Staphylococcus aureus-induced clotting of plasma is an immune evasion mechanism for persistence within the fibrin network

Abstract

Recent work has shown that coagulation and innate immunity are tightly interwoven host responses that help eradicate an invading pathogen. Some bacterial species, including Staphylococcus aureus, secrete pro-coagulant factors that, in turn, can modulate these immune reactions. Such mechanisms may not only protect the micro-organism from a lethal attack, but also promote bacterial proliferation and the establishment of infection. Our data showed that coagulase-positive S. aureus bacteria promoted clotting of plasma which was not seen when a coagulase-deficient mutant strain was used. Furthermore, in vitro studies showed that this ability constituted a mechanism that supported the aggregation, survival and persistence of the microorganism within the fibrin network. These findings were also confirmed when agglutination and persistence of coagulase-positive S. aureus bacteria at the local focus of infection were studied in a subcutaneous murine infection model. In contrast, the coagulase-deficient S. aureus strain which was not able to induce clotting failed to aggregate and to persist in vivo. In conclusion, our data suggested that coagulase-positive S. aureus have evolved mechanisms that prevent their elimination within a fibrin clot.

Non-canonical proteolytic activation of human prothrombin by subtilisin from Bacillus subtilis may shift the procoagulant–anticoagulant equilibrium toward thrombosis

“…Very recently, fibrin generation has been proposed as a host defense mechanism of innate immunity to avoid systemic activation of coagulation by segregating bacterial pathogens in a fibrin network at infection sites (66). However, activation of coagulation can also be seen as a smart evolutionary mechanism, whereby the pathogens exploit the host hemostatic system components to escape immune response and prevent their elimination from the blood by "self-entrapment" within a fibrin clot (67). Beyond these intriguing host-pathogen evolutionary Non-canonical proteolytic activation of prothrombin strategies, the pathological activation of coagulation in infectious diseases is associated with high morbidity and mortality (22,68).…”

Molecular Interactions of Human Plasminogen with Fibronectin-binding Protein B (FnBPB), a Fibrinogen/Fibronectin-binding Protein from Staphylococcus aureus

“…For example, degradation of host-or SAK-promoted fibrin clots could help bacteria to spread (37). Damage to subcutaneous tissue could contribute to the pathogenesis of skin soft tissue infections caused by CA-MRSA (38).…”

Tissue Plasminogen Activator Coating on Implant Surfaces Reduces Staphylococcus aureus Biofilm Formation

“…Unfortunately, fibrin-rich S. aureus biofilms appear rapidly, which might decrease the efficacy of antibiotic prophylaxis (30) and blunt phagocytosis (9,11,31,32). Importantly, tPA coating prevents the first step of biofilm formation, the adhesion of S. aureus to the implant surface, thereby expanding the window of opportunity and allowing more efficient pathogen clearance.…”