title: Wall Teichoic Acid Glycosylation Governs Staphylococcus aureus Nasal Colonization.
abstract: Nasal colonization by the human pathogen Staphylococcus aureus is a major risk factor for hospital- and community-acquired infections. A key factor required for nasal colonization is a cell surface-exposed zwitterionic glycopolymer, termed wall teichoic acid (WTA). However, the precise mechanisms that govern WTA-mediated nasal colonization have remained elusive. Here, we report that WTA GlcNAcylation is a pivotal requirement for WTA-dependent attachment of community-acquired methicillin-resistant S. aureus (MRSA) and emerging livestock-associated MRSA to human nasal epithelial cells, even under conditions simulating the nutrient composition and dynamic flow of nasal secretions. Depending on the S. aureus strain, WTA O-GlcNAcylation occurs in either α or β configuration, which have similar capacities to mediate attachment to human nasal epithelial cells, suggesting that many S. aureus strains maintain redundant pathways to ensure appropriate WTA glycosylation. Strikingly, a lack of WTA glycosylation significantly abrogated the ability of MRSA to colonize cotton rat nares in vivo. These results indicate that WTA glycosylation modulates S. aureus nasal colonization and may help to develop new strategies for eradicating S. aureus nasal colonization in the future.
  
  
  OBJECTIVE
  Nasal colonization by the major human pathogen Staphylococcus aureus is a risk factor for severe endogenous infections and contributes to the spread of this microbe in hospitals and the community. Here, we show that wall teichoic acid (WTA) O-GlcNAcylation is a key factor required for S. aureus nasal colonization. These data provide a mechanistic explanation for the capacity of WTA to modulate S. aureus nasal colonization and may stimulate research activities to establish valuable strategies to eradicate S. aureus nasal colonization in high-risk hospitalized patients and in the general community.
authors.forename: Volker
authors.initials: V
authors.lastname: Winstel
authors.forename: Petra
authors.initials: P
authors.lastname: Kühner
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Salomon
authors.affiliation: Microbiology and Infection Control, Statens Serum Institute, Copenhagen, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Larsen
authors.affiliation: Microbiology and Infection Control, Statens Serum Institute, Copenhagen, Denmark.
authors.forename: Robert
authors.initials: R
authors.lastname: Skov
authors.affiliation: Institute for Tropical Medicine, University of Tübingen, Tübingen, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hoffmann
authors.affiliation: andreas.peschel@uni-tuebingen.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Peschel
authors.forename: Christopher
authors.initials: C
authors.lastname: Weidenmaier
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D002353:Carrier State / Q000382:microbiology*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000382:microbiology; D006031:Glycosylation; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D023421:Models, Animal; D009297:Nasal Mucosa / Q000382:microbiology*; D016205:Sigmodontinae; D013203:Staphylococcal Infections / Q000382:microbiology*; D013682:Teichoic Acids / Q000378:metabolism*
chemical_list: D013682:Teichoic Acids