Chinese medicinal herb extract inhibits PQS-mediated quorum sensing system in Pseudomonas aeruginosa

Chinese medicinal herb extract inhibits PQS-mediated quorum sensing system in Pseudomonas aeruginosa
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中药提取物抑制铜绿假单胞菌中 PQS 介导的群体感应系统。

DOI:
10.1016/j.jep.2019.112272
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发表时间:
2020
影响因子:
5.4
通讯作者:
Li Yan
Li Yan
中科院分区:
医学2区
文献类型:
--
作者:
Wei Qing;Bhasme Pramod;Wang Zhiguo;Wang Li;Wang Shiwei;Zeng Yunfei;Wang Yi;Ma Luyan Z.;Li Yan

文献摘要

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民族药理学相关性中草药长期以来被认为是对抗疾病的重要资源,是数千年来医疗保健系统的重要组成部分。(艾叶、白藓根皮和茄子根)对人类机会致病菌铜绿假单胞菌的作用。材料和方法我们结合表型测定、转录分析和化学研究来确定MHE抑制的潜在机制。制备标准样品,构建群体感应系统的转录报告基因。电泳迁移率变动分析被用来澄清的机制。GC-MS和分子对接被用来确定MHE和潜在的binding agents.ResultsWe发现,MHE与细菌细胞的共培养没有改变的生长速度,但大大削弱了生产的毒力因子,如吩嗪绿脓菌素,铁载体绿脓菌和生物膜的形成。三个主要的群体感应(QS)系统的转录响应。MHE结果显示,假单胞菌喹诺酮信号(PQS)系统被完全抑制,rhlR/rhlIQS系统被中度抑制,而lasR/lasIQS系统仅受到轻微影响,提示MHE可能选择性靶向PQS系统抑制细菌毒力。电泳迁移率变动分析(EMSA)显示MHE抑制MvfR与相应的pqsA启动子区域的结合,表明MHE作为竞争剂猝灭了P中的QS功能。结论MHE是一种有效的抗细菌感染的药物。
Ethnopharmacological relevanceChinese medicinal herbs have long been recognized as important resources that can be used for the struggle against diseases and a significant component of health care system for thousands of years.Aim of the studyIn order to understand their roles in the treatment against bacterial infections, we examined the underlying mechanisms of one of the medicinal herb extracts (MHE) (Artemisiae argyiFolium, the root bark ofCortexdictamniand the root ofSolanum melongena) on the human opportunistic pathogen Pseudomonas aeruginosa.Materials and methodsWe combined phenotypic assays, transcriptional analysis and chemical investigations to identify the mechanisms underlying MHE inhibition. The standard sample was prepared and transcriptional reporters for quorum sensing systems were constructed. Electrophoretic mobility shift assays were used to clarify the mechanism. GC-MS and molecular docking were used to identify the chemicals in MHE and potential binding agents.ResultsWe found that co-culturing of MHE with bacterial cells did not change the growth rate but substantially attenuate the production of virulence factors such as phenazine pyocyanin, siderophore pyoverdine and biofilm formation. Transcriptional responses of three major quorum sensing (QS) systems ofP. aeruginosato MHE showed thatPseudomonasquinolone signaling (PQS) system was completely repressed,rhlR/rhlIQS system was moderately inhibited, whilelasR/lasIQS system was only slightly affected, suggesting that MHE might selectively target the PQS system to inhibit bacterial virulence. Furthermore, electrophoretic mobility shift assays (EMSA) showed that MHE inhibited the binding of MvfR the correspondingpqsApromoter region, suggesting that MHE serves as a competitive agent to quench the QS functionality inP. aeruginosa.ConclusionWe prove that MHE functions as an effective countermeasure against bacterial infections.