title: The role of staphylothrombin-mediated fibrin deposition in catheter-related Staphylococcus aureus infections.
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.
authors.affiliation: Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, University of Leuven, Herestraat 49, B-3000 Leuven, Belgium. thomas.vanassche@med.kuleuven.be
authors.forename: Thomas
authors.initials: T
authors.lastname: Vanassche
authors.forename: Marijke
authors.initials: M
authors.lastname: Peetermans
authors.forename: Lucas N L
authors.initials: LN
authors.lastname: Van Aelst
authors.forename: Willy E
authors.initials: WE
authors.lastname: Peetermans
authors.forename: Jan
authors.initials: J
authors.lastname: Verhaegen
authors.forename: Dominique M
authors.initials: DM
authors.lastname: Missiakas
authors.forename: Olaf
authors.initials: O
authors.lastname: Schneewind
authors.forename: Marc F
authors.initials: MF
authors.lastname: Hoylaerts
authors.forename: Peter
authors.initials: P
authors.lastname: Verhamme
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D058491:Bacterial Load; D001562:Benzimidazoles / Q000494:pharmacology; D055499:Catheter-Related Infections / Q000209:etiology / Q000382:microbiology*; D062905:Central Venous Catheters / Q000382:microbiology; D003030:Coagulase / Q000378:metabolism / Q000502:physiology; D000069604:Dabigatran; D004195:Disease Models, Animal; D005337:Fibrin / Q000378:metabolism*; D007601:Jugular Veins; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013203:Staphylococcal Infections / Q000209:etiology / Q000382:microbiology*; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015091:beta-Alanine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D001562:Benzimidazoles; D003030:Coagulase; D015091:beta-Alanine; D005337:Fibrin; D013917:Thrombin; C022654:staphylothrombin; D000069604:Dabigatran
keywords: Staphylococcus aureus; catheter infection; dabigatran; staphylocoagulase; staphylothrombin; von Willebrand factor-binding protein