title: Spectroscopic investigations of the binding mechanisms between antimicrobial peptides and membrane models of Pseudomonas aeruginosa and Klebsiella pneumoniae.
abstract: CD spectroscopy was used to investigate the interactions of a series of synthetic AMPs with LPS isolated from Pseudomonas aeruginosa and Klebsiella pneumoniae, as well as with various phospholipids to better approximate the chemical composition of the membranes of these two strains of Gram-negative bacteria. This investigation was conducted in order to probe how the contributions of key physicochemical properties of an AMP vary in different regions of the membranes of these two bacteria. The conclusions from this study are as follows. (1) The binding interactions between the AMP and the membranes are defined by the complementarity of delocalization of positive charge density of the basic amino side chains (i.e., electrostatics), molecular flexibility of the peptide backbone, and overall hydrophobicity. (2) The binding interactions of these AMPs to LPS seem to be predominantly with the lipid A region of the LPS. (3) Incorporation of phospholipids into the LPS containing SUVs resulted in dramatic changes in the conformational equilibrium of the bound AMPs. (4) For the LPS-phospholipid models of Pseudomonas aeruginosa, delocalization of the side chain positive charge plays a major role in determining the number of conformers that contribute to the binding conformational equilibrium. This relationship was not observed for the models of the outer and inner membranes of Klebsiella pneumoniae.
authors.affiliation: Department of Chemistry, East Carolina University, Science and Technology Building, Greenville, NC 27858, United States.
authors.forename: Hanbo
authors.initials: H
authors.lastname: Chai
authors.affiliation: Department of Chemistry, East Carolina University, Science and Technology Building, Greenville, NC 27858, United States.
authors.forename: William E
authors.initials: WE
authors.lastname: Allen
authors.affiliation: Department of Chemistry, East Carolina University, Science and Technology Building, Greenville, NC 27858, United States. Electronic address: rhicks@gru.edu.
authors.forename: Rickey P
authors.initials: RP
authors.lastname: Hicks
mesh_terms: D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D002473:Cell Wall / Q000378:metabolism*; D002942:Circular Dichroism; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000737:chemistry / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D008969:Molecular Sequence Data; D011485:Protein Binding; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D008070:Lipopolysaccharides; D008081:Liposomes
keywords: Antimicrobial peptides; Circular dichroism spectroscopy; Klebsiella pneumoniae; Lipopolysaccharides; Membrane models; Pseudomonas aeruginosa