Methicillin resistance in Staphylococcus aureus requires glycosylated wall teichoic acids

Proc Natl Acad Sci U S A. 2012 Nov 13;109(46):18909-14. doi: 10.1073/pnas.1209126109. Epub 2012 Oct 1.


Staphylococcus aureus peptidoglycan (PG) is densely functionalized with anionic polymers called wall teichoic acids (WTAs). These polymers contain three tailoring modifications: d-alanylation, α-O-GlcNAcylation, and β-O-GlcNAcylation. Here we describe the discovery and biochemical characterization of a unique glycosyltransferase, TarS, that attaches β-O-GlcNAc (β-O-N-acetyl-D-glucosamine) residues to S. aureus WTAs. We report that methicillin resistant S. aureus (MRSA) is sensitized to β-lactams upon tarS deletion. Unlike strains completely lacking WTAs, which are also sensitive to β-lactams, ΔtarS strains have no growth or cell division defects. Because neither α-O-GlcNAc nor β-O-Glucose modifications can confer resistance, the resistance phenotype requires a highly specific chemical modification of the WTA backbone, β-O-GlcNAc residues. These data suggest β-O-GlcNAcylated WTAs scaffold factors required for MRSA resistance. The β-O-GlcNAc transferase identified here, TarS, is a unique target for antimicrobials that sensitize MRSA to β-lactams.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / antagonists & inhibitors
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Cell Wall / genetics
  • Cell Wall / metabolism*
  • Gene Deletion
  • Glycosylation
  • Glycosyltransferases / antagonists & inhibitors
  • Glycosyltransferases / genetics
  • Glycosyltransferases / metabolism*
  • Humans
  • Methicillin Resistance / physiology*
  • Methicillin-Resistant Staphylococcus aureus / enzymology*
  • Methicillin-Resistant Staphylococcus aureus / genetics
  • Teichoic Acids / genetics
  • Teichoic Acids / metabolism*
  • beta-Lactams / pharmacology


  • Bacterial Proteins
  • Teichoic Acids
  • beta-Lactams
  • Glycosyltransferases