title: Binding interactions of bacterial lipopolysaccharide and the cationic amphiphilic peptides polymyxin B and WLBU2.
abstract: Passage of blood through a sorbent device for removal of bacteria and endotoxin by specific binding with immobilized, membrane-active, bactericidal peptides holds promise for treating severe blood infections. Peptide insertion in the target membrane and rapid/strong binding is desirable, while membrane disruption and release of degradation products to the circulating blood is not. Here we describe interactions between bacterial endotoxin (lipopolysaccharide, LPS) and the membrane-active, bactericidal peptides WLBU2 and polymyxin B (PmB). Analysis of the interfacial behavior of mixtures of LPS and peptide using air-water interfacial tensiometry and optical waveguide lightmode spectroscopy strongly suggests insertion of intact LPS vesicles by the peptide WLBU2 without vesicle destabilization. In contrast, dynamic light scattering (DLS) studies show that LPS vesicles appear to undergo peptide-induced destabilization in the presence of PmB. Circular dichroism spectra further confirm that WLBU2, which shows disordered structure in aqueous solution and substantially helical structure in membrane-mimetic environments, is stably located within the LPS membrane in peptide-vesicle mixtures. We therefore expect that presentation of WLBU2 at an interface, if tethered in a fashion which preserves its mobility and solvent accessibility, will enable the capture of bacteria and endotoxin without promoting reintroduction of endotoxin to the circulating blood, thus minimizing adverse clinical outcomes. On the other hand, our results suggest no such favorable outcome of LPS interactions with polymyxin B.
authors.affiliation: School of Chemical, Biological and Environmental Engineering, Oregon State University, Corvallis, OR 97331, United States.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Ryder
authors.affiliation: School of Chemical, Biological and Environmental Engineering, Oregon State University, Corvallis, OR 97331, United States.
authors.forename: Xiangming
authors.initials: X
authors.lastname: Wu
authors.affiliation: School of Chemical, Biological and Environmental Engineering, Oregon State University, Corvallis, OR 97331, United States.
authors.forename: Greg R
authors.initials: GR
authors.lastname: McKelvey
authors.affiliation: School of Chemical, Biological and Environmental Engineering, Oregon State University, Corvallis, OR 97331, United States.
authors.forename: Joseph
authors.initials: J
authors.lastname: McGuire
authors.affiliation: School of Chemical, Biological and Environmental Engineering, Oregon State University, Corvallis, OR 97331, United States. Electronic address: karl.schilke@oregonstate.edu.
authors.forename: Karl F
authors.initials: KF
authors.lastname: Schilke
mesh_terms: D000327:Adsorption; D000388:Air; D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D002942:Circular Dichroism; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008070:Lipopolysaccharides / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010316:Particle Size; D011112:Polymyxin B / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D013500:Surface Tension / Q000187:drug effects; D013501:Surface-Active Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D014867:Water
chemical_list: D023181:Antimicrobial Cationic Peptides; D008070:Lipopolysaccharides; D013501:Surface-Active Agents; C520840:WLBU2 peptide; D014867:Water; D011112:Polymyxin B
keywords: Cationic amphiphilic peptides; Endotoxin; Interfacial tensiometry; Lipopolysaccharide; Polymyxin B; Sepsis; WLBU2