title: Staphylokinase Control of Staphylococcus aureus Biofilm Formation and Detachment Through Host Plasminogen Activation.
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.
authors.affiliation: Department of Rheumatology and Inflammation Research, Institute of Medicine.
authors.forename: Jakub
authors.initials: J
authors.lastname: Kwiecinski
authors.affiliation: Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, University of 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, Belgium.
authors.forename: Laurens
authors.initials: L
authors.lastname: Liesenborghs
authors.affiliation: Department of Rheumatology and Inflammation Research, Institute of Medicine.
authors.forename: Manli
authors.initials: M
authors.lastname: Na
authors.affiliation: Department of Rheumatology and Inflammation Research, Institute of Medicine.
authors.forename: Halla
authors.initials: H
authors.lastname: Björnsdottir
authors.affiliation: Department of Medical Biochemistry and Cell Biology.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Infectious Diseases, Skaraborg Hospital, Skövde, Sweden.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Jacobsson
authors.affiliation: Electron Microscopy Unit.
authors.forename: Bengt R
authors.initials: BR
authors.lastname: Johansson
authors.affiliation: Department of Microbiology, Moyne Institute of Preventive Medicine, School of Genetics and Microbiology, Trinity College, Dublin, Ireland.
authors.forename: Joan A
authors.initials: JA
authors.lastname: Geoghegan
authors.affiliation: Department of Microbiology, Moyne Institute of Preventive Medicine, School of Genetics and Microbiology, Trinity College, Dublin, Ireland.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Foster
authors.affiliation: Department of Rheumatology and Inflammation Research, Institute of Medicine.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Josefsson
authors.affiliation: Department of Rheumatology and Inflammation Research, Institute of Medicine Department of Oral Microbiology and Immunology, Sahlgrenska Academy at University of Gothenburg.
authors.forename: Johan
authors.initials: J
authors.lastname: Bylund
authors.affiliation: Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, University of Leuven, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Verhamme
authors.affiliation: Department of Rheumatology and Inflammation Research, Institute of Medicine.
authors.forename: Tao
authors.initials: T
authors.lastname: Jin
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects*; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D005260:Female; D005337:Fibrin / Q000378:metabolism; D008297:Male; D008666:Metalloendopeptidases / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D010958:Plasminogen / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D005337:Fibrin; D010958:Plasminogen; D008666:Metalloendopeptidases; C022653:auR protein, Staphylococcus aureus
keywords: Staphylococcus aureus; biofilm; fibrin; plasminogen; staphylokinase