Diversity of antimicrobial peptides and their mechanisms of action

Abstract

Antimicrobial peptides encompass a wide variety of structural motifs. Many peptides have α-helical structures. The majority of these peptides are cationic and amphipathic but there are also hydrophobic α-helical peptides which possess antimicrobial activity. In addition, some β-sheet peptides have antimicrobial activity and even antimicrobial α-helical peptides which have been modified to possess a β-structure retain part of their antimicrobial activity. There are also antimicrobial peptides which are rich in a certain specific amino acid such as Trp or His. In addition, antimicrobial peptides exist with thio-ether rings, which are lipopeptides or which have macrocyclic Cys knots. In spite of the structural diversity, a common feature of the cationic antimicrobial peptides is that they all have an amphipathic structure which allows them to bind to the membrane interface. Indeed, most antimicrobial peptides interact with membranes and may be cytotoxic as a result of disturbance of the bacterial inner or outer membranes. Alternatively, a necessary but not sufficient property of these peptides may be to be able to pass through the membrane to reach a target inside the cell. The interaction of these peptides with biological membranes is not just a function of the peptide but is also modulated by the lipid components of the membrane. It is not likely that this diverse group of peptides has a single mechanism of action, but interaction of the peptides with membranes is an important requirement for most, if not all, antimicrobial peptides.