Unexpected Bactericidal Activity of Poly(arginine)/Hyaluronan Nanolayered Coatings

Abstract

The number of nosocomial infections related to implants and medical devices increase alarmingly worldwide. New strategies based on the design of antimicrobial coatings are required to prevent such infections. Polyelectrolyte “multilayer” films constitute a powerful tool for nanoscale surface functionalization which allows addressing this issue. By investigating films built up with poly­(arginine) (PAR) of various chain lengths (10, 30, 100, and 200 residues) and hyaluronic acid (HA), we demonstrate that exclusively films constructed with poly­(arginine) composed of 30 residues (PAR30) acquire a strong antimicrobial activity against Gram-positive and Gram-negative pathogenic bacteria associated with infections of medical devices. This chain-size effect is extremely striking and is the first example reported where the length of the polyelectrolytes played a key-role in the functionality of the films. Moreover, this unexpected functionality of nanolayered polypeptide/polysaccharide PAR30/HA films occurs without adding any specific antimicrobial agent, such as antibiotics or antimicrobial peptides. PAR30/HA film inhibits bacteria through a contact-killing mechanism due to the presence of mobile PAR30 chains. These chains are assumed to diffuse toward the interface, where they interact with the bacteria with the consequence of killing them. This new coating with unique properties based on the association of a homopolypeptide of 30 residues with a polysaccharide constitutes a simple system to prevent implant-related infections with a reasonable production cost.

Antifungal Agents Based on Chitosan Oligomers, ε-polylysine and Streptomyces spp. Secondary Metabolites against Three Botryosphaeriaceae Species

“…It is worth noting that the fungicidal activity would likely benefit from the substitution of lysine with arginine residues, provided that previous works have demonstrated the superior cell permeability by arginine polymers over lysine-containing ones [33,34]. Mechanistic evidences indicate that arginine can enhance the activity of both translocating and membrane permeabilizing peptides [35,36].…”

Influence of poly‐l‐lysine molecular weight on antibacterial efficacy in polymer multilayer films

“…Mutschler et al found that the length of poly(arginine), a cationic polypeptide, in (poly(arginine)/HA) LbL films played a key role in the antibacterial effect of these films. Low‐MW poly(arginine) consisting of 30 repeat units was hypothesized to diffuse to the surface of the film and interact with surface exposed bacteria due to enhanced mobility compared to 100 and 200 repeat unit poly(arginine) films . Based on the intrinsic antibacterial properties of PLL and the findings of these previous studies, we hypothesized that PLL/HA assemblies may serve as antibacterial coatings that inhibit planktonic bacterial growth and bacterial surface attachment by a mechanism influenced by PLL mobility.…”

Effect of the Buffer on the Buildup and Stability of Tannic Acid/Collagen Multilayer Films Applied as Antibacterial Coatings

“…[11][12] The hydrophilicity 13 of the films, as well as their rigidity, 11,14 can be tuned by the adjustment of physico-chemical parameters of the film buildup, such as pH and/or ionic strength. Knowing that bacterial membranes are negatively charged, most of contact-killing LbL films were developed ending with positively charged polyelectrolytes [15][16][17][18] or quaternary ammonium containing polymers. [19][20] The bactericidal effect of these films is governed by the surface composition 13,16 or the diffusion of polycations in the films.…”

“…[19][20] The bactericidal effect of these films is governed by the surface composition 13,16 or the diffusion of polycations in the films. [17][18]21 Release-killing LbL films leach out antibacterial agents, by direct diffusion [22][23] or by film degradation due to hydrolysis, [24][25] pH 26 or enzymes. 27 Since a few decades, an intensive research is being carried out to explore the potential of polyphenols, found in plants as secondary metabolites, as antibacterial and antioxidants agents.…”