Insect-derived hybrid antimicrobial peptides: antibiotics for the next generation?

There has been recent interest in utilizing natural antimicrobial peptides (AMPs) as novel antibiotics. Hybrid antimicrobial peptides (hAMPs) are synthetic molecules containing active motifs from multiple parental AMPs. This thesis presents in vitro activity data of hAMPs designed b y combining binding and killing motifs from different invertebrate and vertebrate AMPs. The goals of hAMP design are to improve antimicrobial efficacy and reduce host cytotoxicity. Activity was further optimized by modifying basic properties of the peptide such as charge, hydrophobicity, peptide length and specific amino acid composition. Overall, hAMPs exhibited higher antimicrobial efficacy than their active motifs alone in vitro. Some hAMPs kill bacteria through membrane permeabilization while others likely attack intracellular targets. Synergistic activity was observed when different hAMPs were combined together separately or when combined in the form of a multivalent hAMP. Our results indicate that hAMPs may be suitable for use as novel antimicrobial agents.