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Structure-function relationship of cytokine induction by lipoteichoic acid from Staphylococcus aureus
1Department of Biochemical Pharmacology, University of Konstanz, D-78457 Konstanz, Germany.
The Journal of Experimental Medicine
|February 7, 2001
Summary
Pure lipoteichoic acids (LTAs) from Staphylococcus aureus are potent immunostimulators. Standard purification methods remove alanine substituents, reducing LTA
Area of Science:
- Immunology
- Microbiology
- Biochemistry
Background:
- Lipoteichoic acids (LTAs) are proposed immunostimulatory molecules in Gram-positive bacteria.
- Staphylococcus aureus LTA, despite its clinical relevance, was previously found inactive after purification.
Purpose of the Study:
- To develop a novel isolation procedure for biologically active LTA from S. aureus.
- To perform the first structural analysis of purified, active LTA.
- To investigate the role of alanine substituents in LTA's immunostimulatory activity.
Main Methods:
- Novel LTA isolation procedure.
- Nuclear magnetic resonance (NMR) and mass spectrometry for structural analysis.
- Comparison of LTA purified by standard vs. novel methods.
- Assessment of cytokine induction activity.
- Chemical hydrolysis of alanine substituents.
Main Results:
- A novel method yielded pure (>99%) biologically active LTA.
- Standard purification methods lead to loss of alanine substituents.
- Loss of alanine substituents attenuates LTA's cytokine induction activity.
- Active LTA's cytokine induction was abolished upon alanine substituent hydrolysis.
Conclusions:
- Lipoteichoic acids (LTAs) are major immunostimulatory components of Staphylococcus aureus.
- Alanine substituents are critical for LTA's ability to induce cytokines.
- A refined purification protocol is essential for studying LTA's biological activity.