Department of Chemistry, School of Advanced Sciences, Vellore Institute of Technology, Vellore, Tamil Nadu, India.
Medical Biotechnology Laboratory, Pushpagiri Research Centre, Pushpagiri Institute of Medical Sciences and Research Centre, Thiruvalla, Kerala, India.
J Appl Microbiol. 2022 Aug;133(2):385-399. doi: 10.1111/jam.15565. Epub 2022 Apr 18.
The incidence of biofilm linked catheter-associated urinary tract infections is increasing worldwide and Pseudomonas aeruginosa is one of the major causes. Perillaldehyde (PLD): as a natural, widely used flavouring agent, has been reported to possess various pharmacological properties. We hypothesized that PLD can inhibit biofilm formation and virulence factor (VF) production by P. aeruginosa by hampering the quorum sensing (QS) system(s).
Minimum inhibitory concentration (MIC) of PLD was assessed for standard strain and two multi-drug resistant catheter isolates of P. aeruginosa utilizing the microdilution method. Microtiter plate assay, crystal violet staining and scanning electron microscopy were used to evaluate the biofilm inhibition property. CFU was utilized to assess the antifouling property of PLD. Detection of VFs and expression analysis of virulence determinants were applied to investigate the anti-virulence activity. Gene expression and molecular docking studies were also executed to explore the QS inhibition and binding of PLD with QS receptors. In the present study, PLD has significantly inhibited biofilm formation and antivirulence activity at sub-MIC levels (2.5 and 3.5 mM) in all the tested strains. In addition, molecular docking studies revealed a significant affinity towards QS receptors.
Perillaldehyde, being a non-toxic food flavouring agent, significantly inhibited biofilm formation and exhibited antifouling property. PLD exhibited significantly reduced levels of VFs (p < 0.001) and their respective genetic determinants (p < 0.001). Gene expression analysis and molecular docking studies confirmed the interactions of PLD to the QS receptors, indicating the plausible mechanism for the anti-virulence property.
This study identified the anti-virulence potential of PLD and provided mechanistic insights. PLD can be a suitable, non-toxic candidate for countering biofilms and associated pathogens, contributing to the prevention of biofilm-associated nosocomial infections.
生物膜相关的导管相关性尿路感染的发病率在全球范围内不断上升，铜绿假单胞菌是主要原因之一。紫苏醛（PLD）：作为一种天然的、广泛使用的调味剂，已被报道具有多种药理特性。我们假设 PLD 可以通过干扰群体感应（QS）系统来抑制铜绿假单胞菌的生物膜形成和毒力因子（VF）的产生。
采用微量稀释法评估 PLD 对标准株和两种多药耐药导管分离株铜绿假单胞菌的最低抑菌浓度（MIC）。采用微量滴定板法、结晶紫染色和扫描电子显微镜评估生物膜抑制特性。利用 CFU 评估 PLD 的防污性能。检测 VFs 并应用表达分析毒力决定因素，以研究抗毒力活性。还进行了基因表达和分子对接研究，以探索 QS 抑制和 PLD 与 QS 受体的结合。在本研究中，PLD 在所有测试菌株的亚 MIC 水平（2.5 和 3.5 mM）下显著抑制生物膜形成和抗病毒活性。此外，分子对接研究显示对 QS 受体具有显著的亲和力。
紫苏醛作为一种无毒的食品调味剂，可显著抑制生物膜形成，并表现出防污特性。PLD 显著降低了 VFs（p < 0.001）及其各自遗传决定因素（p < 0.001）的水平。基因表达分析和分子对接研究证实了 PLD 与 QS 受体的相互作用，表明了抗毒力特性的可能机制。
本研究确定了 PLD 的抗病毒潜力，并提供了机制见解。PLD 可以作为一种合适的、无毒的候选药物，用于对抗生物膜和相关病原体，有助于预防生物膜相关的医院感染。
