We developed an antimicrobial peptide (AMP) as a candidate substance for replacing antibiotics. Previously, a novel 18-amino acid antimicrobial peptide Hylin a1 was isolated from an electro-stimulated arboreal South American frog Hypsiboas albopunctatus, and was found to demonstrate antimicrobial activity and cytotoxicity. In a recent study, the analog peptides were designed based on the parent peptide Hylin a1 to decrease toxicity and to maintain antimicrobial efficacy. The analog peptides were substituted with alanine and lysine, resulting in the formation of amphipathic α-helical structures in membrane-mimicking environments and in the induction of hydrophobic moments and net charges. Moreover, the analog peptides showed lower hemolytic effects and mammalian cell selectivity than Hylin a1. In particularly Hylin a1-11K and Hylin a1-15K exhibited broad-spectrum antimicrobial activity and anti-biofilm activity against carbapenem-resistant Acinetobacter baumannii. Permeability assays indicated that analog peptides eliminated bacteria by binding to lipopolysaccharide and by disrupting the bacterial membrane. Hylin a1-11K and Hylin a1-15K reduced inflammation by suppressing pro-inflammatory cytokines expression by A. baumannii infection and effectively ameliorated carbapenem-resistant A. baumannii infection in mice. Thus, analog peptides substituted with several residues based on Hylin a1 may be effective for treating carbapenem-resistant A. baumannii infections.

*This paper was published at European Journal of Pharmaceutical Sciences, Volume 175, August 2022, Pages 106205.