title: Bioactivity and the first transmission electron microscopy immunogold studies of short de novo-designed antimicrobial peptides.
abstract: In light of the era of microbial drug resistance, the current study aimed to better understand the relationships between sequence, higher-order structure, and mechanism of action for five designed peptides against multidrug-resistant (MDR) pathogens. All peptides studied were 15 residues long, were polycationic, adopted alpha-helical structures within hydrophobic environments (excluding the d-amino acid-substituted peptide MA-d), and contained N-terminal glycine residues, a novel antimicrobial peptide (AMP) design principle. Increasing hydrophobicity enhanced MICs (≤500 μg/ml to ≤7.4 μg/ml) without significantly increasing hemolytic activity (18% maximum hemolysis at 3,400 μg/ml). To the best of our knowledge, this is the first study to have successfully adapted and used a transmission electron microscopy (TEM) immunogold method to investigate the mechanism of action of short (∼15 residues long) AMPs within bacteria. We propose a "floodgate" mechanism to possibly explain membrane deformation and the relative absence of membrane-associated peptides 10 h into incubation.
authors.affiliation: Department of Biological Sciences, Faculty of Science, Thompson Rivers University, 900 McGill Road, Kamloops, BC V2C 5N3, Canada.
authors.forename: Marisa Ann
authors.initials: MA
authors.lastname: Azad
authors.forename: Heidi Esther Katrina
authors.initials: HE
authors.lastname: Huttunen-Hennelly
authors.forename: Cynthia
authors.initials: C
authors.lastname: Ross Friedman
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002942:Circular Dichroism; D007150:Immunohistochemistry / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D046529:Microscopy, Electron, Transmission / Q000379:methods*
chemical_list: D023181:Antimicrobial Cationic Peptides