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 Chromobacterium violaceum 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 Pseudomonas aeruginosa. A Caenorhabditis elegans infection model was used to explore the anti-infection ability of paeonol in vivo. 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 P. aeruginosa 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 P. aeruginosa including lasI/R, rhlI/R, pqs/mvfR, as well as mediated its virulence factors, lasA, lasB, rhlA, rhlC, phzA, phzM, phzH, and phzS. In vivo studies revealed that paeonol could reduce the pathogenicity of P. aeruginosa and enhance the survival rate of C. elegans, showing a moderate protective effect on C. elegans. Collectively, these findings suggest that paeonol attenuates bacterial virulence and infection of P. aeruginosa and that further research elucidating the anti-QS mechanism of this compound in vivo is warranted.

Inhibition of Virulence Factors and Biofilm Formation by Wogonin Attenuates Pathogenicity of Pseudomonas aeruginosa PAO1 via Targeting pqs Quorum-Sensing System

“…Therefore, in the following study, 70% ethanol extracts of A. pilosa were used. Sd the QS system regulates most of the virulence factors and pathogenicity [ 7 , 23 ], we further examined the effects of the extracts from A. pilosa on the virulence phenotypes of PAO1.The virulence-related phenotypes, including motility (twitching, swimming, and swarming), elastase and pyocyanin production, and biofilm formation, were reduced when different concentrations of the 70% ethanol extracts of A. pilosa were used ( Figure 1 B). The pathogenicity detection by the Chinese cabbage model showed that the decay area gradually became small with the increase of the extract concentrations of A. pilosa ( Figure S1 ).…”

“…For example, the extracts from the mixture of Artemisiae argyi folium, the root bark of Cortex dictamni , and the root of Solanum melongena could completely inhibit pqs system of P. aeruginosa [ 21 ]. Paeonol from peony root interfered with las system, reduced virulence production, and inhibited biofilm formation [ 23 ]. Coumarin, a Chinese medicinal herb-derived phenolic compound, reduced protease and pyocyanin production and inhibited biofilm formation of different P. aeruginosa strains by impairing QS systems and changing cyclic diguanylate (c-di-GMP) metabolism [ 33 ].…”

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

“…PAO1 significantly inhibited macrophages cell proliferation, induced cytotoxic responses, and led to cell membrane damage and rupture, lysis, and death. Our former studies had revealed that paeonol could attenuate quorum-sensing regulated virulence and biofilm formation in P. aeruginosa and show a protective effect on C. elegans infected with P. aeruginosa in vivo ( 28 ). Here, the potential therapeutic effect and mechanism of paeonol were investigated in a macrophage infected with a PAO1 cell model.…”

“…Paeonol is a polyphenolic compound originally extracted from Paeonia lactiflora , Moutan cortex , and Cynanchum paniculatum , which has been used wildly due to various medicinal benefits as an analgesic, antipyretic, and anti-inflammatory agent in traditional Chinese medicine ( 26 , 27 ). Previous studies have demonstrated that paeonol attenuates quorum-sensing, inhibits virulence factors, and biofilm formation ( 28 ). Paeonol has been well-documented for revealing potential anti-inflammatory activity in macrophages ( 29 , 30 ), but the possible mechanism by regulating virulence and inflammation to reduce pathological damage upon pathogenic P. aeruginosa infection has not yet been fully studied in vitro and in vivo .…”

Epigallocatechin-3-Gallate Ameliorates Acute Lung Damage by Inhibiting Quorum-Sensing-Related Virulence Factors of Pseudomonas aeruginosa

“…The qRT-PCR reaction was conducted on a LightCycler ® 480II Master Mix (Roche, Germany). Data from qRT-PCR experiments were analyzed using the 2 ®-ΔΔCT method ( Yang et al, 2021 ). Primer sequences are listed in Table 1 .…”