Quercetin Influences Quorum Sensing in Food Borne Bacteria: In-Vitro and In-Silico Evidence.

Quorum sensing (QS) plays a vital role in regulating the virulence factor of many food borne pathogens, which causes severe public health risk. Therefore, interrupting the QS signaling pathway may be an attractive strategy to combat microbial infections. In the current study QS inhibitory activity of quercetin and its anti-biofilm property was assessed against food-borne pathogens using a bio-sensor strain. In addition in-silico techniques like molecular docking and molecular dynamics simulation studies were applied to screen the quercetin's potentiality as QS inhibitor. Quercetin (80 μg/ml) showed the significant reduction in QS-dependent phenotypes like violacein production, biofilm formation, exopolysaccharide (EPS) production, motility and alginate production in a concentration-dependent manner. Synergistic activity of conventional antibiotics with quercetin enhanced the susceptibility of all tested pathogens. Furthermore, Molecular docking analysis revealed that quercetin binds more rigidly with LasR receptor protein than the signaling compound with docking score of -9.17 Kcal/mol. Molecular dynamics simulation predicted that QS inhibitory activity of quercetin occurs through the conformational changes between the receptor and quercetin complex. Above findings suggest that quercetin can act as a competitive inhibitor for signaling compound towards LasR receptor pathway and can serve as a novel QS-based antibacterial/anti-biofilm drug to manage food-borne pathogens

Caveolin-1 scaffolding domain peptide regulates glucose metabolism in lung fibrosis

Increased metabolism distinguishes myofibroblasts or fibrotic lung fibroblasts (fLfs) from the normal lung fibroblasts (nLfs). The mechanism of metabolic activation in fLfs has not been fully elucidated. Furthermore, the antifibrogenic effects of caveolin-1 scaffolding domain peptide CSP/CSP7 involving metabolic reprogramming in fLfs are unclear. We therefore analyzed lactate and succinate levels, as well as the expression of glycolytic enzymes and hypoxia inducible factor-1α (HIF-1α). Lactate and succinate levels, as well as the basal expression of glycolytic enzymes and HIF-1α, were increased in fLfs. These changes were reversed following restoration of p53 or its transcriptional target microRNA-34a (miR-34a) expression in fLfs. Conversely, inhibition of basal p53 or miR-34a increased glucose metabolism, glycolytic enzymes, and HIF-1α in nLfs. Treatment of fLfs or mice having bleomycin- or Ad-TGF-β1–induced lung fibrosis with CSP/CSP7 reduced the expression of glycolytic enzymes and HIF-1α. Furthermore, inhibition of p53 or miR-34a abrogated CSP/CSP7-mediated restoration of glycolytic flux in fLfs in vitro and in mice with pulmonary fibrosis and lacking p53 or miR-34a expression in fibroblasts in vivo. Our data indicate that dysregulation of glucose metabolism in fLfs is causally linked to loss of basal expression of p53 and miR-34a. Treatment with CSP/CSP7 constrains aberrant glucose metabolism through restoration of p53 and miR-34a

Quorum sensing bioassay of quercetin at different concentration (20, 40 and 80μg /ml) showing inhibition of OHL mediated violacein inhibition.

<p>Quorum sensing bioassay of quercetin at different concentration (20, 40 and 80μg /ml) showing inhibition of OHL mediated violacein inhibition.</p

Details of docked complex of LasR receptor protein with N-octanoyl-DL-homoserine lactone (OHL).

<p>Details of docked complex of LasR receptor protein with N-octanoyl-DL-homoserine lactone (OHL).</p

Residues of LasR receptor protein interacting with quercetin and N-octanoyl-DL-homoserine lactone (OHL) through various interactions.

<p>Residues of LasR receptor protein interacting with quercetin and N-octanoyl-DL-homoserine lactone (OHL) through various interactions.</p

Homology analysis of LasR and YenR gene using clustal W global alignment.

<p>Intensity bar shows the similarity between the sequences. *Represents the identical nucleotides.</p

Synergistic effect of quercetin with antibiotics against food-borne pathogens.

<p>Synergistic effect of quercetin with antibiotics against food-borne pathogens.</p

Quantitative analysis for inhibition of biofilm formation in test strains by quercetin at different concentration (0–40μg/ml).

<p>Data represented were mean of triplicate values with standard deviation. Same letters in the column are not significantly different (p< 0.05).</p