Brief Definitive Report

Structure–Function Relationship of Cytokine Induction by Lipoteichoic Acid from Staphylococcus aureus

Correspondence to: Thomas Hartung, University of Konstanz, Biochemical Pharmacology, 78457 Konstanz, Germany. Tel:49-7531-884116 Fax:49-7531-884117 E-mail:Thomas.Hartung{at}uni-konstanz.de.

Lipoteichoic acids (LTAs) have been proposed as putative Gram-positive immunostimulatory counterparts to Gram-negative lipopolysaccharides. However, LTA from Staphylococcus aureus, the clinically most frequent Gram-positive pathogen, was inactive after purification. Here, a novel isolation procedure to prepare pure (>99%) biologically active LTA, allowing the first structural analysis by nuclear magnetic resonance and mass spectrometry, is described. A comparison with LTA purified by standard techniques revealed that alanine substituents are lost during standard purification, resulting in attenuated cytokine induction activity. In line with this finding, hydrolysis of alanine substituents of active LTA decimated cytokine induction. LTA represents a major immunostimulatory component of S. aureus.

Key Words: magnetic resonance spectroscopy, tumor necrosis factor, gram-positive bacteria, isolation and purification, immunity, natural

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• Almeida, I. C., Gazzinelli, R. T. (2001). Proinflammatory activity of glycosylphosphatidylinositol anchors derived from Trypanosoma cruzi: structural and functional analyses. J. Leukoc. Biol. 70: 467-477 [Abstract] [Full Text]  
• Gargir, A., Ofek, I., Hasty, D., Meron-Sudai, S., Tsubery, H., Keisari, Y., Nissim, A. (2001). Inhibition of antibody-dependent stimulation of lipoteichoic acid-treated human monocytes and macrophages by polyglycerolphosphate-reactive peptides. J. Leukoc. Biol. 70: 537-542 [Abstract] [Full Text]  
• Stuyt, R. J. L., Netea, M. G., Kim, S.-H., Novick, D., Rubinstein, M., Kullberg, B.-J., Van der Meer, J. W. M., Dinarello, C. A. (2001). Differential Roles of Interleukin-18 (IL-18) and IL-12 for Induction of Gamma Interferon by Staphylococcal Cell Wall Components and Superantigens. Infect. Immun. 69: 5025-5030 [Abstract] [Full Text]  
• Opitz, B., Schroder, N. W. J., Spreitzer, I., Michelsen, K. S., Kirschning, C. J., Hallatschek, W., Zahringer, U., Hartung, T., Gobel, U. B., Schumann, R. R. (2001). Toll-like Receptor-2 Mediates Treponema Glycolipid and Lipoteichoic Acid-induced NF-kappa B Translocation. J. Biol. Chem. 276: 22041-22047 [Abstract] [Full Text]  

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