期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2012
卷号：109
期号：46
页码：18909-18914
DOI：10.1073/pnas.1209126109
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Staphylococcus aureus peptidoglycan (PG) is densely functionalized with anionic polymers called wall teichoic acids (WTAs). These polymers contain three tailoring modifications: D-alanylation, -O-GlcNAcylation, and {beta}-O-GlcNAcylation. Here we describe the discovery and biochemical characterization of a unique glycosyltransferase, TarS, that attaches {beta}-O-GlcNAc ({beta}-O-N-acetyl-D-glucosamine) residues to S. aureus WTAs. We report that methicillin resistant S. aureus (MRSA) is sensitized to {beta}-lactams upon tarS deletion. Unlike strains completely lacking WTAs, which are also sensitive to {beta}-lactams, {Delta}tarS strains have no growth or cell division defects. Because neither -O-GlcNAc nor {beta}-O-Glucose modifications can confer resistance, the resistance phenotype requires a highly specific chemical modification of the WTA backbone, {beta}-O-GlcNAc residues. These data suggest {beta}-O-GlcNAcylated WTAs scaffold factors required for MRSA resistance. The {beta}-O-GlcNAc transferase identified here, TarS, is a unique target for antimicrobials that sensitize MRSA to {beta}-lactams.
