[Bacteria-selective synergism between the antimicrobial peptides magainin 2 and tachyplesin I: toward cocktail therapy].
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.
Kobayashi
Satoe
S
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D004357:Drug Synergism; D004926:Escherichia coli / Q000166:cytology / Q000187:drug effects; D054806:Magainins; D008563:Membrane Lipids; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology*; D010743:Phospholipids; D017433:Protein Structure, Secondary; D013212:Staphylococcus epidermidis / Q000166:cytology / Q000187:drug effects; D029867:Xenopus Proteins
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D004268:DNA-Binding Proteins; D054806:Magainins; D008563:Membrane Lipids; D010456:Peptides, Cyclic; D010743:Phospholipids; D029867:Xenopus Proteins; C053301:magainin 2 peptide, Xenopus; C057636:tachyplesin peptide, Tachypleus tridentatus