Falcarindiol Isolated from Inhibits the Quorum Sensing of

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2021 Oct 13

PMID 34641440

Citations 9

Authors

Chaoyue Zhao

Hongda Zheng

Liman Zhou

Hongrui Ji

Lu Zhao

Wengong Yu

Qianhong Gong

Affiliations

Soon will be listed here.

Abstract

Quorum sensing (QS) is employed by the opportunistic pathogen to regulate physiological behaviors and virulence. QS inhibitors (QSIs) are potential anti-virulence agents for the therapy of infection. During the screening for QSIs from Chinese herbal medicines, falcarindiol (the major constituent of ) exhibited QS inhibitory activity. The subinhibitory concentration of falcarindiol exerted significant inhibitory effects on the formation of biofilm and the production of virulence factors such as elastase, pyocyanin, and rhamnolipid. The mRNA expression of QS-related genes (, , , , , , and ) was downregulated by falcarindiol while that of was not affected by falcarindiol. The transcriptional activation of the promoter was inhibited by falcarindiol in the QSIS- selector. Further experiments confirmed that falcarindiol inhibited the system using the reporter strain MG4/pKDT17. Electrophoretic mobility shift assay (EMSA) showed that falcarindiol inhibited the binding of the transcription factor LasR and the promoter region. Molecular docking showed that falcarindiol interacted with the Tyr47 residue, leading to LasR instability. The decrease of LasR-mediated transcriptional activation was responsible for the reduction of downstream gene expression, which further inhibited virulence production. The inhibition mechanism of falcarindiol to LasR provides a theoretical basis for its medicinal application.

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