Fibrin formation by staphylothrombin facilitates Staphylococcus aureus-induced platelet aggregation.

Area of Science:

• Microbiology
• Hematology
• Pathogenesis of infectious diseases

Background:

• Staphylococcus aureus (S. aureus) interactions with platelets are crucial in intravascular infections, including infective endocarditis (IE).
• S. aureus secretes staphylocoagulase and von Willebrand factor-binding protein (vWbp), forming the staphylothrombin complex, which activates prothrombin.

Purpose of the Study:

• To investigate the role of staphylothrombin in S. aureus-platelet interactions.
• To determine if staphylothrombin directly activates platelets or influences bacterial adhesion.

Main Methods:

• Studied staphylothrombin's effect on human platelet activation and aggregation.
• Investigated the impact of genetic absence and pharmacological inhibition of staphylothrombin on S. aureus-platelet interactions.
• Assessed bacterial trapping under high shear stress conditions.

Main Results:

• Staphylothrombin did not directly activate platelets but induced fibrinogen conversion to fibrin, promoting platelet aggregation and S. aureus-platelet interactions.
• Inhibition of staphylothrombin increased aggregation lag time and reduced bacterial trapping.
• Combined inhibition of staphylothrombin and immunoglobulin binding abolished platelet aggregation by S. aureus.

Conclusions:

• Staphylothrombin facilitates S. aureus-platelet interactions indirectly through fibrin formation, not direct platelet activation.
• Inhibiting staphylothrombin can reduce platelet activation and bacterial adhesion in S. aureus infections.
• Targeting staphylothrombin presents a potential therapeutic strategy for managing S. aureus-mediated intravascular infections.