Identification of New Nitric Oxide-Donating Peptides with Dual Biofilm Eradication and Antibacterial Activities for Intervention of Device-Related Infections

Abstract

Implantable medical device-related infections with biofilms have become a significant challenge in clinic. Based on the potential bacteria biofilm dispersing effect of nitric oxide (NO) and the unique antibacterial activity of antimicrobial peptides (AMP), we synthesized five peptides and selected the most potent one to conjugate its N-terminal with a furoxan moiety to offer a hitherto-unknown NO-donating antimicrobial peptide (FOTyr-AMP), which exhibited S. aureus and E. coli biofilms dispersing and eradication, and potent antibacterial activities in vitro. In an implanted biofilms infection mice model, topical subcutaneous injection of FOTyr-AMP allowed synergetic eradication of bacterial biofilms and potent antibacterial activity, superior to antibiotic Cephalosporin C. Given low hemolysis effect, little influence on the blood pressure and potent in vivo efficacy of FOTyr-AMP, it is clear that subcutaneous administration of FOTyr-AMP could be a promising approach for the intervention of medical device-related biofilm infections with desirable safety.