Antimicrobial lipodepsipeptides from Pseudomonas spp: a comparison of their activity on model membranes

Lipodepsipeptides (LPDs) are a group of cyclic, acylated peptides produced by several Pseudomonas species. They are usually divided in two groups, mycins and peptins, on the basis of the size of the amino acidic part of the molecule. Mycins have a ring of 9 amino acids closed between the first and the last residue, peptins contain a more complex peptide moiety of up to 25 amino acids, partially cyclized. Both mycins and peptins attack the plasma membrane, but may have different target organisms. Comparing the mode of action of these two classes of LDPs on natural and model membranes we observed that all peptides induced red blood cell haemolysis and leakage of tonoplasts and liposornes by the formation of pores. The haemolytic activity of the smaller mycins was higher than that of the bigger peptins and proportional to the amphipathic index of the molecule. The extent of permeabilization was dependent also on the composition of the lipid membrane. In particular, mycins show a preference for sterols, whereas peptins are more active on phospholipids, especially sphingomyelin. These differences may have physiological implications. The formation of discrete ion channels, with anionic selectivity, was directly demonstrated by electrophysiological experiments performed on planar lipid bilayers or sugar beet vacuoles. The channels show sub-states and their properties in vacuoles and in planar lipid membranes were remarkably similar.