两种肉桂酸衍生物作为铜绿假单胞菌las和pqs群体感应系统的抑制剂：对生物膜形成和毒力因子的影响
Two cinnamic acid derivatives as inhibitors of Pseudomonas aeruginosa las and pqs quorum-sensing systems: Impact on biofilm formation and virulence factors.
作者信息
Leitão Miguel M, Gonçalves Ariana S C, Sousa Sérgio F, Borges Fernanda, Simões Manuel, Borges Anabela
机构信息
LEPABE-Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, s/n, Porto 4200-465, Portugal; ALICE-Associate Laboratory for Innovation in Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, s/n, Porto 4200-465, Portugal; CIQUP-IMS-Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Rua do Campo Alegre, Porto 4169-007, Portugal.
LEPABE-Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, s/n, Porto 4200-465, Portugal; ALICE-Associate Laboratory for Innovation in Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, s/n, Porto 4200-465, Portugal; Environmental Health Department, Portuguese National Health Institute Doctor Ricardo Jorge, Porto, Portugal.
出版信息
Biomed Pharmacother. 2025 Jun;187:118090. doi: 10.1016/j.biopha.2025.118090. Epub 2025 May 2.
INTRODUCTION
Quorum sensing (QS) is a bacterial communication mechanism that regulates gene expression, playing a crucial role in various physiological processes. Interfering with this signalling pathway is a promising strategy to control bacterial pathogenicity and virulence.
OBJECTIVES
This study evaluated the potential of two cinnamic acid derivatives, ferulic and sinapic acids, to inhibit the las and pqs systems in Pseudomonas aeruginosa. Their effects on biofilm architecture, virulence factor production and bacterial motility were also investigated.
METHODS
Bioreporter strains and bioluminescence-based assays were used to evaluate the modulation of QS-activity by cinnamic acid-type phenolic acids. In addition, in silico docking analysis was performed to validate the binding interactions of the cinnamic acid derivatives with QS-receptors. The biofilm architecture was analysed by optical coherence tomography, and virulence factors production (pyoverdine, pyocyanin, total proteases, lipases, gelatinases and siderophores) and motility were measured by absorbance measurement and plate agar method.
RESULTS
Ferulic and sinapic acids at 1000 µg mL inhibited the las and pqs systems by 90 % and 80 %, respectively. The N-3-oxododecanoyl-homoserine lactone production was reduced by 70 % (6.25 µg mL¹). In silico analysis demonstrated that cinnamic acid derivatives exhibited comparable interactions and higher docking scores than reference ligands and inhibitors. Biofilm thickness decreased from 96 µm to 11 µm, and virulence factors and swarming motility were significantly impaired. The comparable anti-QS activity of cinnamic acid derivatives suggests that the additional methoxy group in sinapic acid does not directly contribute to its anti-QS effect.
CONCLUSION
Ferulic and sinapic acids compromised the biofilm architecture and virulence of P. aeruginosa through QS inhibition.
引言
群体感应（QS）是一种细菌通讯机制，可调节基因表达，在各种生理过程中发挥关键作用。干扰这一信号通路是控制细菌致病性和毒力的一种有前景的策略。
目的
本研究评估了两种肉桂酸衍生物，即阿魏酸和芥子酸，抑制铜绿假单胞菌中las和pqs系统的潜力。还研究了它们对生物膜结构、毒力因子产生和细菌运动性的影响。
方法
使用生物报告菌株和基于生物发光的测定法来评估肉桂酸型酚酸对QS活性的调节作用。此外，进行了计算机对接分析，以验证肉桂酸衍生物与QS受体的结合相互作用。通过光学相干断层扫描分析生物膜结构，并通过吸光度测量和平板琼脂法测量毒力因子产生（绿脓菌素、绿脓杆菌素、总蛋白酶、脂肪酶、明胶酶和铁载体）和运动性。
结果
1000μg/mL的阿魏酸和芥子酸分别将las和pqs系统抑制了90%和80%。N-3-氧代十二烷酰高丝氨酸内酯的产生减少了70%（6.25μg/mL）。计算机分析表明，肉桂酸衍生物表现出与参考配体和抑制剂相当的相互作用和更高的对接分数。生物膜厚度从96μm降至11μm，毒力因子和群体运动性显著受损。肉桂酸衍生物相当的抗QS活性表明，芥子酸中额外的甲氧基并不直接有助于其抗QS作用。
结论
阿魏酸和芥子酸通过抑制QS破坏了铜绿假单胞菌的生物膜结构和毒力。
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