Quercetin Influences Quorum Sensing in Food Borne Bacteria: In-Vitro and In-Silico Evidence.
Quercetin Influences Quorum Sensing in Food Borne Bacteria: In-Vitro and In-Silico Evidence.
复制标题
DOI：
10.1371/journal.pone.0134684
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Shetty PH
中科院分区：
文献类型：
--
作者：
Gopu V;Meena CK;Shetty PH
群体感应(Quorum Sensing，QS)在调节许多食源性致病菌的毒力因子方面起着至关重要的作用，这些致病菌造成了严重的公共卫生风险。因此，阻断QS信号通路可能是对抗微生物感染的一个有吸引力的策略。在本研究中，利用生物传感器菌株评价了槲皮素的QS抑制活性及其对食源性致病菌的抗生物被膜特性。此外，还利用分子对接和分子动力学模拟等电子计算机技术筛选了该化合物作为QS抑制剂的潜力。80μg/ml的槲皮素对紫罗兰素的产生、生物膜的形成、胞外多糖的产生、运动能力和藻酸盐的产生等QS依赖表型均有明显的抑制作用，且呈浓度依赖关系。常规抗生素与槲皮素的协同作用提高了所有受试病原菌的敏感性。此外，分子对接分析表明，与LasR受体蛋白的对接分数为-9.17Kcal/mol的信号化合物相比，槲皮素与LasR受体蛋白的结合更为牢固。分子动力学模拟预测，槲皮素的QS抑制活性是通过受体与槲皮素复合体的构象变化来实现的。以上结果表明，栎素可作为LasR受体途径信号传递化合物的竞争性抑制物，并可作为一种新型的QS类抗菌/抗生物被膜药物来管理食源性致病菌。
Quorum sensing (QS) plays a vital role in regulating the virulence factor of many food borne pathogens, which causes severe public health risk. Therefore, interrupting the QS signaling pathway may be an attractive strategy to combat microbial infections. In the current study QS inhibitory activity of quercetin and its anti-biofilm property was assessed against food-borne pathogens using a bio-sensor strain. In addition in-silico techniques like molecular docking and molecular dynamics simulation studies were applied to screen the quercetin’s potentiality as QS inhibitor. Quercetin (80μg/ml) showed the significant reduction in QS-dependent phenotypes like violacein production, biofilm formation, exopolysaccharide (EPS) production, motility and alginate production in a concentration-dependent manner. Synergistic activity of conventional antibiotics with quercetin enhanced the susceptibility of all tested pathogens. Furthermore, Molecular docking analysis revealed that quercetin binds more rigidly with LasR receptor protein than the signaling compound with docking score of -9.17Kcal/mol. Molecular dynamics simulation predicted that QS inhibitory activity of quercetin occurs through the conformational changes between the receptor and quercetin complex. Above findings suggest that quercetin can act as a competitive inhibitor for signaling compound towards LasR receptor pathway and can serve as a novel QS-based antibacterial/anti-biofilm drug to manage food-borne pathogens.