Candida albicans and its metabolite gliotoxin inhibit platelet function via interaction with thiols
Anne Bertling
1
Department of Anaesthesiology and Intensive Care, Experimental and Clinical Haemostasis, University of Muenster, Muenster, Germany
4
Interdisciplinary Center of Clinical Research, University Hospital of Muenster, Muenster, Germany
,
Silke Niemann
1
Department of Anaesthesiology and Intensive Care, Experimental and Clinical Haemostasis, University of Muenster, Muenster, Germany
,
Andreas Uekötter
2
Department of Medical Microbiology, University of Muenster, Muenster, Germany
4
Interdisciplinary Center of Clinical Research, University Hospital of Muenster, Muenster, Germany
,
Wolfgang Fegeler
2
Department of Medical Microbiology, University of Muenster, Muenster, Germany
,
Cornelia Lass-Flörl
3
Innsbruck Medical University, Department of Hygiene, Microbiology, and Social Medicine, Innsbruck, Austria
,
Christof von Eiff
2
Department of Medical Microbiology, University of Muenster, Muenster, Germany
4
Interdisciplinary Center of Clinical Research, University Hospital of Muenster, Muenster, Germany
,
Beate E. Kehrel
1
Department of Anaesthesiology and Intensive Care, Experimental and Clinical Haemostasis, University of Muenster, Muenster, Germany
4
Interdisciplinary Center of Clinical Research, University Hospital of Muenster, Muenster, Germany
› Author AffiliationsFinancial support: This work was supported by a grant of the Interdisciplinary Center of Clinical Research (IZKF) Muenster (project no. Keh1/037/07).
Platelets bind to Candida albicans, the major cause of candidiasis. But in contrast to other microorganisms the fungus does not aggregate platelets. Gliotoxin (GT), which possesses immunosuppressive properties, is produced by various fungi, including the opportunistic pathogens Aspergillus fumigatus and C. albicans. Its mode of action involves the formation of mixed disulfides with host proteins. Disulfide exchanges play an important role in platelet activation. Therefore, the effect of C. albicans and GT on platelet function was tested. C. albicans yeast cells (5,000–10,000 cells/μl) and GT, in pathophysiologically relevant concentrations (0.05–0.5 μM), inhibited platelet fibrinogen binding, anti gp IIb/IIIa antibody PAC-1 binding, aggregation and procoagulant activity in a dose-dependent manner. Alpha granule release, measured via CD62P surface expression, was not affected. Addition of reduced glutathione partially counteracted the effect of C. albicans and GT on platelet fibrinogen binding and platelet aggregation. The C. albicans metabolite GT features antithrombotic properties in addition to its immunosuppressive functions. Since treatment with reduced glutathione partially counteracted the inhibitory effect of C. albicans yeast cells and GT on platelet fibrinogen binding, the antithrombotic activity is likely to depend on the disulfide bridge of this mycotoxin. GT production by C. albicans could contribute to its survival in the blood stream during vascular infections. The knowledge of the underlying mechanisms of the antithrombotic properties might help to treat fungal infections as well as thrombosis.
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