Paeonol Interferes With Quorum-Sensing in Pseudomonas aeruginosa and Modulates Inflammatory Responses In Vitro and In Vivo

Abstract

Developing quorum-sensing (QS) based anti-infection drugs is one of the most powerful strategies to combat multidrug-resistant bacteria. Paeonol has been proven to attenuate the QS-controlled virulence factors of <i>P. aeruginosa</i> by down-regulating the transcription of QS signal molecules. This research aimed to assess the anti-virulence activity and mechanism of paeonol against <i>P. aeruginosa</i> infection <i>in vitro</i> and <i>in vivo</i>. In this study, paeonol was found to reduce the adhesion and invasion of <i>P.aeruginosa</i> to macrophages and resist the cytotoxicity induced by <i>P.aeruginosa</i>. Paeonol reduced the expression of virulence factors of <i>P.aeruginosa</i> by inhibiting QS, thereby reducing the LDH release and damage of <i>P.aeruginosa</i>-infected macrophages. Paeonol can inhibit bacterial virulence and enhance the ability of macrophages to clear <i>P.aeruginosa</i>. In addition, paeonol exerts anti-inflammatory activity by reducing the expression of inflammatory cytokines and increasing the production of anti-inflammatory cytokines. Paeonol treatment significantly inhibited the activation of TLR4/MyD88/NF-κB signaling pathway and decreased the inflammation response of <i>P. aeruginosa</i>-infected macrophages. Paeonol also significantly reduced the ability of <i>P.aeruginosa</i> to infect mice and reduced the inflammatory response. These data suggest that paeonol can inhibit the virulence of <i>P.aeruginosa</i> and decrease the inflammation response in <i>P.aeruginosa</i>-infected macrophages and mice, which can decrease the damage induced by <i>P.aeruginosa</i> infection and enhance the ability of macrophages to clear bacteria. This study supports the further development of new potential anti-infective drugs based on inhibition of QS and virulence factors.