Embelia ribes Burm.f. fruit extract inhibit quorum sensing-dependent production of virulence factors and biofilm formation: An integrated in vitro and in silico approach

Abstract

Quorum sensing (QS) is a cell-to-cell signaling method that allows bacteria to control gene expression and regulate a variety of physiological processes, particularly the synthesis of virulence factors and biofilm formation. Inhibition of QS has been proposed as a promising strategy in attenuating the pathogenicity and enhancing the efficacy of antimicrobial drugs targeting bacterial infections. This study investigated the potential utilization of Embelia ribes fruit extract (ERFE) as an inhibitor of QS-dependent virulence factors and biofilm development in Gram negative pathogens. Further, the results were correlated with the inhibition of biofilms. High performance thin-layer chromatography (HPTLC), followed by analysis of phytochemicals using gas chromatography-mass spectrometry (GC–MS) was conducted. Analyzing ADMET (absorption, distribution, metabolism, excretion and toxicity) profiles, PAINS (Pan-assay interference compounds), and molecular docking analyses of selected potential phytochemicals were performed against proteins participating in QS and formation of biofilm. In-vitro analysis of anti-QS activity of ERFE against Chromobacterium violaceum (violacein production), Pseudomonas aeruginosa (pyocyanin production) and Serratia marcescens (prodigiosin production) demonstrated significant dose-dependent interference in pigment formation at sub-MIC concentrations. The development of biofilm was significantly reduced by 84.10, 85.52 and 70.64% over control at the highest sub-MIC levels for C. violaceum, P. aeruginosa and S. marcescens, respectively. Furthermore, in the presence of ERFE, swarming motility and exopolysaccharide production (EPS) were also reduced. As a result, further insights have been gained into the mechanism underlying the anti-QS activity. Further investigations with in-vivo studies are warranted to fully explore the therapeutic applications of this natural compound in managing the bacterial pathogenicity and biofilm-related infections.