Nanosilver Mitigates Biofilm Formation via FapC Amyloidosis Inhibition

Abstract

Multidrug resistance of bacteria is a major challenge due to the wide‐spread use of antibiotics. While a range of strategies have been developed in recent years, suppression of bacterial activity and virulence via their network of extracellular amyloid has rarely been explored, especially with nanomaterials. Here, silver nanoparticles and nanoclusters (AgNPs and AgNCs) capped with cationic branched polyethylenimine polymer are synthesized, and their antimicrobial potentials are determined at concentrations safe to mammalian cells. Compared with the ultrasmall AgNCs, AgNPs entail stronger binding to suppress the fibrillization of FapC, a major protein constituent of the extracellular amyloid matrix of Pseudomonas aeruginosa. Both types of nanoparticles exhibit concentration‐dependent antibiofilm and antimicrobial properties against P. aeruginosa. At concentrations of 1 × 10−6 m or below, both the bactericidal activity of AgNCs and the antibiofilm capacity of AgNPs are associated with their structure‐mediated bio–nano interactions but not ion release. For AgNPs, specifically, their antibiofilm potency correlates with their capacity of FapC fibrillization inhibition, but not with their bactericidal activity. This study demonstrates the antimicrobial potential of safe nanotechnology through the novel route of amyloidosis inhibition.

Selective antibiofilm properties and biocompatibility of nano-ZnO and nano-ZnO/Ag coated surfaces

“…Although metal effect to surface associated amyloids (SAFs) in biofilm matrix is yet scarcely studied 44,45 , we also hypothesized that high Zn concentrations might interfere with bacterial surface-associated amyloid [71][72][73][74] formation as it can negatively affect fibrillar structure of other amyloids [75][76][77][78][79] and could thereby disrupt SAF-mediated surface colonization. Although cell surface morphology seemed to differ between E. coli cells grown on nano-ZnO and uncoated surfaces in oligotrophic conditions (Fig.…”

Interactions of Gold and Silver Nanoparticles with Bacterial Biofilms: Molecular Interactions behind Inhibition and Resistance

“…Hence, proteins are one of the attractive targets for finding new antimicrobial therapies. To date, it has been shown that AuNPs and AgNPs, along with their respective ions, interact with several structural proteins, membrane proteins and several enzymes [ 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ]. In an experimental and molecular docking study, Shah et al evidenced the diverse action of AgNPs on various proteins of Pseudomonas aeruginosa [ 32 ].…”

“…In this study, it is reported that several amino acids—leucine, aspartate, arginine, lysine, tyrosine, arginine, alanine and tryptophan—from active sites of the four proteins interact with AgNPs [ 33 ]. Structural proteins, such as bacterial amyloid FapC in P. aeruginosa , form a branched structure that helps in cell–cell adhesion, encasing dormant cells, QS, protection and biofilm integrity [ 34 ]. In a study done by Huma et al, AgNPs prevented fibrilization of FapC proteins by interacting with and sequestering FapC monomers ( Figure 3 B).…”

“…In a study done by Huma et al, AgNPs prevented fibrilization of FapC proteins by interacting with and sequestering FapC monomers ( Figure 3 B). To support these experimental findings, when the authors performed an in silico analysis, they found that AgNPs interacted via electrostatic, hydrophobic and hydrogen-bonding interactions with several amino acid residues of the FapC protein [ 34 ]. In vitro thermodynamic study on branched polyethylenimine coated silver nanoparticles (bPEI-AgNPs) also supported the existence of electrostatic, hydrophobic and hydrogen-bonding interactions as well as changes in the secondary structure of alpha lactalbumin protein due to these interactions [ 35 ].…”

A smart hydrogel for on-demand delivery of antibiotics and efficient eradication of biofilms

“…Nanomedicines and biomaterials have shown great promise in the treatment of various diseases in recent years [17][18][19][20]. To treat biofilm-associated infections, quorum sensing inhibitors [21,22], nanoparticles [23][24][25], antimicrobial peptides [26], antisense nucleic acids [27,28], enzyme mimetics [29], polymers [30][31][32] and antifouling coatings [33][34][35][36] with the activity of inhibiting biofilm formation were developed in the past decade. These compounds or materials could sensitize biofilm infections to conventional antibiotics [6,37].…”