Structure-function relationship of cytokine induction by lipoteichoic acid from Staphylococcus aureus.
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.
Morath
S
S
Department of Biochemical Pharmacology, University of Konstanz, D-78457 Konstanz, Germany.
Geyer
A
A
Hartung
T
T
D000117:Acetylglucosamine / Q000737:chemistry / Q000276:immunology; D000409:Alanine / Q000737:chemistry / Q000276:immunology; D006801:Humans; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D013058:Mass Spectrometry / Q000379:methods; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D013211:Staphylococcus aureus / Q000737:chemistry / Q000276:immunology*; D013329:Structure-Activity Relationship; D013682:Teichoic Acids / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D008070:Lipopolysaccharides; D013682:Teichoic Acids; D014409:Tumor Necrosis Factor-alpha; C009900:lipoteichoic acid; D000409:Alanine; D000117:Acetylglucosamine