title: Pathways and roles of wall teichoic acid glycosylation in Staphylococcus aureus.
abstract: The thick peptidoglycan layers of Gram-positive bacteria are connected to polyanionic glycopolymers called wall teichoic acids (WTA). Pathogens such as Staphylococcus aureus, Listeria monocytogenes, or Enterococcus faecalis produce WTA with diverse, usually strain-specific structure. Extensive studies on S. aureus WTA mutants revealed important functions of WTA in cell division, growth, morphogenesis, resistance to antimicrobials, and interaction with host or phages. While most of the S. aureus WTA-biosynthetic genes have been identified it remained unclear for long how and why S. aureus glycosylates WTA with α- or β-linked N-acetylglucosamine (GlcNAc). Only recently the discovery of two WTA glycosyltransferases, TarM and TarS, yielded fundamental insights into the roles of S. aureus WTA glycosylation. Mutants lacking WTA GlcNAc are resistant towards most of the S. aureus phages and, surprisingly, TarS-mediated WTA β-O-GlcNAc modification is essential for β-lactam resistance in methicillin-resistant S. aureus. Notably, S. aureus WTA GlcNAc residues are major antigens and activate the complement system contributing to opsonophagocytosis. WTA glycosylation with a variety of sugars and corresponding glycosyltransferases were also identified in other Gram-positive bacteria, which paves the way for detailed investigations on the diverse roles of WTA modification with sugar residues.
authors.affiliation: Cellular and Molecular Microbiology Division, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Elfriede-Aulhorn-Straße 6, 72076 Tübingen, Germany; German Center for Infection Research (DZIF), partner site Tübingen, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Winstel
authors.affiliation: Cellular and Molecular Microbiology Division, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Elfriede-Aulhorn-Straße 6, 72076 Tübingen, Germany; German Center for Infection Research (DZIF), partner site Tübingen, Germany. Electronic address: guoqing.xia@med.uni-tuebingen.de.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Xia
authors.affiliation: Cellular and Molecular Microbiology Division, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Elfriede-Aulhorn-Straße 6, 72076 Tübingen, Germany; German Center for Infection Research (DZIF), partner site Tübingen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Peschel
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism*; D002473:Cell Wall / Q000201:enzymology / Q000378:metabolism*; D055786:Gene Knockout Techniques; D006031:Glycosylation; D016695:Glycosyltransferases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D013204:Staphylococcus Phages / Q000502:physiology*; D013211:Staphylococcus aureus / Q000201:enzymology / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D013682:Teichoic Acids / Q000276:immunology / Q000378:metabolism*; D053585:Virus Attachment; D018440:beta-Lactam Resistance
chemical_list: D000942:Antigens, Bacterial; D013682:Teichoic Acids; D016695:Glycosyltransferases
keywords: Bacteriophage; Glycoepitopes; S. aureus; Wall teichoic acid; β-Lactam resistance