Host Defense Peptide-Mimicking Amphiphilic β-Peptide Polymer (Bu:DM) Exhibiting Anti-Biofilm, Immunomodulatory, and in Vivo Anti-Infective Activity

Abstract

Therapeutic options to treat multidrug resistant bacteria, especially when present in biofilms, are limited due to their high levels of antibiotic resistance. Here, we report the anti-biofilm and immunomodulatory activities of the host defense peptide (HDP)-mimicking β-peptide polymer (20:80 Bu:DM) and investigated its activity in vivo. The polymer outperformed antibiotics in the removal and reduction of the viability of established biofilms, achieving a maximum activity of around 80% reduction in viability. Interestingly the polymer also exhibited HDP-like immunomodulation in inducing chemokines and anti-inflammatory cytokines and suppressing lipopolysaccharide-induced proinflammatory cytokines. When tested in a murine, high-density skin infection model using P. aeruginosa LESB58, the polymer was effective in diminishing abscess size and reducing bacterial load. This study demonstrates the dual functionality of HDP-mimicking β-peptide polymers in inhibiting biofilms and modulating innate immunity, as well as reducing tissue dermonecrosis.