title: Structure and biological activity of the short-chain lipopolysaccharide from Bartonella henselae ATCC 49882T.
abstract: 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.
authors.affiliation: Research Center Borstel, Leibniz-Center for Medicine and Biosciences, 23845 Borstel, Germany. uzaehr@fz-borstel.de
authors.forename: Ulrich
authors.initials: U
authors.lastname: Zähringer
authors.forename: Buko
authors.initials: B
authors.lastname: Lindner
authors.forename: Yuriy A
authors.initials: YA
authors.lastname: Knirel
authors.forename: Willem M R
authors.initials: WM
authors.lastname: van den Akker
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Hiestand
authors.forename: Holger
authors.initials: H
authors.lastname: Heine
authors.forename: Christoph
authors.initials: C
authors.lastname: Dehio
mesh_terms: 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
chemical_list: D008070:Lipopolysaccharides