Oriented immobilization of Pep19-2.5 on antifouling brushes suppresses the development of Staphylococcus aureus biofilms

Abstract

Bacterial colonization of indwelling medical devices poses a danger to the patient and is a tremendous economic burden that costs billions of dollars to the healthcare system. Thus, it is essential to develop an effective mechanism that prevents the attachment of bacteria to the surface in combination with bactericidal strategies to kill them in direct contact. In this work, we combine the repellent/antifouling properties of polymer brushes with the antimicrobial activity of the synthetic peptide Pep19-2.5 and test its efficacy to inhibit Staphylococcus aureus biofilm formation. To tackle this, we utilized hierarchical polymer brushes, where the bottom block provides an effective barrier against adhesion while the top block provides functional groups for the immobilization of active molecules. Further, these polymer brushes were decorated with dibenzocyclooctine (DBCO)-functionalized Pep19-2.5 using strain-promoted alkyne-azide cycloaddition (SPAAC). This click chemistry proceeds very fast and does not require any catalyst, which is crucial for biomedical applications. The obtained coating was not only able to decrease the number of freely planktonic bacteria in the surrounding media (by 52.5%) but also inhibit the development of S. aureus biofilm by reducing the number of total, viable, and viable but non-culturable (VBNC) cells (up to 58%, 66%, and 70% respectively) and reduce the biovolume and thickness. Conversely, this coating does not exert any cytotoxic effect on Normal Human Dermal Fibroblasts (NHDF) cells. Thus, the combination of hierarchical polymer brushes with Pep19-2.5 is a promising approach to fight medical biofilms without affecting surrounding tissues.