Homogentisic acid γ-lactone suppresses the virulence factors of Pseudomonas aeruginosa by quenching its quorum sensing signal molecules

Homogentisic acid γ-lactone suppresses the virulence factors of Pseudomonas aeruginosa by quenching its quorum sensing signal molecules
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均质龙胆酸 g-内酯通过淬灭铜绿假单胞菌的群体感应信号分子来抑制其毒力因子

DOI:
10.1016/j.cclet.2017.09.052
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发表时间:
2018-02-01
影响因子:
9.1
通讯作者:
Wu, Chunhui
Wu, Chunhui
中科院分区:
化学1区
文献类型:
--
作者:
Li, Shuihong;Leung, Polly H. M.;Wu, Chunhui

文献摘要

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细菌群体感应(quorum sensing,QS)分子参与生物膜形成、毒力和抗生素抗性等行为的协调。QS分子(自身诱导物)及其相应的受体已被认为是耐药感染和生物膜相关感染(BAI)的重要治疗靶点。本研究评估了尿黑酸γ-内酯(HgAL),呋喃酮衍生物的多种生物学效应。结果表明,HgAL能有效抑制铜绿假单胞菌(Pseudomonasaeruginosa)产生绿脓菌素和胞外基质,降低其粘附能力和生物被膜形成。HgAL对铜绿假单胞菌的毒力抑制作用主要是通过抑制3-oxo-C-12-HSL和C-4-HSL(铜绿假单胞菌中的两种QS信号分子)的生物合成来实现的。我们的研究结果支持汞作为一个潜在的代理预防BAI在医疗机构。(C)2017年中国化学会、中国医学科学院药物研究所。Elsevier B.V.出版,保留所有权利。
Bacterial quorum sensing (QS) molecules are involved in the coordination of certain behaviors such as biofilm formation, virulence and antibiotic resistance. QS molecules (autoinducers) and their corresponding receptors have been recognized as important therapeutic targets for drug -resistant infections and biofilm-associated infections (BAI). This study assessed the multiple biological effects of homogentisic acid gamma-lactone (HgAL), a furanone derivative. The anti -QS and anti-biofilm effects of HgAL against PAO1 strain were evaluated using CLSM, SEM, HPLC and other biochemical methods The results showed that HgAL could effectively inhibit the production of pyocyanin and extracellular matrix, as well as reduce the adherence ability and biofilm formation of Pseudomonas aeruginosa. Inhibition of virulence is attributed to the suppressive effect of HgAL on biosynthesis of 3-oxo-C-12-HSL and C-4-HSL (two kinds of QS signaling molecules in P. aeruginosa). Our results support HgAL as a potential agent for prevention of BAI in the healthcare settings. (C) 2017 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.