title: BBA70 of Borrelia burgdorferi is a novel plasminogen-binding protein.
abstract: The Lyme disease spirochete Borrelia burgdorferi lacks endogenous, surface-exposed proteases. In order to efficiently disseminate throughout the host and penetrate tissue barriers, borreliae rely on recruitment of host proteases, such as plasmin(ogen). Here we report the identification of a novel plasminogen-binding protein, BBA70. Binding of plasminogen is dose-dependent and is affected by ionic strength. The BBA70-plasminogen interaction is mediated by lysine residues, primarily located in a putative C-terminal α-helix of BBA70. These lysine residues appear to interact with the lysine-binding sites in plasminogen kringle domain 4 because a deletion mutant of plasminogen lacking that domain was unable to bind to BBA70. Bound to BBA70, plasminogen activated by urokinase-type plasminogen activator was able to degrade both a synthetic chromogenic substrate and the natural substrate fibrinogen. Furthermore, BBA70-bound plasmin was able to degrade the central complement proteins C3b and C5 and inhibited the bacteriolytic effects of complement. Consistent with these functional activities, BBA70 is located on the borrelial outer surface. Additionally, serological evidence demonstrated that BBA70 is produced during mammalian infection. Taken together, recruitment and activation of plasminogen could play a beneficial role in dissemination of B. burgdorferi in the human host and may possibly aid the spirochete in escaping the defense mechanisms of innate immunity.
authors.affiliation: From the Institute of Medical Microbiology and Infection Control, University Hospital of Frankfurt, Paul-Ehrlich-Strasse 40, D-60596 Frankfurt, Germany.
authors.forename: Arno
authors.initials: A
authors.lastname: Koenigs
authors.affiliation: From the Institute of Medical Microbiology and Infection Control, University Hospital of Frankfurt, Paul-Ehrlich-Strasse 40, D-60596 Frankfurt, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Hammerschmidt
authors.affiliation: the Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, Lexington, Kentucky 40506.
authors.forename: Brandon L
authors.initials: BL
authors.lastname: Jutras
authors.affiliation: the Institute of Biochemistry, Goethe University of Frankfurt, Max-von-Laue-Strasse 9, D-60438 Frankfurt, Germany.
authors.forename: Denys
authors.initials: D
authors.lastname: Pogoryelov
authors.affiliation: the Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Beutenbergstrasse 11a, D-07745 Jena, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Barthel
authors.affiliation: the Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Beutenbergstrasse 11a, D-07745 Jena, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Skerka
authors.affiliation: Sekisui Virotech GmbH, Löwenplatz 5, D-65428 Rüsselsheim, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Kugelstadt
authors.affiliation: the Institute for Immunology, University of Heidelberg, Im Neuenheimer Feld 305, D-69120 Heidelberg, Germany, and.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Wallich
authors.affiliation: the Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, Lexington, Kentucky 40506.
authors.forename: Brian
authors.initials: B
authors.lastname: Stevenson
authors.affiliation: the Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Beutenbergstrasse 11a, D-07745 Jena, Germany,; Friedrich Schiller University, D-07743 Jena, Germany.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Zipfel
authors.affiliation: From the Institute of Medical Microbiology and Infection Control, University Hospital of Frankfurt, Paul-Ehrlich-Strasse 40, D-60596 Frankfurt, Germany,. Electronic address: kraiczy@em.uni-frankfurt.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Kraiczy
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D025065:Borrelia burgdorferi / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003179:Complement C3b / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003182:Complement C5 / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005341:Fibrinolysin / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D008193:Lyme Disease / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010958:Plasminogen / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014568:Urokinase-Type Plasminogen Activator / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D003182:Complement C5; D003179:Complement C3b; D010958:Plasminogen; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator
keywords: Borrelia; Complement; Host-Pathogen Interactions; Immune Evasion; Infectious Diseases; Innate Immunity; Plasminogen; Spirochetes