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Myrtus communis and its bioactive phytoconstituent, linalool, interferes with Quorum sensing regulated virulence functions and biofilm of uropathogenic bacteria: In vitro and in silico insights
Journal of King Saud University-Science ( IF 3.8 ) Pub Date : 2021-08-28 , DOI: 10.1016/j.jksus.2021.101588
Abdullah A. Alyousef 1 , Fohad Mabood Husain 2 , Mohammed Arshad 1 , Syed Rizwan Ahamad 3 , Mohammad Shavez Khan 4 , Faizan Abul Qais 4 , Altaf Khan 5 , Abdulaziz Alqasim 1 , Naif Almutairi 1 , Iqbal Ahmad 4 , Thamer Albalawi 6 , Pravej Alam 6 , Sadique Khan 7
Affiliation  

Ever increasing spread of drug resistance among bacterial pathogens have rendered the current antibiotic therapy ineffective. Drug-resistant urinary tract infections caused by Gram negative bacterial pathogens such as Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, and Serratia marcescens are considered more severe and life threatening because of strong biofilm dependent growth characteristics among majority of them. Moreover, most uropathogens coordinate their complex virulence responses via a highly structured network of cell to cell communication known as Quorum sensing (QS). Phytochemicals/bioactive extracts obtained from established ethnomedicinal plants have previously been demonstrated as effective anti-QS agent against numerous pathogenic bacteria including uropathogens. Myrtus communis (L.) (Myrtaceae) is one such plant of immense ethnomedicinal importance and has been used in traditional medicine. In the present investigation, methanolic extract of Myrtus communis (MCME) demonstrated 65% inhibition in the QS regulated violacein production in C. violaceum without affecting the growth of the bacteria. Further, the MCME interfered significantly with QS controlled virulence production in P. aeruginosa (elastase, protease, pyocyanin and chitinase) and S. marcescens (prodigiosin and protease). The leaf extract exhibited 16–74%, 31–84%, 12–66% and 19–71% inhibition of biofilm biomass of P. aeruginosa, E. coli, A. baumannii and S. marcescens respectively at the increasing concentration corresponding to MIC/16-MIC/2. GC–MS analysis revealed Linalool as one of the major bioactive compounds present in the MCME. Further, in vitro assays demonstrated QS and biofilm inhibition by sub-MICs of linalool. In silico docking and simulation studies showed that the possible mechanisms responsible for the interference of QS were AHL synthesis inhibition, antagonization of QS-regulatory proteins, and blocking of the receptor proteins. Thus, from the obtained results it is envisaged that M. communis and its bioactive compound linalool may have medicinal implications and could prove as effective therapeutic agent in combating the threat of biofilm based persistent infections caused by uropathogenic bacteria.



中文翻译:

桃金娘及其生物活性植物成分芳樟醇干扰群体感应调节的毒力功能和尿路致病菌的生物膜:体外和计算机洞察

耐药性在细菌病原体中的不断扩散已经使当前的抗生素治疗无效。引起的革兰氏阴性细菌病原体如耐药性尿路感染铜绿假单胞菌,大肠杆菌,鲍曼不动杆菌,粘质沙雷氏菌由于其中大多数具有强烈的生物膜依赖性生长特征,因此被认为更严重并危及生命。此外,大多数尿路病原体通过称为群体感应 (QS) 的高度结构化的细胞间通讯网络来协调其复杂的毒力反应。从已建立的民族药用植物中获得的植物化学物质/生物活性提取物先前已被证明是针对多种病原菌(包括尿路病原体)的有效抗 QS 剂。香桃木(L.)(桃金娘科)是巨大的ethnomedicinal重要的一个这样的工厂,并在传统医药已被使用。在本研究中,桃金娘(MCME) 的甲醇提取物对QS 调控的紫罗兰素生产有 65% 的抑制作用。C. violaceum不影响细菌的生长。此外,MCME 显着干扰铜绿假单胞菌(弹性蛋白酶、蛋白酶、绿脓素和几丁质酶)和粘质链球菌(灵菌红素和蛋白酶)中QS 控制的毒力产生。叶提取物表现出 16-74%、31-84%、12-66% 和 19-71% 的对铜绿假单胞菌大肠杆菌鲍曼不动杆菌粘质沙门生物膜生物量的抑制作用,浓度增加对应于MIC/16-MIC/2。GC-MS 分析显示芳樟醇是 MCME 中存在的主要生物活性化合物之一。此外,体外分析证明了芳樟醇的亚 MIC 对 QS 和生物膜的抑制作用。计算机对接和模拟研究表明,干扰 QS 的可能机制是 AHL 合成抑制、QS 调节蛋白的拮抗和受体蛋白的阻断。因此,从获得的结果可以设想,M.communis及其生物活性化合物芳樟醇可能具有医学意义,并且可以证明是有效的治疗剂,可以对抗由尿路致病菌引起的基于生物膜的持续感染的威胁。

更新日期:2021-09-12
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