title: Tissue Plasminogen Activator Coating on Implant Surfaces Reduces Staphylococcus aureus Biofilm Formation.
abstract: Staphylococcus aureus biofilm infections of indwelling medical devices are a major medical challenge because of their high prevalence and antibiotic resistance. As fibrin plays an important role in S. aureus biofilm formation, we hypothesize that coating of the implant surface with fibrinolytic agents can be used as a new method of antibiofilm prophylaxis. The effect of tissue plasminogen activator (tPA) coating on S. aureus biofilm formation was tested with in vitro microplate biofilm assays and an in vivo mouse model of biofilm infection. tPA coating efficiently inhibited biofilm formation by various S. aureus strains. The effect was dependent on plasminogen activation by tPA, leading to subsequent local fibrin cleavage. A tPA coating on implant surfaces prevented both early adhesion and later biomass accumulation. Furthermore, tPA coating increased the susceptibility of biofilm infections to antibiotics. In vivo, significantly fewer bacteria were detected on the surfaces of implants coated with tPA than on control implants from mice treated with cloxacillin. Fibrinolytic coatings (e.g., with tPA) reduce S. aureus biofilm formation both in vitro and in vivo, suggesting a novel way to prevent bacterial biofilm infections of indwelling medical devices.
authors.affiliation: Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Jakub
authors.identifier: http://orcid.org/0000-0001-9472-2896
authors.initials: J
authors.lastname: Kwiecinski
authors.affiliation: Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Manli
authors.initials: M
authors.lastname: Na
authors.affiliation: Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Jarneborn
authors.affiliation: Department of Infectious Diseases, Skaraborg Hospital, Skövde, Sweden.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Jacobsson
authors.affiliation: Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
authors.forename: Marijke
authors.initials: M
authors.lastname: Peetermans
authors.affiliation: Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Verhamme
authors.affiliation: Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden tao.jin@rheuma.gu.se.
authors.forename: Tao
authors.identifier: http://orcid.org/0000-0001-9039-0628
authors.initials: T
authors.lastname: Jin
mesh_terms: D000818:Animals; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development*; D003023:Cloxacillin / Q000008:administration & dosage; D004195:Disease Models, Animal; D005337:Fibrin / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D013203:Staphylococcal Infections / Q000517:prevention & control*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development*; D013499:Surface Properties; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*
chemical_list: D005337:Fibrin; D010959:Tissue Plasminogen Activator; D003023:Cloxacillin