Novel quinoline-based derivatives as the PqsR inhibitor against Pseudomonas aeruginosa PAO1

被引:10
作者
Huang, Xuan-He [1 ]
She, Meng-Ting [1 ]
Zhang, Yi-Hang [1 ]
Liu, Yi-Fu [1 ]
Zhong, Dong-Xiao [1 ]
Zhang, Yi-Han [1 ]
Zheng, Jun-Xia [1 ]
Sun, Ning [2 ,3 ]
Wong, Wing-Leung [2 ]
Lu, Yu-Jing [1 ,4 ,5 ]
机构
[1] Guangdong Univ Technol, Sch Biomed & Pharmaceut Sci, Guangzhou 510006, Peoples R China
[2] Hong Kong Polytech Univ, Dept Appl Biol & Chem Technol, State Key Lab Chem Biol & Drug Discovery, Hung Hom, Hong Kong, Peoples R China
[3] South China Univ Technol, Guangzhou Peoples Hosp 1, Sch Med, Guangzhou, Peoples R China
[4] Engn Res Acad High Value Utilizat Green Plants, Meizhou, Peoples R China
[5] Golden Hlth Guangdong Biotechnol Co Ltd, Foshan, Peoples R China
基金
中国国家自然科学基金;
关键词
drug resistance; PqsR inhibitor; Pseudomonas aeruginosa; quinoline derivatives; quorum sensing; virulence factors; ANTI-VIRULENCE STRATEGIES; SWARMING MOTILITY; STATIONARY-PHASE; EXOTOXIN-A; SIGNAL; MULTIDRUG; BIOFILM; GENE; REGULATOR; ELASTASE;
D O I
10.1111/jam.15601
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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 mu mol 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.
引用
收藏
页码:2167 / 2181
页数:15
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