Abstract：
Among the ESKAPE pathogens, Pseudomonas aeruginosa is an extensively notorious superbug that causes difficult-to-treat infections. Since quorum sensing (QS) directly promotes pseudomonal virulence, targeting QS circuits is a promising approach for disarming phenotypic virulence. Hence, this study scrutinizes the anti-QS, antivirulence, and anti-biofilm potential of citral (CiT; phytochemical) and triclosan (TcN; disinfectant), alone and in combination, against P. aeruginosa PAO1/PA14. The findings confirmed synergism between CiT and TcN and revealed their quorum quenching (QQ) potential. At sub-inhibitory levels, CiT-TcN combination significantly impeded pyocyanin, total bacterial protease, hemolysin, and pyochelin production alongside inhibiting biofilm formation in P. aeruginosa. Moreover, the QQ and antivirulence potential of CiT and TcN was positively correlated by molecular docking studies that predicted strong associations of the drugs with QS receptors of P. aeruginosa. Collectively, the study identifies CiT-TcN as an effective drug combination that harbors QQ, antivirulence, and anti-biofilm prospects against P. aeruginosa.
摘要：
在ESKAPE病原体中，铜绿假单胞菌是一种广为人知的超级细菌，可导致难以治疗的感染。由于群体感应(QS)直接促进假单胞菌毒力，靶向QS电路是解除表型毒力的一种有前途的方法。因此，这项研究仔细检查了反QS，抗毒力,柠檬醛（CiT;植物化学）和三氯生（TcN;消毒剂）的抗生物膜潜力，单独和组合，针对铜绿假单胞菌PAO1/PA14。研究结果证实了CiT和TcN之间的协同作用，并揭示了它们的群体猝灭（QQ）潜力。在亚抑制水平，CiT-TcN组合显着阻碍了绿脓苷，总细菌蛋白酶，溶血素,和pytochelin的产生以及抑制铜绿假单胞菌中生物膜的形成。此外，通过分子对接研究，预测药物与铜绿假单胞菌QS受体的强关联，CiT和TcN的QQ和抗毒力潜力呈正相关。总的来说，该研究将CiT-TcN确定为含有QQ的有效药物组合，抗毒力,和抗生物膜的前景。
