title: Inhibition of staphylothrombin by dabigatran reduces Staphylococcus aureus virulence.
abstract: BACKGROUND
  Staphylocoagulase and von Willebrand binding protein (VWbp) bind to prothrombin to form the staphylothrombin complex that converts fibrinogen into fibrin.
  
  
  OBJECTIVE
  To study the role of staphylothrombin and its inhibition by dabigatran on Staphylococcus aureus virulence.
  
  
  METHODS
  We studied the effect of staphylothrombin inhibition on bacterial attachment to polystyrene surfaces, leukocyte activation and bactericidal activity for S. aureus ATCC 25923, S. aureus Newman, and staphylocoagulase- and VWbp-negative S. aureus Newman mutants in the presence or absence of prothrombin and fibrinogen. We measured the abscess size after subcutaneous (s.c.) injection of S. aureus ATCC 25923 and S. aureus Newman, as well as an S. aureus Newman mutant strain lacking staphylocoagulase and VWbp, in mice treated with either dabigatran or placebo.
  
  
  RESULTS
  Staphylothrombin-mediated fibrin increased the association of S. aureus to polystyrene surfaces and reduced the bactericidal activity of leukocytes. The absence or inhibition of staphylothrombin decreased the bacterial association, enhanced leukocyte activation and reduced bacterial survival in vitro. Abscess size was smaller in mice treated with dabigatran or infected with a coagulase-negative mutant.
  
  
  CONCLUSIONS
  Inhibition or the absence of staphylothrombin reduced S. aureus virulence in in vitro and in vivo models.
authors: Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium. thomas.vanassche@med.kuleuven.be
authors: T
authors: T
authors: Vanassche
authors: J
authors: J
authors: Verhaegen
authors: W E
authors: WE
authors: Peetermans
authors: J
authors: J
authors: VAN Ryn
authors: A
authors: A
authors: Cheng
authors: O
authors: O
authors: Schneewind
authors: M F
authors: MF
authors: Hoylaerts
authors: P
authors: P
authors: Verhamme
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion / Q000187:drug effects; D001562:Benzimidazoles / Q000494:pharmacology*; D000069604:Dabigatran; D004797:Enzyme-Linked Immunosorbent Assay; D005340:Fibrinogen / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D010919:Placebos; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000472:pathogenicity; D013917:Thrombin / Q000037:antagonists & inhibitors*; D014774:Virulence / Q000187:drug effects*; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D001562:Benzimidazoles; D010919:Placebos; D015091:beta-Alanine; D005340:Fibrinogen; D013917:Thrombin; C022654:staphylothrombin; D000069604:Dabigatran