Staphylokinase control of Staphylococcus aureus biofilm formation and detachment through host plasminogen activation

Jakub Kwiecinski, Marijke Peetermans, Laurens Liesenborghs, Manli Na, Halla Björnsdottir, Xuefeng Zhu, Gunnar Jacobsson, Bengt R Johansson, Joan A Geoghegan, Timothy J Foster, Elisabet Josefsson, Johan Bylund, Peter Verhamme, Tao Jin

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Abstract

Staphylococcus aureus biofilms, a leading cause of persistent infections, are highly resistant to immune defenses and antimicrobial therapies. In the present study, we investigated the contribution of fibrin and staphylokinase (Sak) to biofilm formation. In both clinical S. aureus isolates and laboratory strains, high Sak-producing strains formed less biofilm than strains that lacked Sak, suggesting that Sak prevents biofilm formation. In addition, Sak induced detachment of mature biofilms. This effect depended on plasminogen activation by Sak. Host-derived fibrin, the main substrate cleaved by Sak-activated plasminogen, was a major component of biofilm matrix, and dissolution of this fibrin scaffold greatly increased susceptibility of biofilms to antibiotics and neutrophil phagocytosis. Sak also attenuated biofilm-associated catheter infections in mouse models. In conclusion, our results reveal a novel role for Sak-induced plasminogen activation that prevents S. aureus biofilm formation and induces detachment of existing biofilms through proteolytic cleavage of biofilm matrix components.

Original languageEnglish
JournalJournal of Infectious Diseases
Volume213
Issue number1
Pages (from-to)139-148
Number of pages10
ISSN0022-1899
DOIs
Publication statusPublished - 2016

Keywords

  • Animals
  • Anti-Bacterial Agents/pharmacology
  • Biofilms/drug effects
  • Drug Resistance, Bacterial/drug effects
  • Female
  • Fibrin/metabolism
  • Male
  • Metalloendopeptidases/metabolism
  • Mice
  • Mice, Inbred C57BL
  • Plasminogen/metabolism
  • Staphylococcus aureus/drug effects

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