title: Membrane interactions of proline-rich antimicrobial peptide, Chex1-Arg20, multimers.
abstract: The increasing prevalence of antibiotic-resistant pathogens requires the development of new antibiotics. Proline-rich antimicrobial peptides (PrAMPs), including native apidaecins, Bac7, and oncocins or designed A3APO, show multi-modal actions against pathogens together with immunostimulatory activities. The interactions of the designed PrAMP, Chex1-Arg20, and its dimeric and tetrameric oligomers with different model membranes were investigated by circular dichroism spectroscopy, dynamic light scattering, zeta potential, differential scanning calorimetry, and dye leakage. Chex1-Arg20 oligomers showed stronger affinity and preferential binding to negatively charged phospholipid bilayers and led to lipid aggregation and neutralization. Fluorescence microscopy of negatively charged giant unilamellar vesicles with AlexFluor-647-labeled Chex1-Arg20 dimers and tetramers displayed aggregation at a peptide/lipid low ratio of 1:200 and at higher peptide concentrations (1:100/1:50) for Chex1-Arg20 monomer. Such interactions, aggregation, and neutralization of PrAMP oligomers additionally showed the importance of interactions of PrAMPs with negatively charged membranes.
authors.affiliation: School of Chemistry, Bio21 Institute, University of Melbourne, VIC 3010, Australia; The Florey Institute of Neuroscience and Mental Health, University of Melbourne, VIC 3010, Australia.
authors.forename: Wenyi
authors.initials: W
authors.lastname: Li
authors.affiliation: School of Chemistry, Bio21 Institute, University of Melbourne, VIC 3010, Australia.
authors.forename: Marc-Antoine
authors.initials: MA
authors.lastname: Sani
authors.affiliation: School of Chemistry, Bio21 Institute, University of Melbourne, VIC 3010, Australia.
authors.forename: Elaheh
authors.initials: E
authors.lastname: Jamasbi
authors.affiliation: Department of Biology, Temple University, Philadelphia, PA 19122, USA; Institute of Medical Microbiology, Semmelweis University, Budapest 1089, Hungary.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Otvos
authors.affiliation: School of Chemistry, Bio21 Institute, University of Melbourne, VIC 3010, Australia; The Florey Institute of Neuroscience and Mental Health, University of Melbourne, VIC 3010, Australia.
authors.forename: Mohammed Akhter
authors.initials: MA
authors.lastname: Hossain
authors.affiliation: School of Chemistry, Bio21 Institute, University of Melbourne, VIC 3010, Australia; The Florey Institute of Neuroscience and Mental Health, University of Melbourne, VIC 3010, Australia.
authors.forename: John D
authors.initials: JD
authors.lastname: Wade
authors.affiliation: School of Chemistry, Bio21 Institute, University of Melbourne, VIC 3010, Australia. Electronic address: fs@unimelb.edu.au.
authors.forename: Frances
authors.initials: F
authors.lastname: Separovic
mesh_terms: D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000737:chemistry / Q000378:metabolism*; D001704:Biopolymers / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002942:Circular Dichroism; D008051:Lipid Bilayers; D008564:Membrane Potentials; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D000890:Anti-Infective Agents; D001704:Biopolymers; D008051:Lipid Bilayers; D010455:Peptides
keywords: Chex1-Arg20 multimers; Lipid–peptide interactions; Liposomes; Phospholipid bilayers; Proline-rich antimicrobial peptides