Structure and biological activity of the short-chain lipopolysaccharide from Bartonella henselae ATCC 49882T.
The facultative intracellular pathogen Bartonella henselae is responsible for a broad range of clinical manifestations, including the formation of vascular tumors as a result of increased proliferation and survival of colonized endothelial cells. This remarkable interaction with endotoxin-sensitive endothelial cells and the apparent lack of septic shock are considered to be due to a reduced endotoxic activity of the B. henselae lipopolysaccharide. Here, we show that B. henselae ATCC 49882(T) produces a deep-rough-type lipopolysaccharide devoid of O-chain and report on its complete structure and Toll-like receptor-dependent biological activity. The major short-chain lipopolysaccharide was studied by chemical analyses, electrospray ionization, and matrix-assisted laser desorption/ionization mass spectrometry, as well as by NMR spectroscopy after alkaline deacylation. The carbohydrate portion of the lipopolysaccharide consists of a branched trisaccharide containing a glucose residue attached to position 5 of an alpha-(2-->4)-linked 3-deoxy-d-manno-oct-2-ulosonic acid disaccharide. Lipid A is a pentaacylated beta-(1'-->6)-linked 2,3-diamino-2,3-dideoxy-glucose disaccharide 1,4'-bisphosphate with two amide-linked residues each of 3-hydroxydodecanoic and 3-hydroxyhexadecanoic acids and one residue of either 25-hydroxyhexacosanoic or 27-hydroxyoctacosanoic acid that is O-linked to the acyl group at position 2'. The lipopolysaccharide studied activated Toll-like receptor 4 signaling only to a low extent (1,000-10,000-fold lower compared with that of Salmonella enterica sv. Friedenau) and did not activate Toll-like receptor 2. Some unusual structural features of the B. henselae lipopolysaccharide, including the presence of a long-chain fatty acid, which are shared by the lipopolysaccharides of other bacteria causing chronic intracellular infections (e.g. Legionella and Chlamydia), may provide the molecular basis for low endotoxic potency.
Zähringer
Ulrich
U
Research Center Borstel, Leibniz-Center for Medicine and Biosciences, 23845 Borstel, Germany. uzaehr@fz-borstel.de
Lindner
Buko
B
Knirel
Yuriy A
YA
van den Akker
Willem M R
WM
Hiestand
Rosemarie
R
Heine
Holger
H
Dehio
Christoph
C
D001474:Bartonella Infections; D018416:Bartonella henselae / Q000737:chemistry* / Q000276:immunology / Q000302:isolation & purification; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008070:Lipopolysaccharides / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D008745:Methylation; D008969:Molecular Sequence Data; D021241:Spectrometry, Mass, Electrospray Ionization; D014162:Transfection
D008070:Lipopolysaccharides