title: Staphylococcus aureus α-toxin triggers the synthesis of B-cell lymphoma 3 by human platelets.
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 α(IIb)β(3)-dependent aggregation (EC(50) 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, Staphylococcusaureus-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.
authors: Department of Medicine III, Martin Luther University, Halle, Saale, Germany. schubert-sebastian@gmx.net
authors: Sebastian
authors: S
authors: Schubert
authors: Hansjörg
authors: H
authors: Schwertz
authors: Andrew S
authors: AS
authors: Weyrich
authors: Zechariah G
authors: ZG
authors: Franks
authors: Stephan
authors: S
authors: Lindemann
authors: Monika
authors: M
authors: Otto
authors: Hagen
authors: H
authors: Behr
authors: Harald
authors: H
authors: Loppnow
authors: Axel
authors: A
authors: Schlitt
authors: Martin
authors: M
authors: Russ
authors: Peter
authors: P
authors: Presek
authors: Karl
authors: K
authors: Werdan
authors: Michael
authors: M
authors: Buerke
mesh_terms: D000081242:B-Cell Lymphoma 3 Protein; D001427:Bacterial Toxins / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry; D005340:Fibrinogen / Q000737:chemistry; D006460:Hemolysin Proteins / Q000494:pharmacology*; D006801:Humans; D015539:Platelet Activation / Q000187:drug effects*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D013211:Staphylococcus aureus; D014157:Transcription Factors / Q000096:biosynthesis*
chemical_list: D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; C021091:staphylococcal alpha-toxin; D005340:Fibrinogen; D003094:Collagen