Contribution of Coagulases towards Staphylococcus aureus Disease and Protective Immunity

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Abstract
The bacterial pathogen Staphylococcus aureus seeds abscesses in host tissues to replicate at the center of these lesions, protected from host immune cells via a pseudocapsule. Using histochemical staining, we identified prothrombin and fibrin within abscesses and pseudocapsules. S. aureus secretes two clotting factors, coagulase (Coa) and von Willebrand factor binding protein (vWbp). We report here that Coa and vWbp together are required for the formation of abscesses. Coa and vWbp promote the non-proteolytic activation of prothrombin and cleavage of fibrinogen, reactions that are inhibited with specific antibody against each of these molecules. Coa and vWbp specific antibodies confer protection against abscess formation and S. aureus lethal bacteremia, suggesting that coagulases function as protective antigens for a staphylococcal vaccine. Clinical isolates of the human pathogen Staphylococcus aureus secrete coagulase (Coa), a polypeptide that binds to and activates prothrombin, thereby converting fibrinogen to fibrin and promoting clotting of plasma or blood. Another secreted coagulase, designated von-Willebrand factor binding protein (vWbp), catalyzes a similar reaction. Staphylococcal binding to fibrinogen or fibrin is an important attribute of disease pathogenesis, which leads to the formation of abscesses and bacterial persistence in host tissues. We report here that Coa and vWbp are essential for S. aureus strain Newman abscess formation and persistence in host tissues. Antibodies directed against Coa or vWbp prevent coagulase binding to prothrombin or fibrinogen and confer protection against challenge with S. aureus Newman or the methicillin-resistant S. aureus isolate USA300 LAC in mouse models of abscess formation or lethal sepsis. These results suggest that coagulases may be used as vaccine antigens to elicit antibodies that protect humans against S. aureus infections.

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