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- Title
The Role of Staphylothrombin-Mediated Fibrin Deposition in Catheter-Related Staphylococcus aureus Infections.
- Authors
Vanassche, Thomas; Peetermans, Marijke; Van Aelst, Lucas N. L.; Peetermans, Willy E.; Verhaegen, Jan; Missiakas, Dominique M.; Schneewind, Olaf; Hoylaerts, Marc F.; Verhamme, Peter
- Abstract
Staphylococcus aureus (S. aureus) is a frequent cause of catheter-related infections. S. aureus secretes the coagulases staphylocoagulase and von Willebrand factor–binding protein, both of which form a staphylothrombin complex upon binding to prothrombin. Although fibrinogen and fibrin facilitate the adhesion of S. aureus to catheters, the contribution of staphylothrombin-mediated fibrin has not been examined. In this study, we use a S. aureus mutant lacking both coagulases (Δcoa/vwb) and dabigatran, a pharmacological inhibitor of both staphylothrombin and thrombin, to address this question. Genetic absence or chemical inhibition of pathogen-driven coagulation reduced both fibrin deposition and the retention of S. aureus on catheters in vitro. In a mouse model of jugular vein catheter infection, dabigatran reduced bacterial load on jugular vein catheters, as well as metastatic kidney infection. Importantly, inhibition of staphylothrombin improved the efficacy of vancomycin treatment both in vitro and in the mouse model.
- Subjects
STAPHYLOCOCCUS aureus infections; THROMBIN; FIBRIN; CATHETER-related infections; IN vitro studies; METASTASIS
- Publication
Journal of Infectious Diseases, 2013, Vol 208, Issue 1, p92
- ISSN
0022-1899
- Publication type
Article
- DOI
10.1093/infdis/jit130