Bacteria-derived factors that modulate coagulation, fibrinolysis, and complement systems of the host
| Bacterial factor . | Bacteria species . | Host target . | Host effect . |
|---|---|---|---|
| Staphylokinase | Staphylococcus | Plasminogen | Activation of fibrinolysis |
| Staphylocoagulase | Staphylococcus | Prothrombin | Activation of coagulation via a nonproteolytic conformational change of prothrombin |
| Clumping factors A and B (CLFA, CLFB) | Staphylococcus | Fibrinogen and platelets | Impairs pathogen clearance |
| Extracellular fibrinogen binding (Efb) protein | Staphylococcus | Fibrinogen, C3 | Inhibits platelet aggregation, neutrophil binding to fibrinogen and complement-mediated opsonization and phagocytosis |
| Staphylococcal superantigen-like protein 10 (SSL10) | Staphylococcus | Vitamin K–dependent clotting factors | Inhibits blood coagulation by targeting Gla domains of clotting factors |
| Streptokinase | Streptococcus | Plasminogen | Activation of fibrinolysis |
| Streptococcal inhibitor of complement (SIC) | Streptococcus | HK | Inhibits complement and contact phase activation |
| Surface collagen-like (Scl) proteins A and B | Group A Streptococcus | TAFI, thrombin and plasmin | Promotes TAFI activation resulting in inhibition of fibrinolysis |
| Omptins | G− bacteria (E coli, Salmonella and Yersinia) | TFPI | Inhibit TFPI-mediated anticoagulation |
| Phospholipases | Multiple bacteria species | GPI-anchored proteins | Cleaves cell surface–associated, GPI-anchored proteins (TFPI, uPAR, CD55, and CD59), thus decreasing anticoagulant, profibrinolytic, and anti-complement functions |
| Glycosidases (hyaluronidases, sialidases, heparinases, chrondroitinases) | Multiple bacteria species | Hyaluronans, sialic acid, heparin/heparan sulfate, and chondroitin sulfate residues | Degradation of the glycocalyx leading to decreased anticoagulant activity and impaired cytoprotection against histone-induced toxicity |
| DNAse | Multiple bacterial species | NETs, cell-free DNA | Degradation of prothrombotic DNA and NETs |
| Polyphosphates | Multiple bacterial species | FXII | Trigger activation of contact pathway |
| LPS | G− bacteria | CD14-TLR4 signaling; complement and contact pathway | Triggers production of proinflammatory cytokines, TF, and PAI-1 and activation of contact and alternative complement pathways |
| Peptidoglycan | G+ bacteria | FcR, NOD and inflammasome signaling; complement and contact activation pathways; inhibits antithrombin | Induces expression of cytokines and TF and the activation of complement and contact pathways |
| Bacterial factor . | Bacteria species . | Host target . | Host effect . |
|---|---|---|---|
| Staphylokinase | Staphylococcus | Plasminogen | Activation of fibrinolysis |
| Staphylocoagulase | Staphylococcus | Prothrombin | Activation of coagulation via a nonproteolytic conformational change of prothrombin |
| Clumping factors A and B (CLFA, CLFB) | Staphylococcus | Fibrinogen and platelets | Impairs pathogen clearance |
| Extracellular fibrinogen binding (Efb) protein | Staphylococcus | Fibrinogen, C3 | Inhibits platelet aggregation, neutrophil binding to fibrinogen and complement-mediated opsonization and phagocytosis |
| Staphylococcal superantigen-like protein 10 (SSL10) | Staphylococcus | Vitamin K–dependent clotting factors | Inhibits blood coagulation by targeting Gla domains of clotting factors |
| Streptokinase | Streptococcus | Plasminogen | Activation of fibrinolysis |
| Streptococcal inhibitor of complement (SIC) | Streptococcus | HK | Inhibits complement and contact phase activation |
| Surface collagen-like (Scl) proteins A and B | Group A Streptococcus | TAFI, thrombin and plasmin | Promotes TAFI activation resulting in inhibition of fibrinolysis |
| Omptins | G− bacteria (E coli, Salmonella and Yersinia) | TFPI | Inhibit TFPI-mediated anticoagulation |
| Phospholipases | Multiple bacteria species | GPI-anchored proteins | Cleaves cell surface–associated, GPI-anchored proteins (TFPI, uPAR, CD55, and CD59), thus decreasing anticoagulant, profibrinolytic, and anti-complement functions |
| Glycosidases (hyaluronidases, sialidases, heparinases, chrondroitinases) | Multiple bacteria species | Hyaluronans, sialic acid, heparin/heparan sulfate, and chondroitin sulfate residues | Degradation of the glycocalyx leading to decreased anticoagulant activity and impaired cytoprotection against histone-induced toxicity |
| DNAse | Multiple bacterial species | NETs, cell-free DNA | Degradation of prothrombotic DNA and NETs |
| Polyphosphates | Multiple bacterial species | FXII | Trigger activation of contact pathway |
| LPS | G− bacteria | CD14-TLR4 signaling; complement and contact pathway | Triggers production of proinflammatory cytokines, TF, and PAI-1 and activation of contact and alternative complement pathways |
| Peptidoglycan | G+ bacteria | FcR, NOD and inflammasome signaling; complement and contact activation pathways; inhibits antithrombin | Induces expression of cytokines and TF and the activation of complement and contact pathways |