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 lipopalysaccharide. Here, we show that B. henselae ATCC 49882T produces a deep-rough-type lipopolysaccharide devoid of O-chain and report on its complete structure and Toll-like receptordependent 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 α-(2→4)-linked 3-deoxy-D-manno-oct-2-ulosonic acid disaccharide. Lipid A is a pentaacylated β-(1′→6)-linked 2,3-diamino-2,3-dideoxyglucose disaccharide 1,4′-bisphosphate with two amidelinked 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. [ABSTRACT FROM AUTHOR]