title: Degradation of fibrinogen and collagen by staphopains, cysteine proteases released from Staphylococcus aureus.
abstract: Staphylococcus aureus is the most frequently isolated pathogen in gram-positive sepsis often complicated by a blood clotting disorder, and is the leading cause of infective endocarditis induced by bacterial destruction of endocardial tissues. The bacterium secretes cysteine proteases referred to as staphopain A (ScpA) and staphopain B (SspB). To investigate virulence activities of staphopains pertinent to clotting disorders and tissue destruction, we examined their effects on collagen, one of the major tissue components, and on plasma clotting. Both staphopains prolonged the partial thromboplastin time of plasma in a dose- and activity-dependent manner, with SspB being threefold more potent than ScpA. Staphopains also prolonged the thrombin time of both plasma and fibrinogen, indicating that these enzymes can cause impaired plasma clotting through fibrinogen degradation. Whereas SspB cleaved the fibrinogen Aα-chain at the C-terminal region very efficiently, ScpA degraded it rather slowly. This explains the superior ability of the former enzyme to impair fibrinogen clottability. Enzymically active staphopains, at concentrations as low as 10 nM, degraded collagen with comparable efficiency. These results show novel virulence activities of staphopains in degrading fibrinogen and collagen, and suggest an involvement of staphopains in the clotting impairment and tissue destruction caused by staphylococcal infection.
authors.affiliation: Department of Oral and Maxillo-Facial Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Takehisa
authors.initials: T
authors.lastname: Ohbayashi
authors.affiliation: Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Irie
authors.affiliation: Department of Molecular Pathology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.|Department of Urology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Murakami
authors.affiliation: Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Nowak
authors.affiliation: Department of Periodontics, Endodontics and Dental Hygiene, University of Louisville School of Dentistry, Louisville, KY 40202, USA.|Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Potempa
authors.affiliation: Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Nishimura
authors.affiliation: Department of Oral and Maxillo-Facial Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Shinohara
authors.affiliation: Department of Molecular Pathology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Imamura
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D001777:Blood Coagulation; D003094:Collagen / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D057056:Cysteine Proteases / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D013211:Staphylococcus aureus / Q000201:enzymology* / Q000472:pathogenicity; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D005340:Fibrinogen; D003094:Collagen; D057056:Cysteine Proteases; D003546:Cysteine Endopeptidases; C501295:staphopain A protein, Staphylococcus aureus; C479137:staphopain B protein, Staphylococcus aureus