Invasive Staphylococcus epidermidis uses a unique processive wall teichoic acid glycosyltransferase to evade immune recognition

Science Advances, vol. 9, pp. eadj2641

Abstract

Staphylococcus epidermidis expresses glycerol phosphate wall teichoic acid (WTA), but some health care–associated methicillin-resistant S. epidermidis (HA-MRSE) clones produce a second, ribitol phosphate (RboP) WTA, resembling that of the aggressive pathogen Staphylococcus aureus . RboP-WTA promotes HA-MRSE persistence and virulence in bloodstream infections. We report here that the TarM enzyme of HA-MRSE [TarM(Se)] glycosylates RboP-WTA with glucose, instead of N -acetylglucosamine (GlcNAc) by TarM(Sa) in S. aureus . Replacement of GlcNAc with glucose in RboP-WTA impairs HA-MRSE detection by human immunoglobulin G, which may contribute to the immune-evasion capacities of many invasive S. epidermidis . Crystal structures of complexes with uridine diphosphate glucose (UDP-glucose), and with UDP and glycosylated poly(RboP), reveal the binding mode and glycosylation mechanism of this enzyme and explain why TarM(Se) and TarM(Sa) link different sugars to poly(RboP). These structural data provide evidence that TarM(Se) is a processive WTA glycosyltransferase. Our study will support the targeted inhibition of TarM enzymes, and the development of RboP-WTA targeting vaccines and phage therapies.

Authors 11

1. Yinglan Guo corresponding

   University of Tübingen

   Affiliation as printed

   Cluster of Excellence “Controlling Microbes to Fight Infections (CMFI)”, University of Tübingen, Tübingen, Germany

   Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany

2. Xin Du corresponding

   German Center for Infection Research · University of Tübingen

   Affiliation as printed

   Cluster of Excellence “Controlling Microbes to Fight Infections (CMFI)”, University of Tübingen, Tübingen, Germany

   German Centre for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany

   Interfaculty Institute of Microbiology and Infection Medicine Tübingen, Infection Biology, University of Tübingen, Tübingen, Germany

3. Janes Krusche

   German Center for Infection Research · University of Tübingen

   Affiliation as printed

   Cluster of Excellence “Controlling Microbes to Fight Infections (CMFI)”, University of Tübingen, Tübingen, Germany

   German Centre for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany

   Interfaculty Institute of Microbiology and Infection Medicine Tübingen, Infection Biology, University of Tübingen, Tübingen, Germany

4. Christian Beck

   German Center for Infection Research · University of Tübingen

   Affiliation as printed

   Cluster of Excellence “Controlling Microbes to Fight Infections (CMFI)”, University of Tübingen, Tübingen, Germany

   German Centre for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany

   Interfaculty Institute of Microbiology and Infection Medicine Tübingen, Infection Biology, University of Tübingen, Tübingen, Germany

5. Sara Ali Aachen

   Leiden University

   Affiliation as printed

   Leiden Institute of Chemistry, Leiden University, Leiden, Netherlands

6. Axel Walter

   University of Tübingen

   Affiliation as printed

   Cluster of Excellence “Controlling Microbes to Fight Infections (CMFI)”, University of Tübingen, Tübingen, Germany

   Interfaculty Institute of Microbiology and Infection Medicine Tübingen, Organismic Interactions/Glycobiology, University of Tübingen, Tübingen, Germany

7. Volker Winstel

   German Center for Infection Research · University of Tübingen

   Affiliation as printed

   German Centre for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany

   Interfaculty Institute of Microbiology and Infection Medicine Tübingen, Infection Biology, University of Tübingen, Tübingen, Germany

8. Christoph A. Mayer

   University of Tübingen

   Affiliation as printed

   Cluster of Excellence “Controlling Microbes to Fight Infections (CMFI)”, University of Tübingen, Tübingen, Germany

   Interfaculty Institute of Microbiology and Infection Medicine Tübingen, Organismic Interactions/Glycobiology, University of Tübingen, Tübingen, Germany

9. Jeroen D. C. Codée Aachen

   Leiden University

   Affiliation as printed

   Leiden Institute of Chemistry, Leiden University, Leiden, Netherlands

10. Andreas Peschel corresponding

    German Center for Infection Research · University of Tübingen

    Affiliation as printed

    Cluster of Excellence “Controlling Microbes to Fight Infections (CMFI)”, University of Tübingen, Tübingen, Germany

    German Centre for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany

    Interfaculty Institute of Microbiology and Infection Medicine Tübingen, Infection Biology, University of Tübingen, Tübingen, Germany

11. Thilo Stehle corresponding

    University of Tübingen

    Affiliation as printed

    Cluster of Excellence “Controlling Microbes to Fight Infections (CMFI)”, University of Tübingen, Tübingen, Germany

    Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany