[Bacteria-selective synergism between the antimicrobial peptides magainin 2 and tachyplesin I: toward cocktail...

Magainin 2 and tachyplesin I (T-SS) are membrane-permeabilizing antimicrobial peptides discovered in frog skin and horseshoe crab hemolymph, respectively. They are classified into different secondary structural classes, i.e., alpha-helix and cyclic beta-sheet, respectively. We found that F5W-magainin 2 (MG2) and T-SS showed marked synergistic effects against gram-negative and-positive bacteria without enhancing hemolytic activity as a measure of toxicity. The results of dye-release experiments using liposomes suggested that the selective synergism is mainly due to anionic phospholipid-specific synergism in membrane permeabilization. Furthermore, the cyclic structure of T-SS was found to be necessary for synergism because a linear analogue of T-SS did not show good synergism with MG2. These novel observations suggest the possibility of development of cocktail therapeutic regimens using combinations of antimicrobial peptides.