Effects of 14-alpha-lipoyl andrographolide on quorum sensing in Pseudomonas aeruginosa.
In Pseudomonas aeruginosa, the quorum-sensing (QS) system is closely related to biofilm formation. We previously demonstrated that 14-alpha-lipoyl andrographolide (AL-1) has synergistic effects on antibiofilm and antivirulence factors (pyocyanin and exopolysaccharide) of P. aeruginosa when combined with conventional antibiotics, while it has little inhibitory effect on its growth. However, its molecular mechanism remains elusive. Here we investigated the effect of AL-1 on QS systems, especially the Las and Rhl systems. This investigation showed that AL-1 can inhibit LasR-3-oxo-C(12)-homoserine lactone (HSL) interactions and repress the transcriptional level of QS-regulated genes. Reverse transcription (RT)-PCR data showed that AL-1 significantly reduced the expression levels of lasR, lasI, rhlR, and rhlI in a dose-dependent manner. AL-1 not only decreased the expression level of Psl, which is positively regulated by the Las system, but also increased the level of secretion of ExoS, which is negatively regulated by the Rhl system, indicating that AL-1 has multiple effects on both the Las and Rhl systems. It is no wonder that AL-1 showed synergistic effects with other antimicrobial agents in the treatment of P. aeruginosa infections.
Chinese Academy of Sciences, Beijing, China.
Li
L
Ma
Xiangyang
X
Liu
Haihua
H
Liang
Yizhou
Y
Che
Caixia
C
Chen
Huanqin
H
Dai
Ke
K
Yu
Mei
M
Liu
Luyan
L
Ma
Ching-Hong
CH
Yang
Fuhang
F
Song
Yuqiang
Y
Wang
Lixin
L
Zhang
D035685:Andrographis / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000187:drug effects / Q000235:genetics; D018441:Biofilms / Q000187:drug effects; D015153:Blotting, Western; D004224:Diterpenes / Q000494:pharmacology; D004357:Drug Synergism; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D007202:Indicators and Reagents; D008156:Luciferases / Q000235:genetics; D008826:Microbial Sensitivity Tests; D011134:Polysaccharides / Q000737:chemistry; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000378:metabolism; D016958:Pseudomonas putida / Q000187:drug effects; D053038:Quorum Sensing / Q000187:drug effects*; D060888:Real-Time Polymerase Chain Reaction; D015534:Trans-Activators / Q000187:drug effects / Q000235:genetics; D001616:beta-Galactosidase / Q000737:chemistry
C578526:14-lipoylandrographolide; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004224:Diterpenes; D007202:Indicators and Reagents; C080365:LasR protein, Pseudomonas aeruginosa; D011134:Polysaccharides; D015534:Trans-Activators; D008156:Luciferases; D001616:beta-Galactosidase