The role of coagulases in invasive Staphylococcus aureus infections

Activation of prothrombin, fibrin generation, and platelet and leukocyte recruitment link the host’s hemostatic machinery with the immune system. Although thrombin activation and fibrin deposition can be beneficial to prevent bacterial spreading, there is increasing evidence that bacteria can also exploit these mechanisms to their benefit. S. aureus directly interacts with the host coagulation system, activating prothrombin and bypassing physiological regulation. We have shown that thrombin generation triggered by S. aureus plays a role in bacterial virulence, and various strategies aimed at inhibition of coagulase activity have proven to moderate morbidity and mortality in various models.Our work has shown that staphylothrombin generation and secondary fibrin formation increases bacterial adhesion to foreign bodies, a typical feature of S. aureus infections. This fibrin conceals the pathogen from both the immune system and antimicrobial drugs, leading to reduced bacterial killing. Fibrin formation by S. aureus further facilitated the recruitment of and interaction with human platelets under high shear stress, an important pathophysiological aspect of complicated sepsis, metastatic infections, and infective endocarditis. Animal studies confirmed the role of staphylothrombin in local and intravascular infection models, and showed an attractive potential for staphylothrombin inhibition as an additive treatment to antibiotic therapy in these conditions.Based on this promising preclinical work, a clinical trial has recently been initiated to validate these findings in patients with S. aureus bacteremia.status: publishe