Inhibition of staphylothrombin by dabigatran reduces Staphylococcus aureus virulence.

Area of Science:

• Microbiology
• Infectious Diseases
• Pharmacology

Background:

• Staphylocoagulase and von Willebrand binding protein (VWbp) interact with prothrombin to create the staphylothrombin complex.
• This complex facilitates the conversion of fibrinogen to fibrin, a key process in bacterial virulence.

Purpose of the Study:

• To investigate the role of staphylothrombin in Staphylococcus aureus virulence.
• To evaluate the efficacy of dabigatran in inhibiting staphylothrombin and its impact on S. aureus virulence.

Main Methods:

• Assessed the impact of staphylothrombin inhibition on S. aureus attachment to polystyrene, leukocyte activation, and bactericidal activity.
• Utilized S. aureus strains, including wild-type and mutant strains lacking staphylocoagulase and VWbp.
• Measured abscess size in mice following subcutaneous injection of S. aureus strains in animals treated with dabigatran or placebo.

Main Results:

• Staphylothrombin-mediated fibrin enhanced S. aureus adherence to surfaces and impaired leukocyte bactericidal activity.
• Inhibition or absence of staphylothrombin led to reduced bacterial attachment, improved leukocyte activation, and decreased bacterial survival in vitro.
• Dabigatran treatment or infection with coagulase-negative mutants resulted in smaller abscesses in mice.

Conclusions:

• Staphylothrombin plays a significant role in Staphylococcus aureus virulence.
• Inhibiting or eliminating staphylothrombin effectively reduces S. aureus virulence in both in vitro and in vivo experimental models.