<i>Staphylococcus aureus</i> Secretes Coagulase and von Willebrand Factor Binding Protein to Modify the Coagulation Cascade and Establish Host Infections

Abstract

Clinical isolates of Staphylococcus aureus secrete coagulases, polypeptides that bind to and activate prothrombin, thereby converting fibrinogen to fibrin and promoting the clotting of plasma or blood. Two staphylococcal products, the canonical coagulase (Coa) as well as the recently identified von Willebrand factor binding protein (vWbp), promote similar modifications of the coagulation cascade during host infection. 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 and also enables the pathogen to cause lethal sepsis. Circumstantial evidence suggests that the product of coagulase activity, staphylococci captured within a fibrin meshwork, enable this pathogen to disseminate as thromboembolic lesions and to resist opsonophagocytic clearance by host immune cells. In addition, the coagulation products of staphylococci appear to display discrete differences when compared to those of thrombin-mediated coagulation, the latter representing a key innate defense mechanism against many invading pathogens. Preclinical evidence suggests that inactivation or neutralization of coagulases may prevent the pathogenesis of staphylococcal infections, a strategy that could be used to combat the current epidemic of hospital-acquired infections with drug-resistant S. aureus isolates.

N-Acetylglucosaminylation of Serine-Aspartate Repeat Proteins Promotes Staphylococcus aureus Bloodstream Infection

“…This Gram-positive bacterium evolved to clot animal and human plasma, bind fibrinogen, and agglutinate within a meshwork of fibrin fibrils (3). S. aureus agglutination requires two secreted products, Coa (coagulase) and vWbp (von Willebrand factor-binding protein) (4), which each associate with and activate prothrombin to convert fibrinogen to fibrin (5,6).…”

Staphylococcal Superantigen-like Protein 10 (SSL10) Inhibits Blood Coagulation by Binding to Prothrombin and Factor Xa via Their γ-Carboxyglutamic Acid (Gla) Domain

“…staphylothrombin (21). Coagulase is thought to be responsible for the virulence of S. aureus (22). SSL10 did not inhibit the proteolytic activity of staphylothrombin, mildly attenuated the formation of staphylothrombin, and inhibited plasma clotting induced by coagulase.…”

Surveillance and Countermeasures in Innate Immunity

“…Recently, it was shown that the S. aureus protease staphopain A degrades SP-A, thus compromising host defense of the alveoli [5]. In a recent review, the importance of staphylococcal coagulases was discussed [6]. The canonical coagulase as well as the von Willebrand factor binding protein modify the coagulation cascade during infection.…”