Abstract
The emergence of multi-drug resistance in pathogenic bacteria in clinical settings as well as food-borne infections has become a serious health concern. The problem of drug resistance necessitates the need for alternative novel therapeutic strategies to combat this menace. One such approach is targeting the quorum-sensing (QS) controlled virulence and biofilm formation. In this study, we first screened different fractions of Psoralea corylifolia (seed) for their anti-QS property in the Chromobacterium violaceum 12472 strain. The methanol fraction was found to be the most active fraction and was selected for further bioassays. At sub-inhibitory concentrations, the P. corylifolia methanol fraction (PCMF) reduced QS-regulated virulence functions in C. violaceum CVO26 (violacein); Pseudomonas aeruginosa (elastase, protease, pyocyanin, chitinase, exopolysaccharides (EPS), and swarming motility), A. hydrophila (protease, EPS), and Serratia marcescens (prodigiosin). Biofilm formation in all the test pathogens was reduced significantly (p ≤ 0.005) in a concentration-dependent manner. The β-galactosidase assay showed that the PCMF at 1,000 μg/ml downregulated las-controlled transcription in PAO1. In vivo studies with C. elegans demonstrated increased survival of the nematodes after treatment with the PCMF. Bakuchiol, a phytoconstituent of the extract, demonstrated significant inhibition of QS-regulated violacein production in C. violaceum and impaired biofilm formation in the test pathogens. The molecular docking results suggested that bakuchiol efficiently binds to the active pockets of LasR and RhlR, and the complexes were stabilized by several hydrophobic interactions. Additionally, the molecular dynamics simulation of LasR, LasR–bakuchiol, RhlR, and RhlR–bakuchiol complexes for 50 ns revealed that the binding of bakuchiol to LasR and RhlR was fairly stable. The study highlights the anti-infective potential of the PCMF and bakuchiol instead of bactericidal or bacteriostatic action, as the extract targets QS-controlled virulence and the biofilm.
Highlights
Quorum sensing (QS) is a density-dependent phenomenon facilitating the coordinated regulation of gene expression in bacteria (Winans and Bassler, 2002)
Different fractions of P. corylifolia obtained in petroleum ether, benzene, ethyl acetate, acetone, and methanol were tested for their QS modulatory activity at varying concentrations against the C. violaceum ATCC 12472 (CV12472) strain
Fractionbased anti-QS activity against C. violaceum ATCC 12472 was demonstrated by the P. corylifolia methanol extract at 400 and 800 μg/ml concentrations, while at 1,600 μg/ml, pigment inhibition was accompanied by the inhibition of growth
Summary
Quorum sensing (QS) is a density-dependent phenomenon facilitating the coordinated regulation of gene expression in bacteria (Winans and Bassler, 2002). Interfering with the bacterial communication forces the bacteria to reside as individuals fending for themselves, whereas the bacteria residing and functioning as a group build strong defense that an individual bacterium finds impossible to achieve (Rasmussen and Givskov, 2006). This strategy of targeting the functions of bacteria that are responsible for pathogenesis rather than growth have been termed as “antivirulence” or “antipathogenesis” therapies (LaSarre and Federle, 2013; de la Fuente-Núñez et al, 2014)
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