甘草定（glabridin，Glb）可作为多靶点抑制剂。其可直接结合AgrA与AgrC蛋白，有效阻断群体感应（quorum sensing）系统，进而显著下调α-溶血素（alpha-hemolysin）等关键毒力因子的表达。更为关键的是，Glb与氨苄青霉素（ampicillin）或头孢氨苄（cephalexin）联合使用时，可协同降低抗生素的半最大效应浓度（IC50），并通过破坏细胞壁合成抑制细菌生长。体内实验进一步证实，该联合疗法在耐甲氧西林金黄色葡萄球菌（MRSA）诱导的小鼠肺炎模型中，可有效减轻肺损伤与炎症反应。