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 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 ␣-(234)-linked 3-deoxy-Dmanno-oct-2-ulosonic acid disaccharide. Lipid A is a pentaacylated ␤-(1 36)-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.

Inhibition of toll‐like receptor 4 breaks the inflammatory loop in autoimmune destructive arthritis

“…The antagonistic activity of this LPS is probably caused by the cylindrical conformation of its lipid A due to the presence of a long-chain fatty acid, a characteristic that has been described for Bartonella henselae LPS and is known to reduce endotoxicity of LPS (38). Long-chain fatty acids are also present in other types of LPS with TLR-4-antagonistic properties, such as LPS of Helicobacter pylori and Rhodobacter capsulatus (39,40).…”

Predominant Outer Membrane Antigens of Bartonella henselae

“…Bartonella LPS, however, does not induce the production of tumor necrosis factor alpha (23) and has low endotoxic activity as measured by toll-like receptor 2 signaling (41). This atypical host response to Bartonella LPS is most probably due to an unusual composition of the lipid A and attached long-chain fatty acids (11,14,41). The altered LPS of Bartonella may be responsible for the pathogen's ability to establish persistent bacteremic infections without causing significant clinical pathology within the host.…”

Strategies of exploitation of mammalian reservoirs by Bartonella species

“…A further mechanism by which bartonellae may counteract the threat of host immunity is via lipopolysaccharide (LPS) modification. The LPS of B. henselae possesses an unusual penta-acylated lipid A with a longchain fatty acid [61], a modification that may attenuate toll-like receptor (TLR) 4-mediated host response to bartonellae endotoxin [61,62]. …”