Toxins 2011, 3(2), 120-133; doi:10.3390/toxins3020120
Article

Staphylococcus aureus α-Toxin Triggers the Synthesis of B-Cell Lymphoma 3 by Human Platelets

Sebastian Schubert 1 email, Hansjörg Schwertz 2 email, Andrew S. Weyrich 2 email, Zechariah G. Franks 2 email, Stephan Lindemann 3 email, Monika Otto 1 email, Hagen Behr 1 email, Harald Loppnow 1 email, Axel Schlitt 1 email, Martin Russ 1 email, Peter Presek 4 email, Karl Werdan 1 email and Michael Buerke 1,* email
1 Department of Medicine III, Martin Luther University, Halle, Saale, Germany 2 Program in Molecular Medicine, University of Utah, Salt Lake City, UT 84112, USA 3 Department of Medicine III, Eberhard Karls University, Tübingen, Germany 4 Clinical Pharmacology, Martin Luther University, Halle, Saale, Germany
* Author to whom correspondence should be addressed.
Received: 23 December 2010; in revised form: 22 January 2011 / Accepted: 25 January 2011 / Published: 28 January 2011
PDF Full-text Download PDF Full-Text [673 KB, uploaded 28 January 2011 12:47 CET]
Abstract: The frequency and severity of bacteremic infections has increased over the last decade and bacterial endovascular infections (i.e., sepsis or endocarditis) are associated with high morbidity and mortality. Bacteria or secreted bacterial products modulate platelet function and, as a result, affect platelet accumulation at sites of vascular infection and inflammation. However, whether bacterial products regulate synthetic events in platelets is not known. In the present study, we determined if prolonged contact with staphylococcal α-toxin signals platelets to synthesize B-cell lymphoma (Bcl-3), a protein that regulates clot retraction in murine and human platelets. We show that α-toxin induced αIIbβ3-dependent aggregation (EC50 2.98 µg/mL ± 0.64 µg/mL) and, over time, significantly altered platelet morphology and stimulated de novo accumulation of Bcl-3 protein in platelets. Adherence to collagen or fibrinogen also increased the expression of Bcl-3 protein by platelets. α-toxin altered Bcl-3 protein expression patterns in platelets adherent to collagen, but not fibrinogen. Pretreatment of platelets with inhibitors of protein synthesis or the mammalian Target of Rapamycin (mTOR) decreased Bcl-3 protein expression in α-toxin stimulated platelets. In conclusion, Staphylococcus aureus-derived α-toxin, a pore forming exotoxin, exerts immediate (i.e., aggregation) and prolonged (i.e., protein synthesis) responses in platelets, which may contribute to increased thrombotic events associated with gram-positive sepsis or endocarditis.
Keywords: α-toxin; Bcl-3; protein synthesis

Article Statistics

Click here to load and display the download statistics.

Cite This Article

MDPI and ACS Style

Schubert, S.; Schwertz, H.; Weyrich, A.S.; Franks, Z.G.; Lindemann, S.; Otto, M.; Behr, H.; Loppnow, H.; Schlitt, A.; Russ, M.; Presek, P.; Werdan, K.; Buerke, M. Staphylococcus aureus α-Toxin Triggers the Synthesis of B-Cell Lymphoma 3 by Human Platelets. Toxins 2011, 3, 120-133.

AMA Style

Schubert S, Schwertz H, Weyrich AS, Franks ZG, Lindemann S, Otto M, Behr H, Loppnow H, Schlitt A, Russ M, Presek P, Werdan K, Buerke M. Staphylococcus aureus α-Toxin Triggers the Synthesis of B-Cell Lymphoma 3 by Human Platelets. Toxins. 2011; 3(2):120-133.

Chicago/Turabian Style

Schubert, Sebastian; Schwertz, Hansjörg; Weyrich, Andrew S.; Franks, Zechariah G.; Lindemann, Stephan; Otto, Monika; Behr, Hagen; Loppnow, Harald; Schlitt, Axel; Russ, Martin; Presek, Peter; Werdan, Karl; Buerke, Michael. 2011. "Staphylococcus aureus α-Toxin Triggers the Synthesis of B-Cell Lymphoma 3 by Human Platelets." Toxins 3, no. 2: 120-133.

Toxins EISSN 2072-6651 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert