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

J Infect Dis. 2003 Aug 1;188(3):414-23. doi: 10.1086/376533. Epub 2003 Jul 10.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • 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