Dermaseptins are an antimicrobial peptide family widely identified from the skin secretions of phyllomeudusinae frogs. Here, we identify Dermaseptin-PC (DM-PC), from the skin secretion of Phyllomedusa coelestis, and further investigate the properties of this peptide, and a number of rationally designed truncated derivatives. The truncated 19-mer derived from the N-terminus exhibited similar antimicrobial potency when compared to the parent peptide, but the haemolytic effect of this truncated peptide was significantly decreased. Based on previous studies, the charge and hydrophobicity of truncated derivatives can affect the bioactivity of these peptides and thus we designed a 10-mer derivative with an optimised positive charge and a cyclohexylalanine (Cha) at the C-terminus for enhancing the hydrophobicity, DMPC-10A, which retained the antimicrobial activity of the parent peptide. To further investigate the influence of Cha at the C-terminus on activity, it was substituted by alanine (Ala) to generate another derivative, DMPC-10, but this was found to be much less potent. In addition, DM-PC, DMPC-19 and DMPC-10A not only rapidly killed planktonic bacteria isolated from cystic fibrosis (CF) patient, but also effectively eradicated their biofilm matrices.
Keywords: antimicrobial peptide; cystic fibrosis infection; dermaseptin; peptide design.