title: Comparison of lipoteichoic acid from different serotypes of Streptococcus pneumoniae.
abstract: 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 gamma). 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.
authors.affiliation: Department of Biochemical Pharmacology, University of Konstanz, P. O. Box M668, 78457 Konstanz, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Draing
authors.forename: Markus
authors.initials: M
authors.lastname: Pfitzenmaier
authors.forename: Sebastiana
authors.initials: S
authors.lastname: Zummo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mancuso
authors.forename: Armin
authors.initials: A
authors.lastname: Geyer
authors.forename: Thomas
authors.initials: T
authors.lastname: Hartung
authors.forename: Sonja
authors.initials: S
authors.lastname: von Aulock
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000302:isolation & purification* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008809:Mice, Inbred C3H; D009504:Neutrophils / Q000187:drug effects; D012703:Serotyping; D013296:Streptococcus pneumoniae / Q000737:chemistry* / Q000145:classification; D013682:Teichoic Acids / Q000302:isolation & purification* / Q000494:pharmacology; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D013682:Teichoic Acids; D051197:Toll-Like Receptor 4; C009900:lipoteichoic acid