title: 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.affiliation: Microbial Genetics, University of Tübingen, Tübingen, Germany.
authors.forename: Sascha A
authors.initials: SA
authors.lastname: Kristian
authors.forename: Xavier
authors.initials: X
authors.lastname: Lauth
authors.forename: Victor
authors.initials: V
authors.lastname: Nizet
authors.forename: Friedrich
authors.initials: F
authors.lastname: Goetz
authors.forename: Birgid
authors.initials: B
authors.lastname: Neumeister
authors.forename: Andreas
authors.initials: A
authors.lastname: Peschel
authors.forename: Regine
authors.initials: R
authors.lastname: Landmann
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001430:Bacteriocins; D054426:Chemokine CXCL2; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000276:immunology / Q000382:microbiology; D007958:Leukocyte Count; D007962:Leukocytes / Q000276:immunology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015846:Monokines / Q000032:analysis; D009154:Mutation; D010455:Peptides; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013203:Staphylococcal Infections / Q000097:blood / Q000276:immunology*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development / Q000472:pathogenicity*; D013682:Teichoic Acids / Q000276:immunology* / Q000378:metabolism; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014774:Virulence
chemical_list: D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D054426:Chemokine CXCL2; D008562:Membrane Glycoproteins; D015846:Monokines; D010455:Peptides; D011956:Receptors, Cell Surface; D013682:Teichoic Acids; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; C057656:gallidermin