Thromb Haemost 2018; 118(04): 745-757
DOI: 10.1055/s-0038-1637735
Blood Cells, Inflammation and Infection
Schattauer GmbH Stuttgart

Secreted Immunomodulatory Proteins of Staphylococcus aureus Activate Platelets and Induce Platelet Aggregation

Ulrike Binsker
1  Department of Molecular Genetics and Infection Biology, Interfaculty Institute for Genetics and Functional Genomics, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, Germany
,
Raghavendra Palankar
2  Department of Transfusion Medicine, Institute of Immunology and Transfusion Medicine, University Medicine Greifswald, Greifswald, Germany
,
Jan Wesche
2  Department of Transfusion Medicine, Institute of Immunology and Transfusion Medicine, University Medicine Greifswald, Greifswald, Germany
,
Thomas P. Kohler
1  Department of Molecular Genetics and Infection Biology, Interfaculty Institute for Genetics and Functional Genomics, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, Germany
,
Josephine Prucha
1  Department of Molecular Genetics and Infection Biology, Interfaculty Institute for Genetics and Functional Genomics, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, Germany
,
Gerhard Burchhardt
1  Department of Molecular Genetics and Infection Biology, Interfaculty Institute for Genetics and Functional Genomics, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, Germany
,
Manfred Rohde
3  Central Facility for Microscopy, ZEIM, Helmholtz Centre for Infection Research, Braunschweig, Germany
,
Frank Schmidt
4  Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, Center for Functional Genomics of Microbes, University Medicine Greifswald, Greifswald, Germany
,
Barbara M. Bröker
5  Department of Immunology, Institute of Immunology and Transfusion Medicine, University Medicine Greifswald, Greifswald, Germany
,
Uwe Mamat
6  Division of Cellular Microbiology, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Borstel, Germany
,
Jan Pané-Farré
7  Department of Microbial Physiology and Molecular Biology, Institute for Microbiology, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, Germany
,
Anica Graf
7  Department of Microbial Physiology and Molecular Biology, Institute for Microbiology, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, Germany
,
Patrick Ebner
8  Department of Microbial Genetics, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany
,
Andreas Greinacher
2  Department of Transfusion Medicine, Institute of Immunology and Transfusion Medicine, University Medicine Greifswald, Greifswald, Germany
,
Sven Hammerschmidt
1  Department of Molecular Genetics and Infection Biology, Interfaculty Institute for Genetics and Functional Genomics, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, Germany
› Author Affiliations
Funding This work was supported by a grant from the Deutsche Forschungsgemeinschaft (SFB/TRR34 project C10 to S.H. and A.G., project C4 to B.M.B.). The work was also partially supported by the BMBF/“Unternehmen Region” as part of the ZIK-FunGene.
Further Information

Publication History

05 October 2017

30 January 2018

Publication Date:
19 March 2018 (eFirst)

Abstract

Staphylococcus aureus can cause bloodstream infections associated with infective endocarditis (IE) and disseminated intravascular coagulopathy (DIC). Both complications involve platelets. In view of an increasing number of antibiotic-resistant strains, new approaches to control systemic S. aureus infection are gaining importance. Using a repertoire of 52 recombinant S. aureus proteins in flow cytometry-based platelet activation and aggregation assays, we identified, in addition to the extracellular adherence protein Eap, three secreted staphylococcal proteins as novel platelet activating proteins. Eap and the chemotaxis inhibitory protein of S. aureus (CHIPS), the formyl peptide receptor-like 1 inhibitory protein (FLIPr) and the major autolysin Atl induced P-selectin expression in washed platelets and platelet-rich plasma. Similarly, AtlA, CHIPS and Eap induced platelet aggregation in whole blood. Fluorescence microscopy illustrated that P-selectin expression is associated with calcium mobilization and re-organization of the platelet actin cytoskeleton. Characterization of the functionally active domains of the major autolysin AtlA and Eap indicates that the amidase domain of Atl and the tandem repeats 3 and 4 of Eap are crucial for platelet activation. These results provide new insights in S. aureus protein interactions with platelets and identify secreted proteins as potential treatment targets in case of antibiotic-resistant S. aureus infection.

Supplementary Material