title: Interactions of a class IIb bacteriocin with a model lipid bilayer, investigated through molecular dynamics simulations.
abstract: The emergence of antibiotic resistant microorganisms poses an alarming threat to global health. Antimicrobial peptides (AMPs) are considered a possible effective alternative to conventional antibiotic therapies. An understanding of the mechanism of action of AMPs is needed in order to better control and optimize their bactericidal activity. Plantaricin EF is a heterodimeric AMP, consisting of two peptides Plantaricin E (PlnE) and Plantaricin F (PlnF). We studied the behavior of these peptides on the surface of a model lipid bilayer. We identified the residues that facilitate peptide-peptide interactions. We also identified residues that mediate interactions of the dimer with the membrane. PlnE interacts with the membrane through amino acids at both its termini, while only the N terminus of PlnF approaches the membrane. By comparing the activity of single-site mutants of the two-peptide bacteriocin and the simulations of the bacteriocin on the surface of a model lipid bilayer, structure activity relationships are proposed. These studies allow us to generate hypotheses that relate biophysical interactions observed in simulations with the experimentally measured activity. We find that single-site amino acid substitutions result in markedly stronger antimicrobial activity when they strengthen the interactions between the two peptides, while, concomitantly, they weaken peptide-membrane association. This effect is more pronounced in the case of the PlnE mutant (G20A), which interacts the strongest with PlnF and the weakest with the membrane while displaying the highest activity.
authors.affiliation: Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN 55455, United States.
authors.forename: Panagiota K
authors.initials: PK
authors.lastname: Kyriakou
authors.affiliation: Department of Biosciences, University of Oslo, Post box 1041 Blindern, 0316 Oslo, Norway.
authors.forename: Bie
authors.initials: B
authors.lastname: Ekblad
authors.affiliation: Department of Biosciences, University of Oslo, Post box 1041 Blindern, 0316 Oslo, Norway.
authors.forename: Per Eugen
authors.initials: PE
authors.lastname: Kristiansen
authors.affiliation: Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN 55455, United States. Electronic address: yiannis@umn.edu.
authors.forename: Yiannis N
authors.initials: YN
authors.lastname: Kaznessis
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000737:chemistry; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000494:pharmacology; D001430:Bacteriocins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D002462:Cell Membrane / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D056004:Molecular Dynamics Simulation
chemical_list: D000596:Amino Acids; D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D001430:Bacteriocins; D008051:Lipid Bilayers; C117244:plantaricin EF
keywords: Antibiotic resistance; Antimicrobial peptides; Bacteriocins