Jun 19, 2002

Synthetic lipoteichoic acid from Staphylococcus aureus is a potent stimulus of cytokine release

The Journal of Experimental Medicine
Siegfried MorathThomas Hartung

Abstract

We recently purified lipoteichoic acid (LTA) from Staphylococcus aureus to more than 99% purity by a novel preparation method and deduced its structure with the first nuclear magnetic resonance (NMR) of a complete LTA. In contrast to Gram-negative lipopolysaccharides, this LTA requires the toll-like receptor (TLR)-2 and not TLR-4 for cytokine induction in monocytes and macrophages. To elucidate the structure-function relationships for LTA from S. aureus, the lipid anchor was prepared by either acidic hydrolysis of native LTA or chemical synthesis (gentiobiosyl-sn-dimyristoylglycerol). Next, a complete LTA molecule with six glycerophosphate units carrying four alanine plus one N-acetyl-glucosamine substituent was synthesized, which displayed the same potency to activate monocytes as native LTA. However, 100-1,000 times higher concentrations of the lipid anchor were required for cytokine induction. It is worthy to note that replacing D-alanine with L-alanine blunted the effect indicating stereoselective recognition. The structure identification of this synthesized and biologically active LTA was proven by NMR and matrix-assisted laser desorption-ionization mass spectrometry. We concluded that the lipid anchor, with its fatty acid...Continue Reading

Mentioned in this Paper

Macrophages, Peritoneal
Surface Enhanced Laser Desorption Ionization Mass Spectrometry
In Vivo NMR Spectroscopy
TLR4 gene
RNA Chemical Synthesis
Magnetic Resonance Imaging
Thylacodes aureus
Toll-Like Receptor 2
Mice, Inbred C3H
Styrax aureus

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