Abstract
As the antibiotic resistance of pathogens becomes increasingly severe, it is becoming more feasible to use methods that suppress the virulence of pathogens rather than exerting selective pressure on their growth. Pseudomonas aeruginosa, a dangerous opportunistic pathogen, infects hosts by producing multiple virulence factors, which are regulated by quorum-sensing (QS) systems, including the las systems, rhl systems, and pqs systems. This study used the chromosome lacZ transcription fusion reporter model to screen the traditional Chinese medicine monomer library and found that bakuchiol can effectively inhibit the pqs system and related virulence phenotypes of P. aeruginosa, including the production of virulence factors (pyocyanin, hydrogen cyanide, elastase, and lectin) and motility (swarming, swimming, and twitching motility) without affecting its growth. Subsequently, through genetic complementation analysis, we found that bakuchiol inhibited the function of the transcriptional activation protein PqsR of the pqs system in P. aeruginosa in a concentration-dependent manner. Furthermore, molecular dynamics simulation study results indicated that bakuchiol can target PqsR of the pqs system, thereby inhibiting the pqs system. Among the amino acids in PqsR, ALA-168 may be a key amino acid residue in the hydrophobic interaction between PqsR protein and bakuchiol. Finally, in vivo experiments demonstrated that bakuchiol attenuated the pathogenicity of P. aeruginosa to Chinese cabbage (Brassica pekinensis) and Caenorhabditis elegans. In summary, this study suggests that bakuchiol is an effective inhibitor that targets the pqs system of P. aeruginosa, providing a new strategy for addressing P. aeruginosa infections.