title: Membrane interactions and biological activity of antimicrobial peptides from Australian scorpion.
abstract: UyCT peptides are antimicrobial peptides isolated from the venom of the Australian scorpion. The activity of the UyCT peptides against Gram positive and Gram negative bacteria and red blood cells was determined. The membrane interactions of these peptides were evaluated by dye release (DR) of the fluorophore calcein from liposomes and isothermal titration calorimetry (ITC); and their secondary structure was determined by circular dichroism (CD). Three different lipid systems were used to mimic red blood cells, Escherichia coli and Staphylococcus aureus membranes. UyCT peptides exhibited broad spectrum antimicrobial activity with low MIC for S. aureus and multi-drug resistant Gram negative strains. Peptide combinations showed some synergy enhancing their potency but not hemolytic activity. The UyCT peptides adopted a helical structure in lipid environments and DR results confirmed that the mechanism of action is by disrupting the membrane. ITC data indicated that UyCT peptides preferred prokaryotic rather than eukaryotic membranes. The overall results suggest that UyCT peptides could be pharmaceutical leads for the treatment of Gram negative multiresistant bacterial infections, especially against Acinetobacter baumanni, and candidates for peptidomimetics to enhance their potency and minimize hemolysis. This article is part of a Special Issue entitled: Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and Kalina Hristova.
authors.affiliation: Australian Venom Research Unit, Department of Pharmacology, University of Melbourne, Victoria 3010, Australia; Cardiovascular Therapeutics Unit, Department of Pharmacology, University of Melbourne, Victoria 3010, Australia.
authors.forename: Karen
authors.initials: K
authors.lastname: Luna-Ramírez
authors.affiliation: School of Chemistry, Bio21 Institute, University of Melbourne, Melbourne, VIC 3010, Australia.
authors.forename: Marc-Antoine
authors.initials: MA
authors.lastname: Sani
authors.affiliation: Instituto Nacional de Salud Pública, Centro de Investigación sobre Enfermedades Infecciosas, Avenida Universidad 655, Cuernavaca, Morelos 62508, Mexico.
authors.forename: Jesus
authors.initials: J
authors.lastname: Silva-Sanchez
authors.affiliation: Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Avenida Universidad, 2001, Colonia Chamilpa, Apartado Postal 510-3, Cuernavaca 62210, Mexico.
authors.forename: Juana María
authors.initials: JM
authors.lastname: Jiménez-Vargas
authors.affiliation: Instituto Nacional de Salud Pública, Centro de Investigación sobre Enfermedades Infecciosas, Avenida Universidad 655, Cuernavaca, Morelos 62508, Mexico.
authors.forename: Fernando
authors.initials: F
authors.lastname: Reyna-Flores
authors.affiliation: Australian Venom Research Unit, Department of Pharmacology, University of Melbourne, Victoria 3010, Australia.
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Winkel
authors.affiliation: Australian Venom Research Unit, Department of Pharmacology, University of Melbourne, Victoria 3010, Australia; Cardiovascular Therapeutics Unit, Department of Pharmacology, University of Melbourne, Victoria 3010, Australia.
authors.forename: Christine E
authors.initials: CE
authors.lastname: Wright
authors.affiliation: Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Avenida Universidad, 2001, Colonia Chamilpa, Apartado Postal 510-3, Cuernavaca 62210, Mexico. Electronic address: possani@ibt.unam.mx.
authors.forename: Lourival D
authors.initials: LD
authors.lastname: Possani
authors.affiliation: School of Chemistry, Bio21 Institute, University of Melbourne, Melbourne, VIC 3010, Australia. Electronic address: fs@unimelb.edu.au.
authors.forename: Frances
authors.initials: F
authors.lastname: Separovic
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects*; D002942:Circular Dichroism; D004926:Escherichia coli / Q000187:drug effects; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D017433:Protein Structure, Secondary; D012605:Scorpions / Q000737:chemistry; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; D008081:Liposomes; D010455:Peptides
keywords: Antibiotic; Antimicrobial peptide; Dye release; Hemolysis; Membrane interaction; Phospholipid