Comparison of Lipoteichoic Acid from Different Serotypes of Streptococcus pneumoniae

Pneumococcal lipoteichoic acid (LTA) is known to have a completely different chemical structure compared with that of Staphylococcus aureus: the polyglycerophosphate in the backbone is replaced in the pneumococcal LTA by a pentamer repeating unit consisting of one ribitol and a tetrasaccharide carry...

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Published in:The Journal of biological chemistry 2006-11, Vol.281 (45), p.33849-33859
Main Authors: Draing, Christian, Pfitzenmaier, Markus, Zummo, Sebastiana, Mancuso, Giuseppe, Geyer, Armin, Hartung, Thomas, von Aulock, Sonja
Format: Article
Language:English
Subjects:
Animals
Bone Marrow Cells - metabolism
Cells, Cultured
Cytokines - metabolism
Granulocytes - metabolism
Humans
Lipopolysaccharides - isolation & purification
Lipopolysaccharides - pharmacology
Magnetic Resonance Spectroscopy
Mice
Mice, Inbred C3H
Neutrophils - drug effects
Serotyping
Staphylococcus aureus
Streptococcus pneumoniae
Streptococcus pneumoniae - chemistry
Streptococcus pneumoniae - classification
Teichoic Acids - isolation & purification
Teichoic Acids - pharmacology
Toll-Like Receptor 4 - metabolism
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Summary:Pneumococcal lipoteichoic acid (LTA) is known to have a completely different chemical structure compared with that of Staphylococcus aureus: the polyglycerophosphate in the backbone is replaced in the pneumococcal LTA by a pentamer repeating unit consisting of one ribitol and a tetrasaccharide carrying the unusual substituents phosphocholine and N-acetyl-d-galactosamine. Neither d-alanine nor N-acetyl-d-glucosamine, which play central roles in the biological activity of the staphylococcal LTA, has been reported. The extraction using butanol is more gentle compared with the previously reported chloroform-methanol extraction and results in a higher yield of LTA. We characterized the LTA of two different strains of Streptococcus pneumoniae:R6 (serotype 2) and Fp23 (serotype 4). NMR analysis confirmed the structure of LTA from R6 but showed that its ribitol carries an N-acetyl-d-galactosamine substituent. The NMR data for the LTA from Fp23 indicate that this LTA additionally contains ribitol-bound d-alanine. Dose-response curves of the two pneumococcal LTAs in human whole blood revealed that LTA from Fp23 was significantly more potent than LTA from R6 with regard to the induction of all cytokines measured (tumor necrosis factor, interleukin-1 (IL-1), IL-8, IL-10, granulocyte colony-stimulating factor, and interferon γ). However, other characteristics, such as lack of inhibition by endotoxin-specific LAL-F, Toll-like receptor 2 and not 4 dependence, and lack of stimulation of neutrophilic granulocytes, were shared by both LTAs. This is the first report of a difference in the structure of LTA between two pneumococcal serotypes resulting in different immunostimulatory potencies.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M602676200