Sapindus saponins are natural nonionic surfactants, and they have a broad-spectrum antibacterial effect, but few studies have elucidated the antibacterial mechanism of Sapindus saponins to date. Therefore, this study screened the antibacterial activity of Sapindus saponins singly and in combination against 7 bacteria, and investigated the synergistic antibacterial action via targeting cell membrane proteins. The only combination of Sapindoside A and B (S_AB) with synergistic activity against Micrococcusluteus (M. luteus) was obtained, where the MICs of Sapindoside A and B were one fourth of their individual minimum inhibitory concentration (MIC). After treatment with S_AB, the spectral features of protein in the cell membrane of M. luteus showed obvious changes based on Raman spectroscopy, and the constitutions of membrane proteins were changed seriously. Besides, changes in protein microenvironment was observed, and the contribution of Sapindoside A was greater than that of Sapindoside B with concentration below 2MIC. Molecular docking also demonstrated that Sapindoside A interacted with penicillin-binding protein 2, and showed higher binding energy than Sapindoside B, further indicating that the greater contribution in the synergistic action of S_AB on membrane proteins. Collectively, these results showed that the synergistic antibacterial action of Sapindoside A and B against M. luteus could be achieved by attacking cell membrane proteins, and Sapindoside A played a major role, suggesting that S_AB has the potential to be the natural antibacterial detergent additive in food industry, although it is limited in its scope of antimicrobial activity against foodborne bacteria.

无患子皂苷是天然的非离子表面活性剂，具有广谱抗菌作用，但迄今为止对无患子皂苷的抗菌机制的研究很少。因此，本研究筛选了无患子皂苷单独和联合对7种细菌的抗菌活性，并通过靶向细胞膜蛋白研究了协同抗菌作用。获得了无患子苷 A 和 B (S _AB ) 对微球菌( M. luteus ) 具有协同活性的唯一组合，其中无患子苷 A 和 B 的 MIC 是它们各自最低抑菌浓度 (MIC) 的四分之一。S _AB处理后, 细胞膜中蛋白质的光谱特征M. luteus 的拉曼光谱显示出明显的变化，膜蛋白的组成发生了严重的变化。此外，观察到蛋白质微环境的变化，当浓度低于2MIC时，无患子苷A的贡献大于无患子苷B。分子对接还表明无患子苷A与青霉素结合蛋白2相互作用，并显示出比无患子苷B更高的结合能，进一步表明无患子苷_A对膜蛋白的协同作用贡献更大。总的来说，这些结果表明无患子苷 A 和 B 对M. luteus的协同抗菌作用可以通过攻击细胞膜蛋白来实现，而无患子苷 A 发挥了主要作用，这表明 S _AB具有成为食品工业中天然抗菌洗涤剂添加剂的潜力，尽管它对食源性细菌的抗菌活性范围有限。