Mode of action of linear amphipathic alpha-helical antimicrobial peptides

The increasing resistance of bacteria to conventional antibiotics resulted in a strong effort to develop antimicrobial compounds with new mechanisms o f action. Antimicrobial peptides seem to be a promising solution to this pr oblem. Many studies aimed at understanding their mode of action were descri bed in the past few years. The most studied group includes the linear, most ly ct-helical peptides. Although the exact mechanism by which they kill bac teria is not clearly understood, it has been shown that peptide-lipid inter actions leading to membrane permeation play a role in their activity. Membr ane permeation by amphipathic ct-helical peptides can proceed via either on e of the Two mechanisms: (a) transmembrane pore formation via a "barrel-sta ve" mechanism; and bi membrane destruction/solubilization via a "carpet-lik e" mechanism. The purpose of this review is to summarize recent studies aim ed at understanding the mode of action of linear a-helical antimicrobial pe ptides. This review which is focused on magainins, cecropins, and dermasept ins as representatives of the amphipathic a-helical antimicrobial peptides, supports the carpet-like rather the barrel-stave mechanism. That these pep tides vary with regard to their length, amino acid composition, and net pos itive charge, but act via a common mechanism, may imply that other linear a ntimicrobial peptides that share the same properties also share the same me chanism (C) 1999 John Wiley & Sons, Inc.