Staphylococcus aureus, master manipulator of the human hemostatic system

Abstract

The coagulation system does not only offer protection against bleeding, but also aids in our defense against invading microorganisms. The hemostatic system and innate immunity are strongly entangled, which explains why so many infections are complicated by either bleeding or thrombosis. Staphylococcus aureus (S. aureus), currently the most deadly infectious agent in the developed world, causes devastating intravascular infections such as sepsis and infective endocarditis. During these infections S. aureus comes in close contact with the host hemostatic system and proves to be a master in manipulating coagulation. The coagulases of S. aureus directly induce coagulation by activating prothrombin. S. aureus also manipulates fibrinolysis by triggering plasminogen activation via staphylokinase. Furthermore, S. aureus binds and activates platelets and interacts with key coagulation proteins such as fibrin(ogen), fibronectin and von Willebrand factor. By manipulating the coagulation system S. aureus gains a significant advantage over the host defense mechanisms. Studying the interplay between S. aureus and the hemostatic system can therefore lead to new innovative therapies for battling S. aureus infections.

Von Willebrand factor and ADAMTS13 impact on the outcome of Staphylococcus aureus sepsis

“…Widespread endothelial activation by inflammatory cytokines further promotes a prothrombotic state . Many bacteria also directly activate the coagulation system or exhibit specific interactions with the vascular wall …”

“…Up to one‐half of bloodstream infections are caused by Gram‐positive bacteria, with S. aureus being the second most frequently isolated single pathogen . S. aureus is highly specialized to interact with platelets, the coagulation system, fibrin, and subendothelial matrix proteins . In addition, S. aureus can also bind directly to VWF using its von Willebrand binding protein (vWbp), a feature that has been proved crucial for its adhesion to the vessel wall .…”

“…1-3 Many bacteria also directly activate the coagulation system or exhibit specific interactions with the vascular wall. 4,5 Activated endothelial cells release von Willebrand factor (VWF) from Weibel-Palade bodies. VWF forms high molecular weight multimeric molecules that remain temporarily associated with the vessel wall.…”

“…32,33 S. aureus is highly specialized to interact with platelets, the coagulation system, fibrin, and subendothelial matrix proteins. [5][6][7][34][35][36] In addition, S. aureus can also bind directly to VWF using its von Willebrand binding protein (vWbp), a feature that has been proved crucial for its adhesion to the vessel wall. 6,7,36 S. aureus can form small bacteria-platelet-fibrin microaggregates, which will stick avidly to VWF exposed on the vessel wall.…”

Plasmin inhibition by bacterial serpin: Implications in gum disease

“…5,6 Another important function of fibrin deposits is to trap bacteria to prevent their spread. 7,8 A more universal approach for hijacking the host plasmin system is to express plasmin(ogen) receptors on the bacterial cell surface, and such receptors can be either specialized proteins or glycolytic enzymes that are released to the bacterial surface. These strategies include direct activation of plasminogen via streptokinases produced by group A, C, and G streptococci, staphylokinase produced by Staphylococcus aureus, and the Pla protease expressed by Yersinia pestis.…”