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

Abstract

Many bacteria have the capability to form a three-dimensional, strongly adherent network called 'biofilm'. Biofilms provide adherence, resourcing nutrients and offer protection to bacterial cells. They are involved in pathogenesis, disease progression and resistance to almost all classical antibiotics. The need for new antimicrobial therapies has led to exploring applications of gold and silver nanoparticles against bacterial biofilms. These nanoparticles and their respective ions exert antimicrobial action by damaging the biofilm structure, biofilm components and hampering bacterial metabolism via various mechanisms. While exerting the antimicrobial activity, these nanoparticles approach the biofilm, penetrate it, migrate internally and interact with key components of biofilm such as polysaccharides, proteins, nucleic acids and lipids via electrostatic, hydrophobic, hydrogen-bonding, Van der Waals and ionic interactions. Few bacterial biofilms also show resistance to these nanoparticles through similar interactions. The nature of these interactions and overall antimicrobial effect depend on the physicochemical properties of biofilm and nanoparticles. Hence, study of these interactions and participating molecular players is of prime importance, with which one can modulate properties of nanoparticles to get maximal antibacterial effects against a wide spectrum of bacterial pathogens. This article provides a comprehensive review of research specifically directed to understand the molecular interactions of gold and silver nanoparticles with various bacterial biofilms.

Keywords: antimicrobials; biofilm; biofilm inhibition; gold nanoparticles (AuNPs); molecular interactions; silver nanoparticles (AgNPs).

Figure 1

(A) The process of biofilm formation in which the bacterial cells approach a biological or non-biological surface (1), adhere firmly (2), multiply (3) and secret extracellular polymeric substances (4). Eventually, this whole mass (i.e., biofilm) grows (5 and 6) into a 3D complex structure that contains nucleic acids, polysaccharides, lipids, proteins, ions and water (magnified circle). (B) The mechanism of antibacterial action of gold nanoparticles, silver nanoparticles, and their respective ions, which act on seven specific targets in bacterial cells. The sizes of molecules and bacteria are not to scale, and they are represented arbitrarily for schematic representation only.

Figure 2

Schematic representation of interactions between biofilm nucleic acids and gold or silver nanoparticles. (A) Cationic gold nanoparticles, silver nanoparticles and their respective metal ions show electrostatic interactions, hydrophobic interactions and Van der Waals interactions with polyanionic eDNA in the biofilm. (B) The metal ions (Au⁺ and Ag⁺) in particular show affinity towards G-C base pairs of eDNA, where they preferentially interact with oxygen and nitrogen atoms via short-range Van der Waals forces and hydrophobic forces. (C) In order to withstand oxidative damage, bacteria undergo phosphorothioation modification of DNA. Gold nanoparticles show highly specific gold–sulphur (Au-S) bonding interactions with such eDNA. (D) Both gold and silver nanoparticles and their ions show electrostatic interactions and Van der Waals interactions with bacterial RNA and tRNA. Red arrows in the figure indicate different types of interactions.

Figure 3

Schematic representation of various interactions between gold or silver nanoparticles and biofilm proteins. (A) The metallic nanoparticles (e.g., silver nanoparticles) interact with few proteins that are involved in quorum sensing (e.g., LasR) via electrostatic, hydrophobic and hydrogen-bonding interactions. In this case, nanoparticles and their ions preferentially interact with amino acids at ligand binding sites, making them inactive for cell signaling. (B) Gold and silver nanoparticles also interact via electrostatic, hydrophobic and hydrogen-bonding interactions with amyloid-forming proteins such as FapC, sequester its monomers and create defects in bacterial cell structure. (C) Several metabolic proteins and enzymes in the biofilm interact with nanoparticles via electrostatic, hydrophobic, hydrogen-bonding, Van der Waals and π–π interactions, causing collapse in the protein structure and eventually making them inactive for metabolism. (D) Gold nanoparticles and gold ions show strong Au-S bonding interactions while interacting with thiol-containing proteins of the biofilms. (E) Gold and silver nanoparticles also interact with functional oligomers of certain proteins via electrostatic and hydrophobic interactions and lead to their association or dissociation, which ultimately leads to impairment in their function in the biofilm. (F) Membrane proteins (e.g., electron transport system) also have similar interactions with metal ions and metallic nanoparticles that leads to loss in integrity and changes in membrane protein functions. Red arrows in the figure indicate all types of interactions.

Figure 4

Schematic representation of interactions between gold or silver nanoparticles and polysaccharides of biofilm. (A) Bacterial polysaccharides (LPS, teichoic acid and lipoteichoic acid) show electrostatic interactions, hydrogen-bonding interactions and hydrophobic interactions with cationic gold and silver nanoparticles. Neutral and anionic gold and silver nanoparticles show no or minimal interactions under the same experimental conditions. (B) In some cases, the nanoparticles stabilized with large, non-ionic polymers (e.g., PVP coated AgNPs) show specific electrosteric repulsive interactions with biofilm polysaccharides. (C) Antimicrobial peptide coated gold and silver nanoparticles show electrostatic as well as hydrophobic interactions with biofilm polysaccharides (e.g., alginate in P. aeruginosa biofilm). Red arrows in the figure indicate all types of interactions.

Figure 5

Schematic representation of interactions between biofilm lipids and gold or silver nanoparticles. (A) Cationic gold nanorods, gold nanoparticles and silver nanoparticles along with their respective ions interact with biofilm lipid and lipopolysaccharides via electrostatic and hydrophobic interactions. Whereas, anionic or neutral nanoparticles or nanorods show minimal or no interactions at all. (B) Gold nanorods, gold nanoparticles and silver nanoparticles coated with lipid moiety or any other hydrophobic moiety preferentially show hydrophobic interactions with biofilm lipids. Red arrows in the figure indicate different types of interactions.