Antimicrobial peptides: new candidates in the fight against bacterial infections

Antimicrobial peptides (AMPs) of innate origin are agents of the most ancient form of defense systems. They can be found in a wide variety of species ranging from bacteria through insects to humans. Through the course of evolution, host organisms developed arsenals of AMPs that protect them against a large variety of invading pathogens including both Gram-negative and Gram-positive bacteria. At a time of increasing bacterial resistance, AMPs have been the focus of investigation in a number of laboratories worldwide. Although recent studies show that some of the peptides are likely to have intracellular targets, the vast majority of AMPs appear to act by permeabilization of the bacterial cell membrane. Their activity and selectivity are governed by the physicochemical parameters of the peptide chains as well as the properties of the membrane system itself. In this review, we will summarize some of the recent developments that provide us with a better understanding of the mode of action of this unique family of antibacterial agents. Particular attention will be given to the determinants of AMP-lipid bilayer interactions as well as to the different pore formation mechanisms. The emphasis will be on linear AMPs but representatives of cysteine-bridged AMPs will also be discussed.