Host Defense Peptide-Mimicking Amphiphilic β-Peptide Polymer (Bu:DM) Exhibiting Anti-Biofilm, Immunomodulatory, and <i>in Vivo</i> Anti-Infective Activity
Hashem Etayash, Yuxin Qian, Daniel Pletzer, Qiang Zhang, Jiayang Xie, Ruxin Cui, Chengzhi Dai, Pengcheng Ma, Qi Fan, Runhui Liu, Robert E. W. Hancock
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.