Paeonol Attenuates Quorum-Sensing Regulated Virulence and Biofilm Formation in Pseudomonas aeruginosa

Abstract

With the prevalence of multidrug-resistant bacteria and clinical -acquired pathogenic infections, the development of quorum-sensing (QS) interfering agents is one of the most potential strategies to combat bacterial infections and antibiotic resistance. Chinese herbal medicines constitute a valuable bank of resources for the identification of QS inhibitors. Accordingly, in this research, some compounds were tested for QS inhibition using indicator strains. Paeonol is a phenolic compound, which can effectively reduce the production of violacein without affecting its growth in <i>Chromobacterium violaceum</i> ATCC 12472, indicating its excellent anti-QS activity. This study assessed the anti-biofilm activity of paeonol against Gram-negative pathogens and investigated the effect of paeonol on QS-regulated virulence factors in <i>Pseudomonas aeruginosa</i>. A <i>Caenorhabditis elegans</i> infection model was used to explore the anti-infection ability of paeonol <i>in vivo</i>. Paeonol exhibited an effective anti-biofilm activity against Gram-negative bacteria. The ability of paeonol to interfere with the AHL-mediated quorum sensing systems of <i>P. aeruginosa</i> was determined, found that it could attenuate biofilm formation, and synthesis of pyocyanin, protease, elastase, motility, and AHL signaling molecule in a concentration- and time-dependent manner. Moreover, paeonol could significantly downregulate the transcription level of the QS-related genes of <i>P. aeruginosa</i> including <i>lasI/R, rhlI/R, pqs/mvfR</i>, as well as mediated its virulence factors, <i>lasA, lasB, rhlA, rhlC, phzA, phzM, phzH</i>, and <i>phzS</i>. <i>In vivo</i> studies revealed that paeonol could reduce the pathogenicity of <i>P. aeruginosa</i> and enhance the survival rate of <i>C. elegans</i>, showing a moderate protective effect on <i>C. elegans</i>. Collectively, these findings suggest that paeonol attenuates bacterial virulence and infection of <i>P. aeruginosa</i> and that further research elucidating the anti-QS mechanism of this compound <i>in vivo</i> is warranted.