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Huang, Xuan‐He; She, Meng‐Ting; Zhang, Yi‐Hang; Liu, Yi‐Fu; Zhong, Dong‐Xiao; Zhang, Yi‐Han; Zheng, Jun‐Xia; Sun, Ning; Wong, Wing‐Leung; Lu, Yu‐Jing
Journal of applied microbiology, October 2022, Volume: 133, Issue: 4Journal Article
Aims The emerging of drug resistant Pseudomonas aeruginosa is a critical challenge and renders an urgent action to discover innovative antimicrobial interventions. One of these interventions is to disrupt the pseudomonas quinolone signal (pqs) quorum sensing (QS) system, which governs multiple virulence traits and biofilm formation. This study aimed to investigate the QS inhibitory activity of a series of new PqsR inhibitors bearing a quinoline scaffold against Ps. aeruginosa. Methods and Results The results showed that compound 1 suppressed the expression of QS‐related genes and showed the best inhibitory activity to the pqs system of wild‐type Ps. aeruginosa PAO1 with an IC50 of 20.22 μmol L−1. The virulence factors including pyocyanin, total protease, elastase and rhamnolipid were significantly suppressed in a concentration‐dependent manner with the compound. In addition, compound 1 in combination with tetracycline inhibited synergistically the bacterial growth and suppressed the biofilm formation of PAO1. The molecular docking studies also suggested that compound 1 could potentially interact with the ligand‐binding domain of the Lys‐R type transcriptional regulator PqsR as a competitive antagonist. Conclusions The quinoline‐based derivatives were found to interrupt the quorum sensing system via the pqs pathway and thus the production of virulence factors was inhibited and the antimicrobial susceptibility of Ps. aeruginosa was enhanced. Significance and Impact of Study The study showed that the quinoline‐based derivatives could be used as an anti‐virulence agent for treating Ps. aeruginosa infections.
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