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Toll-like receptor 2 activation depends on lipopeptide shedding by bacterial surfactants

Author

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  • Dennis Hanzelmann

    (Interfaculty Institute for Microbiology and Infection Medicine Tübingen (IMIT), University of Tübingen)

  • Hwang-Soo Joo

    (Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Mirita Franz-Wachtel

    (Proteome Center Tübingen, Interfaculty Institute of Cell Biology, University of Tübingen)

  • Tobias Hertlein

    (Institute for Molecular Infection Biology, University of Würzburg)

  • Stefan Stevanovic

    (Interfaculty Institute for Cell Biology, Eberhard Karls University)

  • Boris Macek

    (Proteome Center Tübingen, Interfaculty Institute of Cell Biology, University of Tübingen)

  • Christiane Wolz

    (Interfaculty Institute for Microbiology and Infection Medicine Tübingen (IMIT), University of Tübingen)

  • Friedrich Götz

    (Interfaculty Institute for Microbiology and Infection Medicine Tübingen (IMIT), University of Tübingen)

  • Michael Otto

    (Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Dorothee Kretschmer

    (Interfaculty Institute for Microbiology and Infection Medicine Tübingen (IMIT), University of Tübingen
    German Center for Infection Research, University of Tübingen)

  • Andreas Peschel

    (Interfaculty Institute for Microbiology and Infection Medicine Tübingen (IMIT), University of Tübingen
    German Center for Infection Research, University of Tübingen)

Abstract

Sepsis caused by Gram-positive bacterial pathogens is a major fatal disease but its molecular basis remains elusive. Toll-like receptor 2 (TLR2) has been implicated in the orchestration of inflammation and sepsis but its role appears to vary for different pathogen species and clones. Accordingly, Staphylococcus aureus clinical isolates differ substantially in their capacity to activate TLR2. Here we show that strong TLR2 stimulation depends on high-level production of phenol-soluble modulin (PSM) peptides in response to the global virulence activator Agr. PSMs are required for mobilizing lipoproteins, the TLR2 agonists, from the staphylococcal cytoplasmic membrane. Notably, the course of sepsis caused by PSM-deficient S. aureus is similar in wild-type and TLR2-deficient mice, but TLR2 is required for protection of mice against PSM-producing S. aureus. Thus, a crucial role of TLR2 depends on agonist release by bacterial surfactants. Modulation of this process may lead to new therapeutic strategies against Gram-positive infections.

Suggested Citation

  • Dennis Hanzelmann & Hwang-Soo Joo & Mirita Franz-Wachtel & Tobias Hertlein & Stefan Stevanovic & Boris Macek & Christiane Wolz & Friedrich Götz & Michael Otto & Dorothee Kretschmer & Andreas Peschel, 2016. "Toll-like receptor 2 activation depends on lipopeptide shedding by bacterial surfactants," Nature Communications, Nature, vol. 7(1), pages 1-11, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12304
    DOI: 10.1038/ncomms12304
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    Cited by:

    1. Zachary Roy & Prabakar Arumugam & Blake P. Bertrand & Dhananjay D. Shinde & Vinai C. Thomas & Tammy Kielian, 2024. "Tissue niche influences immune and metabolic profiles to Staphylococcus aureus biofilm infection," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    2. Xuhui Zheng & Gerben Marsman & Keenan A. Lacey & Jessica R. Chapman & Christian Goosmann & Beatrix M. Ueberheide & Victor J. Torres, 2021. "The cell envelope of Staphylococcus aureus selectively controls the sorting of virulence factors," Nature Communications, Nature, vol. 12(1), pages 1-16, December.

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