Methicillin resistance in Staphylococcus aureus requires glycosylated wall teichoic acids

Stephanie Brown, Guoqing Xia, Lyly G. Luhachack, Jennifer Campbell, Timothy C. Meredith, Calvin Chen, Volker Winstel, Cordula Gekeler, Javier E. Irazoqui, Andreas Peschel, Suzanne Walker

Research output: Contribution to journalArticlepeer-review

141 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)18909-18914
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number46
DOIs
StatePublished - Nov 13 2012

All Science Journal Classification (ASJC) codes

  • General

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