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

Siegfried Morath, Andreas Stadelmaier, Armin Geyer, Richard R. Schmidt, Thomas Hartung

Research output: Contribution to journalArticlepeer-review

201 Scopus citations


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 acids, represents an integral part of the immunostimulatory activity of LTA, but requires additional structural components on the polyglycerophosphate backbone.

Original languageEnglish (US)
Pages (from-to)1635-1640
Number of pages6
JournalJournal of Experimental Medicine
Issue number12
StatePublished - Jun 17 2002
Externally publishedYes


  • Chemistry, organic
  • Gram-positive bacteria
  • Immunity, natural
  • Structure-activity relationship
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


Dive into the research topics of 'Synthetic lipoteichoic acid from Staphylococcus aureus is a potent stimulus of cytokine release'. Together they form a unique fingerprint.

Cite this