Characterizing a Detergent-Like Commonality Among Antimicrobial Peptides with Structural and Mechanistic Differences

Abstract

Largely distributed among living organisms, antimicrobial peptides are a class of small (<100 amino acid residues) host defense peptides that induce selective membrane lytic activity against microbial pathogens. The permeabilizing behavior of these diverse peptides has been commonly applied to the formation of pores, categorized as the barrel-stave, toroidal, or carpet type. With the continuing discovery of new peptide species, many are uncharacterized and the exact mechanism is unknown. Through the use of atomic force microscopy, we have previously shown that the disruption of mica supported lipid bilayer patches by protegrin-1, an 18-residue, cationic, beta sheet antimicrobial peptide isolated from pig leukocytes, is concentration dependent. The intercalation of antimicrobial peptide into the bilayer results in structures beyond that of pore formation including the observance of worm-like micelles. This suggests that antimicrobial peptide acts to lower the interfacial energy of the bilayer in a way similar to detergents. We pose that antimicrobial peptides act universally within a detergent-like mechanism in which pore formation is a small part of a much more complex phase diagram that spans peptide-lipid aggregates beyond that of lamellar bilayers. Antimicrobial peptides with structural and mechanistic differences have been studied and current results with magainin-1 and aurein 1.1 for example exhibit a mechanistic commonality. Future aspirations of antimicrobial peptides as new sources of antibiotics may be realized as a universal mechanism can streamline the synthesis of de novo designed peptides.