title: Interactions of lipopolysaccharide with lipid membranes, raft models - a solid state NMR study.
abstract: Lipopolysaccharide (LPS) is a major component of the external leaflet of bacterial outer membranes, key pro-inflammatory factor and an important mediator of host-pathogen interactions. In host cells it activates the complement along with a pro-inflammatory response via a TLR4-mediated signalling cascade and shows preference for cholesterol-containing membranes. Here, we use solid state (13)C and (31)P MAS NMR to investigate the interactions of LPS from three bacterial species, Brucella melitensis, Klebsiella pneumoniae and Escherichia coli, with mixed lipid membranes, raft models. All endotoxin types are found to be pyrophosphorylated and Klebsiellar LPS is phosphonylated, as well. Carbon-13 MAS NMR indicates an increase in lipid order in the presence of LPS. Longitudinal (31)P relaxation, providing a direct probe of LPS molecular and segmental mobility, reveals a significant reduction in (31)P T1 times and lower molecular mobility in the presence of ternary lipid mixtures. Along with the ordering effect on membrane lipid, this suggests a preferential partitioning of LPS into ordered bilayer sphingomyelin/cholesterol-rich domains. We hypothesise that this is an important evolutionary drive for the selection of GPI-anchored raft-associated LPS-binding proteins as a first line of response to membrane-associated LPS.
authors.affiliation: School of Biomedical Sciences, University of Nottingham, Nottingham NG7 2UH, UK.
authors.forename: Filip
authors.initials: F
authors.lastname: Ciesielski
authors.forename: David C
authors.initials: DC
authors.lastname: Griffin
authors.forename: Michael
authors.initials: M
authors.lastname: Rittig
authors.forename: Ignacio
authors.initials: I
authors.lastname: Moriyón
authors.forename: Boyan B
authors.initials: BB
authors.lastname: Bonev
mesh_terms: D017347:Brucella melitensis / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism*; D004926:Escherichia coli / Q000502:physiology; D054884:Host-Pathogen Interactions; D007711:Klebsiella pneumoniae / Q000502:physiology; D008051:Lipid Bilayers / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008563:Membrane Lipids / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism*; D008958:Models, Molecular; D010743:Phospholipids / Q000378:metabolism*
chemical_list: D008051:Lipid Bilayers; D008070:Lipopolysaccharides; D008563:Membrane Lipids; D010743:Phospholipids