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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.
AuthorsJakub Kwiecinski, Manli Na, Anders Jarneborn, Gunnar Jacobsson, Marijke Peetermans, Peter Verhamme, Tao Jin
JournalApplied and environmental microbiology (Appl Environ Microbiol) Vol. 82 Issue 1 Pg. 394-401 (01 01 2016) ISSN: 1098-5336 [Electronic] United States
PMID26519394 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015, American Society for Microbiology. All Rights Reserved.
Chemical References
  • Fibrin
  • Tissue Plasminogen Activator
  • Cloxacillin
Topics
  • Animals
  • Biofilms (drug effects, growth & development)
  • Cloxacillin (administration & dosage)
  • Disease Models, Animal
  • Fibrin (metabolism)
  • Humans
  • In Vitro Techniques
  • Mice
  • Staphylococcal Infections (prevention & control)
  • Staphylococcus aureus (drug effects, growth & development)
  • Surface Properties
  • Tissue Plasminogen Activator (pharmacology)

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