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生物利用度增强的Resveramax™调节群体感应并抑制铜绿假单胞菌PAO1中的生物膜形成。

Bioavailability-enhanced Resveramax™ modulates quorum sensing and inhibits biofilm formation in Pseudomonas aeruginosa PAO1.

作者信息

Vasavi H S, Sudeep H V, Lingaraju H B, Shyam Prasad K

机构信息

Bio-Medicinal Research Laboratory, Vidya Herbs Pvt. Ltd., Bangalore, Karnataka, India.

Bio-Medicinal Research Laboratory, Vidya Herbs Pvt. Ltd., Bangalore, Karnataka, India.

出版信息

Microb Pathog. 2017 Mar;104:64-71. doi: 10.1016/j.micpath.2017.01.015. Epub 2017 Jan 5.

Abstract

Quorum sensing (QS), a cell-to-cell communication mechanism present in many bacterial species plays a key role in regulating the virulence factor and biofilm formation in many pathogens, which causes severe public health risk. Therefore, interfering with QS mechanism offers an attractive strategy to combat bacterial infections. In the present study, anti-QS activity of a novel resveratrol formulation, Resveramax™, was detected using Chromobacterium violaceum biosensor bioassay and the effect of Resveramax on QS-regulated phenotypes in Pseudomonas aeruginosa PAO1 was assessed by standard protocols. Molecular docking analysis of resveratrol, the major active constituent of Resveramax, with LasR receptor protein was performed to evidence the QS-inhibitory potential of Resveramax. Results showed that Resveramax specifically inhibited the QS-mediated violacein pigment production in C. violaceum; pyocyanin production, proteolytic activity, swarming motility and biofilm formation in P. aeruginosa PAO1 in a concentration-dependent manner. Biofilms treated with Resveramax showed increased susceptibility to antibiotics when compared with the antibiotic treatment alone. Molecular docking analysis proved that resveratrol binds more rigidly with LasR receptor protein with docking score of -8.55 kJ/mol. These findings suggest that Resveramax could be used as novel QS-based antibacterial/anti-biofilm agent for the management of bacterial infections.

摘要

群体感应(QS)是许多细菌物种中存在的一种细胞间通讯机制,在调节许多病原体的毒力因子和生物膜形成方面起着关键作用,这会导致严重的公共卫生风险。因此,干扰群体感应机制为对抗细菌感染提供了一种有吸引力的策略。在本研究中,使用紫色色杆菌生物传感器生物测定法检测了一种新型白藜芦醇制剂Resveramax™的抗群体感应活性,并通过标准方案评估了Resveramax对铜绿假单胞菌PAO1中群体感应调节表型的影响。对Resveramax的主要活性成分白藜芦醇与LasR受体蛋白进行了分子对接分析,以证明Resveramax的群体感应抑制潜力。结果表明,Resveramax特异性抑制紫色色杆菌中群体感应介导的紫菌素色素产生;以浓度依赖的方式抑制铜绿假单胞菌PAO1中的绿脓菌素产生、蛋白水解活性、群集运动和生物膜形成。与单独使用抗生素治疗相比,用Resveramax处理的生物膜对抗生素的敏感性增加。分子对接分析证明,白藜芦醇与LasR受体蛋白结合更紧密,对接分数为-8.55 kJ/mol。这些发现表明,Resveramax可作为一种新型的基于群体感应的抗菌/抗生物膜剂用于管理细菌感染。

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