Alanylation of teichoic acids protects Staphylococcus aureus against Toll-like receptor 2-dependent host defense in a mouse tissue cage infection model.

Abstract

Staphylococcus aureus is inherently resistant to cationic antimicrobial peptides because of alanylation of cell envelope teichoic acids. To test the effect of alanylated teichoic acids on virulence and host defense mediated by Toll-like receptor 2 (TLR2), wild-type (wt) S. aureus ATCC35556 (S.a.113) and its isogenic mutant expressing unalanylated teichoic acids (dlt(-)) were compared in a tissue cage infection model that used C57BL/6 wt and TLR2-deficient mice. The minimum infective doses (MID) to establish persistent infection with S.a.113 were 10(3) and 10(2) colony-forming units (cfu) in wt and TLR2(-/-) mice, respectively. The corresponding MID for dlt(-) were 5x105 and 10(3) cfu in wt and TLR2(-/-) mice, respectively. Both mouse strains showed bacterial-load-dependent inflammation with elevations in tumor necrosis factor, macrophage inflammatory protein 2, and leukocytes, with increasing proportions of dead cells. These findings indicate that alanylated teichoic acids contribute to virulence of S. aureus, and TLR2 mediates host defense, which partly targets alanylated teichoic acids.

• Authors: Sascha A Kristian, Xavier Lauth, Victor Nizet, Friedrich Goetz, Birgid Neumeister, Andreas Peschel, Regine Landmann
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 188 Issue 3 Pg. 414-23 (Aug 01 2003) ISSN: 0022-1899 [Print] United States
• PMID: 12870123 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Bacteriocins
• Chemokine CXCL2
• Membrane Glycoproteins
• Monokines
• Peptides
• Receptors, Cell Surface
• Teichoic Acids
• Toll-Like Receptor 2
• Toll-Like Receptors
• Tumor Necrosis Factor-alpha
• gallidermin

Topics

• Animals
• Anti-Bacterial Agents (pharmacology)
• Bacteriocins
• Chemokine CXCL2
• Disease Models, Animal
• Female
• Inflammation (immunology, microbiology)
• Leukocyte Count
• Leukocytes (immunology)
• Membrane Glycoproteins (deficiency, genetics, physiology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Monokines (analysis)
• Mutation
• Peptides
• Receptors, Cell Surface (deficiency, genetics, physiology)
• Staphylococcal Infections (blood, immunology)
• Staphylococcus aureus (drug effects, growth & development, pathogenicity)
• Teichoic Acids (immunology, metabolism)
• Toll-Like Receptor 2
• Toll-Like Receptors
• Tumor Necrosis Factor-alpha (analysis)
• Virulence