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Wall teichoic acids mediate increased virulence in Staphylococcus aureus

Nature Microbiology volume 2, Article number: 16257 (2017) Cite this article

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A Corrigendum to this article was published on 13 March 2017

Abstract

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) are the cause of a severe pandemic consisting primarily of skin and soft tissue infections. The underlying pathomechanisms have not been fully understood and we report here a mechanism that plays an important role for the elevated virulence of CA-MRSA. Surprisingly, skin abscess induction in an animal model was correlated with the amount of a major cell wall component of S. aureus, termed wall teichoic acid (WTA). CA-MRSA exhibited increased cell-wall-associated WTA content (WTAhigh) and thus were more active in inducing abscess formation via a WTA-dependent and T-cell-mediated mechanism than S. aureus strains with a WTAlow phenotype. We show here that WTA is directly involved in S. aureus strain-specific virulence and provide insight into the underlying molecular mechanisms that could guide the development of novel anti-infective strategies.

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Figure 1: Amounts of WTA in the cell wall fractions of S. aureus strains and transcriptional analysis by qRT–PCR.
Figure 2: Agr-dependent control of WTA content in the staphylococcal cell wall.
Figure 3: Rot controls tarH expression and WTA biosynthesis downstream of RNAIII.
Figure 4: MHC II-dependent cytokine secretion of WTA-stimulated T cells during skin abscess formation.
Figure 5: Induction of T-cell-dependent IFN-γ secretion and abscess formation by cell wall fractions.
Figure 6: Skin abscess formation with whole bacterial cells and model for WTA-mediated strain-specific virulence.

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Acknowledgements

The authors thank I. Autenrieth and A. Peschel for discussions and critical reading of the manuscript. This research was supported by grants from the German Research Foundation (SFB) to C.We. (SFB766 and TR34), C.Wo. (SFB766 and TR34) and B.M.B. (TR34). The funders had no role in the design of the experiments, in the collection, analysis and interpretation of the data, in writing the manuscript, or in the decision to submit the manuscript for publication.

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  1. Stefanie Wanner and Jessica Schade: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Medicine, Interfacultary Institute for Microbiology and Infection Medicine (IMIT), University of Tübingen, Elfriede-Aulhorn Straße 6, 72076 Tübingen, Germany

    Stefanie Wanner, Jessica Schade, Daniela Keinhörster, Nicola Weller, Shilpa E. George, Larissa Kull, Jochen Bauer, Timo Grau, Henriette Stoy, Dorothee Kretschmer, Christiane Wolz & Christopher Weidenmaier

  2. Department of Microbiology, University of Chicago, Chicago, 60637, Illinois, USA

    Volker Winstel

  3. Medical Microbiology, UMC Utrecht, Heidelberglaan 100, 3584CX Utrecht, The Netherlands

    Julia Kolata

  4. Department of Immunology, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße DZ7, 17475 Greifswald, Germany

    Barbara M. Bröker

  5. German Center for Infection Research (DZIF), Partner Site Tübingen, 72076 Tübingen, Germany

    Christopher Weidenmaier

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Contributions

S.W., C.Wo., J.K., B.M.B., J.S. and C.We. planned the experiments. S.W., J.S., N.W., D.Ke., L.K., J.B., T.G., V.W. and C.We. performed the experiments. C.Wo., J.K., B.M.B., V.W. and D.Kr. supplied materials and strains. S.W., J.S. and C.We. wrote the manuscript. All authors read and approved the final manuscript.

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Correspondence to Christopher Weidenmaier.

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Wanner, S., Schade, J., Keinhörster, D. et al. Wall teichoic acids mediate increased virulence in Staphylococcus aureus. Nat Microbiol 2, 16257 (2017). https://doi.org/10.1038/nmicrobiol.2016.257

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