Interaction of hagfish cathelicidin antimicrobial peptides with model lipid membranes.
Hagfish intestinal antimicrobial peptides (HFIAPs) are a family of polycationic peptides exhibiting potent, broad-spectrum bactericidal activity. In an attempt to unravel the mechanism of action of HFIAPs, we have studied their interaction with model membranes. Synthetic HFIAPs selectively bound to liposomes mimicking bacterial membranes, and caused the release of vesicle-encapsulated fluorescent markers in a size-dependent manner. In planar lipid bilayer membranes, HFIAPs induced erratic current fluctuations and reduced membrane line tension according to a general theory for lipidic pores, suggesting that HFIAP pores contain lipid molecules. Consistent with this notion, lipid transbilayer redistribution accompanied HFIAP pore formation, and membrane monolayer curvature regulated HFIAP pore formation. Based on these studies, we propose that HFIAPs kill target cells, at least in part, by interacting with their plasma membrane to induce formation of lipid-containing pores. Such a membrane-permeabilizing function appears to be an evolutionarily conserved host-defense mechanism of antimicrobial peptides.
Basañez
Gorka
G
Unidad de Biofísica (Centro Mixto UPV/CSIC), y Departamento de Bioquímica y Biología Molecular, Universidad del Pais Vasco (UPV/EHU), P.O. Box 644, 48080 Bilbao, Spain. gbzbaasg@lg.ehu.es
Shinnar
Ann E
AE
Zimmerberg
Joshua
J
D000818:Animals; D000890:Anti-Infective Agents / Q000378:metabolism / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism / Q000494:pharmacology*; D054804:Cathelicidins; D002463:Cell Membrane Permeability / Q000187:drug effects; D004553:Electric Conductivity; D006196:Hagfishes / Q000276:immunology; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008081:Liposomes / Q000378:metabolism; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism*
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D008051:Lipid Bilayers; D008081:Liposomes; D008563:Membrane Lipids