title: Membrane Core-Specific Antimicrobial Action of Cathelicidin LL-37 Peptide Switches Between Pore and Nanofibre Formation.
abstract: Membrane-disrupting antimicrobial peptides provide broad-spectrum defence against localized bacterial invasion in a range of hosts including humans. The most generally held consensus is that targeting to pathogens is based on interactions with the head groups of membrane lipids. Here we show that the action of LL-37, a human antimicrobial peptide switches the mode of action based on the structure of the alkyl chains, and not the head groups of the membrane forming lipids. We demonstrate that LL-37 exhibits two distinct interaction pathways: pore formation in bilayers of unsaturated phospholipids and membrane modulation with saturated phospholipids. Uniquely, the membrane modulation yields helical-rich fibrous peptide-lipid superstructures. Our results point at alternative design strategies for peptide antimicrobials.
authors.affiliation: La Trobe Institute for Molecular Science, La Trobe University, Australia.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Shahmiri
authors.affiliation: La Trobe Institute for Molecular Science, La Trobe University, Australia.
authors.forename: Marta
authors.initials: M
authors.lastname: Enciso
authors.affiliation: La Trobe Institute for Molecular Science, La Trobe University, Australia.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Adda
authors.affiliation: La Trobe Institute for Molecular Science, La Trobe University, Australia.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Smith
authors.affiliation: La Trobe Institute for Molecular Science, La Trobe University, Australia.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Perugini
authors.affiliation: La Trobe Institute for Molecular Science, La Trobe University, Australia.
authors.forename: Adam
authors.initials: A
authors.lastname: Mechler
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects* / Q000648:ultrastructure; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry; D008563:Membrane Lipids / Q000737:chemistry; D046529:Microscopy, Electron, Transmission; D057139:Nanofibers / Q000737:chemistry* / Q000648:ultrastructure; D010743:Phospholipids / Q000737:chemistry; D016062:Porosity / Q000187:drug effects; D017433:Protein Structure, Secondary; D054804:Cathelicidins
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; D008563:Membrane Lipids; D010743:Phospholipids; D054804:Cathelicidins