Fusions of a carbohydrate binding module with the small cationic hexapeptide RWRWRW confer antimicrobial properties to cellulose-based materials

Abstract

The emergence of antibiotic-resistant bacteria is a critical worldwide healthcare problem. In the specific case of wound care, new and effective alternatives to currently available solutions are urgently needed. Cellulose-based dressings, for example, could be made more attractive if rendered antimicrobial. This work proposes a new strategy to modify cellulose-based materials with the short antimicrobial hexapeptide MP196 (RWRWRW-NH₂) that relies on a biomolecular recognition approach based on carbohydrate binding modules (CBMs). Specifically, we focused on the modification of hydrogels, paper, and microfibrillated cellulose (MFC) with fusions of the CBM3 from Clostridium thermocellum (C. thermocellum) with derivatives of MP196. The fusions are prepared by promoting the formation of a disulfide bond between Cys-terminated derivatives of MP196 and a CBM3 that is pre-anchored in the materials. The CBM3-MP196-modified materials displayed antibacterial activity against Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus) that was significantly higher when compared with the activity of materials prepared by physical adsorption of MP196. The biomolecular strategy provides a more favorable orientation, exposure, and distancing of the peptide from the matrix. This versatile concept provides a toolbox for the functionalization of cellulose materials of different origins and architectures with a broad choice in peptides. Functionalization under mild biological conditions avoids further purification steps, allowing for translational research and multiple applications as drug delivery systems, scaffolds for tissue engineering and biomaterials. STATEMENT OF SIGNIFICANCE: The emergence of antibiotic-resistant bacteria is a critical worldwide healthcare problem. In the specific case of wound care, new and effective alternatives to currently available solutions are urgently needed. This work proposes a new strategy to modify cellulose-based materials with a short antimicrobial hexapeptide that relies on a biomolecular recognition approach based on carbohydrate binding modules. The modified materials displayed antibacterial activity against both Gram-negative and Gram-positive bacteria. The biomolecular strategy provides a favorable orientation, exposure, and distancing of the peptide from the matrix. This versatile concept offers a toolbox for the functionalization of different cellulose materials with a broad choice in peptides. Functionalization under mild biological conditions avoids further purification steps, allowing for translational research and multiple applications.

Keywords: Antibacterial; Biomaterial; Biomolecular recognition; Carbohydrate‐binding modules; Cellulose.