Staphylococcus aureus is a bacterial pathogen that causes food poisoning, various infections, and sepsis. Effective strategies and new drugs are needed to control S. aureus associated infections due to the emergence and rapid dissemination of antibiotic resistance. In the present study, the antibacterial activity, potential mode of action, and applications of flavonoids from licorice were investigated. Here, we showed that glabrol, licochalcone A, licochalcone C, and licochalcone E displayed high efficiency against methicillin-resistant Staphylococcus aureus (MRSA). Glabrol, licochalcone A, licochalcone C, and licochalcone E exhibited low cytotoxicity without hemolytic activity based on safety evaluation. Glabrol displayed rapid bactericidal activity with low levels of resistance development in vitro. Meanwhile, glabrol rapidly increased bacterial membrane permeability and dissipated the proton move force. Furthermore, we found that peptidoglycan, phosphatidylglycerol, and cardiolipin inhibited the antibacterial activity of glabrol. Molecular docking showed that glabrol binds to phosphatidylglycerol and cardiolipin through the formation of hydrogen bonds. Lastly, glabrol showed antibacterial activity against MRSA in both in vivo and in vitro models. Altogether, these results suggest that glabrol is a promising lead compound for the design of membrane-active antibacterial agents against MRSA and can be used as a disinfectant candidate as well.

中文翻译：

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甘草中的黄酮类化合物对耐甲氧西林金黄色葡萄球菌的抗菌作用和作用方式。

金黄色葡萄球菌是引起食物中毒，各种感染和败血症的细菌病原体。由于抗生素耐药性的出现和迅速传播，需要有效的策略和新药来控制金黄色葡萄球菌相关感染。在本研究中，对甘草中的黄酮类化合物的抗菌活性，潜在作用方式和应用进行了研究。在这里，我们显示了萘普洛尔，甘草甜菜碱A，甘草甜菜碱C和甘草甜菜碱E对耐甲氧西林的金黄色葡萄球菌（MRSA）表现出很高的效率。根据安全性评估，Glabrol，licochalcone A，licochalcone C和licochalcone E表现出低细胞毒性，而无溶血活性。Glabrol在体外显示出快速的杀菌活性，且耐药性水平较低。与此同时，萘普洛尔迅速增加了细菌膜的渗透性并消散了质子移动力。此外，我们发现肽聚糖，磷脂酰甘油和心磷脂抑制了格拉普洛尔的抗菌活性。分子对接表明，格拉普洛尔通过氢键的形成与磷脂酰甘油和心磷脂结合。最后，在体内和体外模型中，格拉普洛尔均显示出对MRSA的抗菌活性。总而言之，这些结果表明，萘普洛尔是用于设计针对MRSA的膜活性抗菌剂的有前途的先导化合物，也可以用作消毒剂。分子对接表明，格拉普洛尔通过氢键的形成与磷脂酰甘油和心磷脂结合。最后，在体内和体外模型中，格拉普洛尔均显示出对MRSA的抗菌活性。总而言之，这些结果表明，萘普洛尔是用于设计针对MRSA的膜活性抗菌剂的有前途的先导化合物，也可以用作消毒剂。分子对接表明，格拉普洛尔通过氢键的形成与磷脂酰甘油和心磷脂结合。最后，在体内和体外模型中，格拉普洛尔均显示出对MRSA的抗菌活性。总而言之，这些结果表明，萘普洛尔是用于设计针对MRSA的膜活性抗菌剂的有前途的先导化合物，也可以用作消毒剂。