Background
Physiology of thrombin generation
Pathophysiology of thrombin and fibrin formation during infection
Initiation: the emerging role of contact activation system (Fig. 1)
Physiology or pathophysiology?
Polyphosphates (polyP)
Neutrophil extracellular traps (NETs)
Pathogen-induced modulation of blood coagulation (Table 1)
Initiation of coagulation
Bacteria | Protein | Target | Result | References |
---|---|---|---|---|
A—initiation of coagulation
| ||||
All bacteria | PolyP | FXII → FXIIa | Contact phase activation (FXI) | [51] |
S. aureus
| Coagulase | FII → FIIa | Non-proteolytic activation | [52] |
von Willebrand binding protein (vWbp) | vWF (endothelium) |
S. aureus anchorage to endothelium | [53] | |
FII → FIIa | Non-proteolytic activation | [52] | ||
vWbp-FIIa → FXIII | Clot stabilisation | [53] | ||
Clumping factor A (ClfA) and fibronectin-binding protein A (FnbpA) | Fg |
S. aureus—platelet bridging and clot formation | [54] | |
Staphopains A and B (ScpA, ScpB) | HK → BK | Vascular leakage | ||
Group G streptococci
| Fibrinogen-binding protein (FOG) and protein G (PG) | FXII → FXIIa | Contact phase complex assembly and activation (FXI) at bacterial surface | [57] |
B. anthracis
| Zinc metalloprotease InhA1 | FX → FXa/FII → FIIa | Fibrin deposition | |
ADAMTS13 inhibition | Platelet adhesion/activation by UL-vWF | [58] | ||
B—degradation of fibrin clot
| ||||
B. burgdorferi
| Outer surface proteins (OspA and OspC) and Erp proteins (ErpA, ErpC and ErpP) | Plasmin(ogen) | Plasminogen activation by tPA/uPA | [62] |
H. influenzae
| Surface protein E (PE) | Plasmin(ogen) | Plasminogen activation by tPA/uPA | [63] |
Streptococci spp.
| α-Enolase | Plasmin(ogen) | Plasminogen activation by tPA/uPA | |
B. anthracis
| α-Enolase and elongation factor tu | Plasmin(ogen) | Plasminogen activation by tPA/uPA | [66] |
S. pyogenes
| Plasminogen-binding M-like protein (PAM) and streptokinase (SK) | Plasminogen | Direct non-enzymatic activation | [51] |
Metalloprotease activation and tissue invasion by PAM-bound SK·PM | ||||
S. agalactiae
| Skizzle (SkzL) | tPA/uPA | Enhanced plasminogen activation | [70] |
Y. pestis
| Omptin Pla | Plasminogen | Direct activation in presence of LPS | [71] |
PAI-1/TAFI/α2-AP | Inactivation of serpins | |||
S. enterica
| Omptin PgtE | PAI-1/α2-AP | Inactivation of serpins | [76] |
C—inactivation of fibrinolysis
| ||||
Group A streptococci
| Collagen-like proteins (SclA and SclB) | TAFI and FIIa | TAFI → TAFIa | |
D—Inhibition of coagulation
| ||||
Group A streptococci
| Streptococcal inhibitor of complement (SIC) | HK | Inhibition of HK binding and contact phase activation | |
S. aureus
| Staphylococcal superantigen-like protein 10 (SSLP-10) | FII | Inhibition of platelet binding and activation | [81] |