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

Ulrike Binsker; Raghavendra Palankar; Jan Wesche; Thomas P. Kohler; Josephine Prucha; Gerhard Burchhardt; Manfred Rohde; Frank Schmidt; Barbara M. Bröker; Uwe Mamat; Jan Pané-Farré; Anica Graf; Patrick Ebner; Andreas Greinacher; Sven Hammerschmidt

doi:10.1055/s-0038-1637735

Thrombosis and Haemostasis, Table of Contents

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

Authors

Ulrike Binsker

¹Department 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

²Department of Transfusion Medicine, Institute of Immunology and Transfusion Medicine, University Medicine Greifswald, Greifswald, Germany
Jan Wesche

²Department of Transfusion Medicine, Institute of Immunology and Transfusion Medicine, University Medicine Greifswald, Greifswald, Germany
Thomas P. Kohler

¹Department 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

¹Department 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

¹Department 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

³Central Facility for Microscopy, ZEIM, Helmholtz Centre for Infection Research, Braunschweig, Germany
Frank Schmidt

⁴Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, Center for Functional Genomics of Microbes, University Medicine Greifswald, Greifswald, Germany
Barbara M. Bröker

⁵Department of Immunology, Institute of Immunology and Transfusion Medicine, University Medicine Greifswald, Greifswald, Germany
Uwe Mamat

⁶Division of Cellular Microbiology, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Borstel, Germany
Jan Pané-Farré

⁷Department of Microbial Physiology and Molecular Biology, Institute for Microbiology, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, Germany
Anica Graf

⁷Department of Microbial Physiology and Molecular Biology, Institute for Microbiology, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, Germany
Patrick Ebner

⁸Department of Microbial Genetics, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany
Andreas Greinacher

²Department of Transfusion Medicine, Institute of Immunology and Transfusion Medicine, University Medicine Greifswald, Greifswald, Germany
Sven Hammerschmidt

¹Department of Molecular Genetics and Infection Biology, Interfaculty Institute for Genetics and Functional Genomics, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, Germany

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.

Keywords

blood platelets - Staphylococcus aureus - platelet activation - platelet aggregation - immunomodulatory

Full Text

References

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