Staphylococcus aureus selective antimicrobial polymers based on an arginine-derived monomer

Abstract

The continuous spread of resistance genes among bacterial populations, in particular in hospital setting, threatens the advances of our medical systems and already costs more than 1 million lives per year. Antimicrobial polymers (APs) are a promising type of materials to counteract these developments, as they are non-susceptible toward resistance development, and even target resistant bacteria. We herein show the synthesis of an arginine-containing monomer and its polymerization via photo-induced reversible addition-fragmentation chain-transfer polymerization. The synthesis is straightforward, and the macromolecules possess two charged functions (i.e., guanidinium and ammonium) per repeating unit after deprotection. Assessment of the biological activity reveals that polymers inhibit the growth of methicillin-resistant Staphylococcus aureus (MRSA) while being relatively inactive against tested Gram-negative strains. Surprisingly, among the tested polymers, the homopolymer of the arginine-derived monomer is the best-performing material, even though it possesses no notable hydrophobic units. Toxicity tests against red blood cells and other mammalian cells show a good biocompatibility of polymers, leading to an overall excellent selectivity. Using membrane models, the mechanism of action was found to be membrane disruption. The good selectivity of the herein presented polymer for MRSA makes them promising materials for the development of therapeutic agents against such infections.