Bacteria-selective synergism between the antimicrobial peptides alpha-helical magainin 2 and cyclic beta-sheet tachyplesin I: Toward cocktail therapy

Magainin 2 and tachyplesin I (T-SS) are membrane-permeabilizing antimicrobi al peptides discovered from frog skin and horseshoe crab hemolymph, respect ively. They are classified into different secondary structural classes. i.e .. a-helix and cyclic beta -sheet, respectively. We found that F5W-magainin 2 (MG2) and T-SS exhibited marked synergistic effects against Gram-negativ e and Grain-positive bacteria without enhancing hemolytic activity as a mea sure of toxicity. Dye release experiments using liposomes suggested that th e selective synergism is mainly due to anionic phospholipid-specific synerg ism 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 suggested th e possibility of the development of cocktail therapeutic regimens using com binations of antimicrobial peptides.