Layer-By-Layer Coating of Aminocellulose and Quorum Quenching Acylase on Silver Nanoparticles Synergistically Eradicate Bacteria and Their Biofilms

Abstract

The emergence of antibiotic-resistant bacteria and the failure of the existing antibacterial therapeutics call for development of novel treatment strategies. Furthermore, the formation of bacterial biofilms restricts drug penetration and efficiency, causing life-threatening infections. Bacterial attachment and biofilm formation are regulated by the cell-to-cell communication phenomenon called quorum sensing (QS). In this work, antimicrobial silver nanoparticles (AgNPs) are decorated in a layer-by-layer fashion with the oppositely charged aminocellulose (AM) and acylase to generate hybrid nanoentities with enhanced antibacterial and antibiofilm activities as well as reduced cytotoxicity. Acylase, a quorum-quenching enzyme that degrades the QS signals in the extracellular environment of bacteria, disrupts the bacterial QS process and together with the bactericidal AM synergistically lowers fourfold the minimum inhibitory concentration of the AgNPs templates toward Gram-negative Pseudomonas aeruginosa (P. aeruginosa). The hybrid nanoparticles in eightfold-lower concentration than the AgNPs inhibit 45% of the QS-regulated virulence factors produced by the reporter Chromobacterium violaceum bacterial strain and reduce by 100% the P. aeruginosa biofilm formation. Moreover, the sequential deposition of antibacterial/antibiofilm active and biocompatible biopolymers onto the AgNPs allows the engineering of safe nanomaterials that do not affect the viability of human cells.