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 antimicrobial peptides discovered from 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 exhibited marked synergistic effects against Gram-negative and Gram-positive bacteria without enhancing hemolytic activity as a measure of toxicity. 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 suggested the possibility of the development of cocktail therapeutic regimens using combinations of antimicrobial peptides.
Kobayashi
S
S
Graduate Schools of Pharmaceutical Sciences and Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Hirakura
Y
Y
Matsuzaki
K
K
D000328:Adult; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D001665:Binding Sites; D002462:Cell Membrane / Q000502:physiology; D002942:Circular Dichroism; D004268:DNA-Binding Proteins / Q000494:pharmacology*; D004357:Drug Synergism; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D005452:Fluoresceins / Q000378:metabolism; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000254:growth & development; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000254:growth & development; D006461:Hemolysis / Q000187:drug effects; D006737:Horseshoe Crabs; D006801:Humans; D054806:Magainins; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism; D011487:Protein Conformation; D012867:Skin / Q000378:metabolism; D029867:Xenopus Proteins; D014982:Xenopus laevis
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D004268:DNA-Binding Proteins; D005452:Fluoresceins; D054806:Magainins; D010456:Peptides, Cyclic; D010743:Phospholipids; D029867:Xenopus Proteins; C053301:magainin 2 peptide, Xenopus; C057636:tachyplesin peptide, Tachypleus tridentatus; C007740:fluorexon