title: Borrelia burgdorferi infection-associated surface proteins ErpP, ErpA, and ErpC bind human plasminogen.
abstract: Host-derived plasmin plays a critical role in mammalian infection by Borrelia burgdorferi. The Lyme disease spirochete expresses several plasminogen-binding proteins. Bound plasminogen is converted to the serine protease plasmin and thereby may facilitate the bacterium's dissemination throughout the host by degrading extracellular matrix. In this work, we demonstrate plasminogen binding by three highly similar borrelial outer surface proteins, ErpP, ErpA, and ErpC, all of which are expressed during mammalian infection. Extensive characterization of ErpP demonstrated that this protein bound in a dose-dependent manner to lysine binding site I of plasminogen. Removal of three lysine residues from the carboxy terminus of ErpP significantly reduced binding of plasminogen, and the presence of a lysine analog, epsilon-aminocaproic acid, inhibited the ErpP-plasminogen interaction, thus strongly pointing to a primary role for lysine residues in plasminogen binding. Ionic interactions are not required in ErpP binding of plasminogen, as addition of excess NaCl or the polyanion heparin did not have any significant effect on binding. Plasminogen bound to ErpP could be converted to the active enzyme, plasmin. The three plasminogen-binding Erp proteins can also bind the host complement regulator factor H. Plasminogen and factor H bound simultaneously and did not compete for binding to ErpP, indicating separate binding sites for both host ligands and the ability of the borrelial surface proteins to bind both host proteins.
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, MN 469, W. R. Willard Medical Education Building, Lexington, KY 40536-0298, USA. catherine.brissette@uky.edu
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Brissette
authors.forename: Katrin
authors.initials: K
authors.lastname: Haupt
authors.forename: Diana
authors.initials: D
authors.lastname: Barthel
authors.forename: Anne E
authors.initials: AE
authors.lastname: Cooley
authors.forename: Amy
authors.initials: A
authors.lastname: Bowman
authors.forename: Christina
authors.initials: C
authors.lastname: Skerka
authors.forename: Reinhard
authors.initials: R
authors.lastname: Wallich
authors.forename: Peter F
authors.initials: PF
authors.lastname: Zipfel
authors.forename: Peter
authors.initials: P
authors.lastname: Kraiczy
authors.forename: Brian
authors.initials: B
authors.lastname: Stevenson
mesh_terms: D000595:Amino Acid Sequence; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D025065:Borrelia burgdorferi / Q000502:physiology*; D017242:Complement Factor H / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010958:Plasminogen / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001425:Bacterial Outer Membrane Proteins; C534535:ErpA protein, Borrelia burgdorferi; C534536:ErpC protein, Borrelia burgdorferi; C534534:ErpP protein, Borrelia burgdorferi; D011956:Receptors, Cell Surface; D037521:Virulence Factors; D017242:Complement Factor H; D010958:Plasminogen