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丁香酚通过与群体感应受体竞争性结合而表现出抗毒力特性。

Eugenol exhibits anti-virulence properties by competitively binding to quorum sensing receptors.

作者信息

Rathinam Prasanth, Vijay Kumar H S, Viswanathan Pragasam

机构信息

a Renal Research Lab, Centre for Bio-Medical Research, School of Bio-Sciences and Technology , VIT University , Vellore , India.

b Department of Biotechnology , Maharani Lakshmi Ammanni College for Women , Bangalore , India.

出版信息

Biofouling. 2017 Sep;33(8):624-639. doi: 10.1080/08927014.2017.1350655. Epub 2017 Aug 9.

DOI:10.1080/08927014.2017.1350655
PMID:28792229
Abstract

The primary objective of this study was to ascertain the anti-biofilm and anti-virulence properties of sub-minimum inhibitory concentration (MIC) levels of eugenol against the standard strain PAO1 and two multi-drug resistant P. aeruginosa clinical isolates utilizing quorum sensing inhibition (QSI). Eugenol at 400 μM significantly reduced biofilm formation on urinary catheters and the virulence factors (VF) including extracellular polysaccharides, rhamnolipid, elastase, protease, pyocyanin, and pyoverdine (p < 0.001). Further, eugenol exhibited a marked effect on the production of QS signals (AIs) (p < 0.001) without affecting their chemical integrity. In silico docking studies demonstrated a stable molecular binding between eugenol and QS receptor(s) in comparison with respective AIs. Investigation on reporter strains confirmed the competitive binding of eugenol to a QS receptor (LasR) as the possible QSI mechanism leading to significant repression of QS associated genes besides the VF genes (p < 0.001). This study provides insights, for the first time, into the mechanism of the anti-virulence properties of eugenol.

摘要

本研究的主要目的是确定丁香酚低于最低抑菌浓度(MIC)水平对标准菌株PAO1和两株多重耐药铜绿假单胞菌临床分离株的抗生物膜和抗毒力特性,采用群体感应抑制(QSI)方法。400μM的丁香酚显著减少了导尿管上生物膜的形成以及包括胞外多糖、鼠李糖脂、弹性蛋白酶、蛋白酶、绿脓菌素和绿脓杆菌荧光素在内的毒力因子(VF)(p<0.001)。此外,丁香酚对群体感应信号(AIs)的产生有显著影响(p<0.001),且不影响其化学完整性。计算机对接研究表明,与各自的AIs相比,丁香酚与群体感应受体之间存在稳定的分子结合。对报告菌株的研究证实,丁香酚与群体感应受体(LasR)的竞争性结合是可能的群体感应抑制机制,除了毒力因子基因外,还导致群体感应相关基因的显著抑制(p<0.001)。本研究首次深入探讨了丁香酚抗毒力特性的机制。

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