Imidazolium-Based Polypeptide Coating with a Synergistic Antibacterial Effect and a Biofilm-Responsive Property

Surface modification with cationic polymer coatings represented an important strategy to address the medical device-related infection issues. However, limited antibacterial activities and high cytotoxicity have hampered their development. Herein, we report a facile method to enhance the surface antibacterial activity by construction of an imidazolium-based polypeptide with fosfomycin counteranions (i.e., S₄-PIL-FS). The polypeptide coating displayed a synergistic antibacterial effect from the combination of membrane disruption and inhibition of initial cell wall synthesis, leading to higher in vitro and in vivo surface antibacterial activities than cationic polypeptide or fosfomycin sodium alone. S₄-PIL-FS also showed a decrease in the hemolytic ratio and cytotoxicity toward different mammalian cells. Moreover, we observed an interesting biofilm-responsive property of S₄-PIL-FS originating from the esterase-induced cleavages of side-chain ester bonds that enabled an antibiofilm property of the cationic polypeptide coating.