title: Magainin 2-PGLa Interactions in Membranes - Two Peptides that Exhibit Synergistic Enhancement of Antimicrobial Activity.
abstract: The structural requirements for the synergistic enhancement of antimicrobial activities of the cationic linear peptides PGLa and magainin 2 were investigated. In a first step the antimicrobial activities were evaluated for a number of modifications of the sequences and equimolar mixtures thereof. In particular fluorophore labelled peptides maintain a high degree of antimicrobial activity and considerable synergism when tested conjointly. Thereafter, circular dichroism spectroscopy indicated that these extended sequences adopt helical conformations in the presence of model membranes similar to the unmodified sequences. Energy transfer between the fluorophores suggested that the peptides reside in close proximity to each other when bound to the membrane surface at high concentrations. The fluorophore interactions quickly diminish at lower peptide-to-lipid ratios indicating that the peptide-peptide interactions are weak. Furthermore, (15)N solid-state NMR measurements of the membrane topology of [(15)N-Ala14]-PGLa and of its fluorophorecarrying analogue reconstituted into supported 1, 2-didecanoyl-sn-glycero-3-phosphocholine bilayers were performed. These experiments revealed no correlation between the topological state of PGLa and the observed synergistic enhancement of antimicrobial activities due to the presence of magainins. These results suggest that lipid mediated interactions rather than the formation of tight peptide-peptide complexes in the membrane are responsible for synergistic activities of the mixtures.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Marquette
authors.forename: Evgeniy S
authors.initials: ES
authors.lastname: Salnikov
authors.forename: Elise
authors.initials: E
authors.lastname: Glattard
authors.forename: Christopher
authors.initials: C
authors.lastname: Aisenbrey
authors.affiliation: Universite de Strasbourg / CNRS, UMR7177, Institut de Chimie, 4, rue Blaise Pascal, 67070 Strasbourg, France. bechinge@unistra.fr.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Bechinger
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D004357:Drug Synergism; D004926:Escherichia coli / Q000187:drug effects*; D054806:Magainins / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D054806:Magainins; C045866:peptide-Gly-Leu-amide