Abstract

Honey is an excellent source of polyphenolic compounds that are effective in attenuating quorum sensing (QS), a chemical process of cell-to-cell communication system used by the opportunistic pathogen Pseudomonas aeruginosa to regulate virulence and biofilm formation. However, lower water solubility and inadequate bioavailability remains major concerns of these therapeutic polyphenols. Its therapeutic index can be improved by using nano-carrier systems to target QS signaling potently. In the present study, we fabricated a unique drug delivery system comprising selenium nanoparticles (SeNPs; non-viral vectors) and polyphenols of honey (HP) for enhancement of anti-QS activity of HP against P. aeruginosa PAO1. The developed selenium nano-scaffold showed superior anti-QS activity, anti-biofilm efficacy, and anti-virulence potential in both in-vitro and in-vivo over its individual components, SeNPs and HP. LasR is inhibited by selenium nano-scaffold in-vitro. Using computational molecular docking studies, we have also demonstrated that the anti-virulence activity of selenium nano-scaffold is reliant on molecular binding that occurs between HP and the QS receptor LasR through hydrogen bonding and hydrophobic interactions. Our preliminary investigations with selenium-based nano-carriers hold significant promise to improve anti-virulence effectiveness of phytochemicals by enhancing effective intracellular delivery.

Highlights

  • Emergence of multi-drug resistant bacteria has driven studies for disabling virulence preferentially through quorum sensing (QS) inhibition tactics instead of bactericidal and bacteriostatic strategies (Singh et al, 2009a; Defoirdt et al, 2013; Kim et al, 2015; Lidor et al, 2015; Srivastava et al, 2015; Wang et al, 2015; Yang et al, 2015)

  • We look forward to design the scaffold of selenium nanoparticles (SeNPs) and phytochemicals of honey (HP; anti-QS agents), conjugated on the surface of SeNPs (SeNPs@HP)

  • After incubation of sodium selenite with HP for 30 min, the sample solution was harvested for the transmission electron microscopy (TEM) analysis

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Summary

Introduction

Emergence of multi-drug resistant bacteria has driven studies for disabling virulence preferentially through quorum sensing (QS) inhibition tactics instead of bactericidal and bacteriostatic strategies (Singh et al, 2009a; Defoirdt et al, 2013; Kim et al, 2015; Lidor et al, 2015; Srivastava et al, 2015; Wang et al, 2015; Yang et al, 2015). P. aeruginosa, a Gram-negative bacterium causes cystic fibrosis in immunocompromised patients, burn units of hospitals, and in implanted medical. Quorum Sensing Nano-Inhibitors devices including intubation tubes and stents It is lethal to cystic fibrosis patients (common genetic disorder in Caucasians) by developing mucoid in lung tissue leading to pneumonia. The current anti-QS therapies often are not straightforward owing to their lower bioavailability and inadequate penetration of bacterial biofilm and results in significant casualties (Defoirdt et al, 2013).The development of a novel series of bio-nanomaterials for efficient drug delivery opens a new prospective to rectify these problems

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