TY - JOUR
T1 - Interactions of lipopolysaccharide with lipid membranes, raft models - A solid state NMR study
AU - Ciesielski, Filip
AU - Griffin, David C.
AU - Rittig, Michael
AU - Moriyón, Ignacio
AU - Bonev, Boyan B.
N1 - Funding Information:
The authors would like to acknowledge financial support from the UK Biotechnology and Biological Sciences Research Council (grant BB/C510924 ) to BBB and the generous contribution from Varian Ltd. Research in the laboratory of IM is supported by grants from FIMA and Ministerio de Ciencia y Tecnología of Spain ( AGL2011-30453-C04 ). FC is supported through a DTA studentship to BBB and MR from the Medical Research Council . We also thank Dr Evgeny Vinogradov for his advice on LPS core structure.
PY - 2013
Y1 - 2013
N2 - 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 13C and 31P 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 31P relaxation, providing a direct probe of LPS molecular and segmental mobility, reveals a significant reduction in 31P 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.
AB - 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 13C and 31P 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 31P relaxation, providing a direct probe of LPS molecular and segmental mobility, reveals a significant reduction in 31P 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.
KW - Endotoxin
KW - High resolution solid state NMR
KW - Host-pathogen interactions
KW - LPS
KW - Lipid domains
KW - Longitudinal relaxation
UR - http://www.scopus.com/inward/record.url?scp=84877046140&partnerID=8YFLogxK
U2 - 10.1016/j.bbamem.2013.03.029
DO - 10.1016/j.bbamem.2013.03.029
M3 - Article
C2 - 23567915
AN - SCOPUS:84877046140
SN - 0005-2736
VL - 1828
SP - 1731
EP - 1742
JO - Biochimica et Biophysica Acta - Biomembranes
JF - Biochimica et Biophysica Acta - Biomembranes
IS - 8
ER -
