title: Investigations of the synergistic enhancement of antimicrobial activity in mixtures of magainin 2 and PGLa.
abstract: Magainins are antimicrobial peptides isolated from the African clawed frog Xenopus laevis. They interact with bacterial membranes where they cause channel formation and membrane disruption. When added as a cocktail magainin 2 and PGLa are considerably more efficient when compared to the corresponding amounts of individual components. In order to investigate this synergistic interaction of PGLa and magainin a number of magainin variants have been prepared and investigated in biological and biophysical assays. In particular we report on the antimicrobial activities and solid-state NMR investigations of magainins that have been extended by a carboxyterminal GGC tripeptide to form covalently linked dimers. Notably, when the formation of the covalent linkage is prevented by exchanging the cystein by serine or alanine no loss in efficiency was observed indicating that the covalent interaction is not necessary for synergistic interaction. In a next step peptides labelled with (15)N and (2)H were reconstituted into oriented membranes and their topology studied by solid-state NMR spectroscopy. The tendency of some of these peptides to adopt membrane-spanning alignments does not correlate with their synergistic activities in antimicrobial assays. In contrast, the stable alignment of PGLa parallel to the surface of membranes made of Escherichia coli lipid extracts is strongly suggestive that the peptides develop synergistic activities when in an in-planar configuration. Notably, the phospholipid head groups of these samples show a high degree of disturbance suggesting that the synergistic interactions between the magainin peptides could be mediated through the lipid phase.
authors.affiliation: Université de Strasbourg, CNRS, UMR7177, Institut de Chimie, 4, Rue Blaise Pascal, 67070 Strasbourg, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Glattard
authors.affiliation: Université de Strasbourg, CNRS, UMR7177, Institut de Chimie, 4, Rue Blaise Pascal, 67070 Strasbourg, France.
authors.forename: Evgeniy S
authors.initials: ES
authors.lastname: Salnikov
authors.affiliation: Université de Strasbourg, CNRS, UMR7177, Institut de Chimie, 4, Rue Blaise Pascal, 67070 Strasbourg, France.
authors.forename: Christopher
authors.initials: C
authors.lastname: Aisenbrey
authors.affiliation: Université de Strasbourg, CNRS, UMR7177, Institut de Chimie, 4, Rue Blaise Pascal, 67070 Strasbourg, France. Electronic address: bechinger@unistra.fr.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Bechinger
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects; D054806:Magainins / Q000737:chemistry* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D054806:Magainins; C045866:peptide-Gly-Leu-amide
keywords: Amphipathic helix; Antimicrobial activities; Membrane topology; Peptide–lipid interactions; Solid-state NMR; Supported lipid bilayer