Magainins as paradigm for the mode of action of pore forming polypeptides

Magainins are a class of antimicrobial Peptides discovered in the skin of Xenopus laevis. The Peptides kill bacteria by permeabilizing the cell membranes without exhibiting significant toxicity against mammalian cells, and are a promising candidate for a new Antibiotic of therapeutic value. The main target of the Peptides are considered to be the lipid matrix of the membranes. This review summarizes studies on magainin-lipid interactions in comparison with other pore forming Peptides. The selective toxicity can be at least partly explained by preferential interactions of magainins with anionic Phospholipids abundant in Bacterial membranes. A novel mode of action is discussed in detail, i.e., the formation of a dynamic peptide-lipid supramolecular pore, which allows the mutually coupled transbilayer transport of ions, lipids, and Peptides per se.