Cranberry-derived proanthocyanidins impair virulence and inhibit quorum sensing of Pseudomonas aeruginosa

Abstract

Bacteria have evolved multiple strategies for causing infections that include producing virulence factors, undertaking motility, developing biofilms, and invading host cells. N-acylhomoserine lactone (AHL)-mediated quorum sensing (QS) tightly regulates the expression of multiple virulence factors in the opportunistic pathogenic bacterium Pseudomonas aeruginosa. Thus, inhibiting QS could lead to health benefits. In this study, we demonstrate an anti-virulence activity of a cranberry extract rich in proanthocyanidins (cerPAC) against P. aeruginosa in the model host Drosophila melanogaster and show this is mediated by QS interference. cerPAC reduced the production of QS-regulated virulence determinants and protected D. melanogaster from fatal infection by P. aeruginosa PA14. Quantification of AHL production using liquid chromatography-mass spectrometry confirmed that cerPAC effectively reduced the level of AHLs produced by the bacteria. Furthermore, monitoring QS signaling gene expression revealed that AHL synthases LasI/RhlI and QS transcriptional regulators LasR/RhlR genes were inhibited and antagonized, respectively, by cerPAC. Molecular docking studies suggest that cranberry-derived proanthocyanidin binds to QS transcriptional regulators, mainly interacting with their ligand binding sites. These findings provide insights into the underlying mechanisms of action of a cerPAC to restrict the virulence of P. aeruginosa and can have implications in the development of alternative approaches to control infections.

Tart cherry (Prunus cerasus L.) fractions inhibit biofilm formation and adherence properties of oral pathogens and enhance oral epithelial barrier function

“…Such characteristics have been previously reported for extracts from other berry fruits, including cranberry and blueberry (Ben Lagha, Groeger, et al, ; Ben Lagha et al, ; Feldman et al, ; Feghali et al, ). Although we did not investigate the antibiofilm mechanism of the tart cherry fractions, it may be related to their ability to modify the microbial cell surface hydrophobicity, to inhibit the gene expression of adhesins, or to interfere with the quorum sensing, as previously reported for cranberry extracts (Maisuria, Lopez‐de Los Santos, Tufenkji, & Déziel, ; Rafsanjany, Senker, Brandt, Dobrindt, & Hensel, ; Yamanaka, Kimizuka, Kato, & Okuda, ).…”

Application of β-Resorcylic Acid as Potential Antimicrobial Feed Additive to Reduce Campylobacter Colonization in Broiler Chickens

“…It is previously reported that the SIC of antimicrobials modulates the expression of various virulence proteins and associated genes in bacteria thereby resulting in changes in their pathophysiology and virulence (Goh et al, 2002; Tsui et al, 2004; Qiu et al, 2010; Upadhyay et al, 2012, 2014; Maisuria et al, 2016). To study if similar mechanisms exist in Campylobacter , we investigated the effect of BR on various genes of Campylobacter that are known to facilitate colonization in poultry.…”

Proanthocyanidin Interferes with Intrinsic Antibiotic Resistance Mechanisms of Gram‐Negative Bacteria

“…cPAC was an effective potentiator against diverse bacterial lifestyles normally tolerant to antibiotics, such as biofilm bacteria, dormant cells, and in experimental models of chronic infections. [19] Studies suggest that consumption of cranberry Antibiotic resistance is spreading at an alarming rate among pathogenic bacteria in both medicine and agriculture. These results suggest that in combination with antibiotic therapy, cPAC has the potential to decrease the spread of antibiotic resistance and prolong the effectiveness of currently available drugs.…”