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Infection and Immunity, January 2009, p. 300-306, Vol. 77, No. 1
0019-9567/09/$08.00+0     doi:10.1128/IAI.01133-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Borrelia burgdorferi Infection-Associated Surface Proteins ErpP, ErpA, and ErpC Bind Human Plasminogen{triangledown}

Catherine A. Brissette,1,{dagger}* Katrin Haupt,2,{dagger} Diana Barthel,2 Anne E. Cooley,1,{ddagger} Amy Bowman,1 Christina Skerka,2 Reinhard Wallich,3 Peter F. Zipfel,2,4 Peter Kraiczy,5 and Brian Stevenson1

Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, Kentucky,1 Leibniz Institute for Natural Product Research, Jena, Germany,2 University of Heidelberg, Heidelberg, Germany,3 Friedrich Schiller University, Jena, Germany,4 Institute of Medical Microbiology and Infection Control, University Hospital of Frankfurt, Frankfurt am Main, Germany5

Received 10 September 2008/ Returned for modification 24 October 2008/ Accepted 30 October 2008

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, {varepsilon}-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.

* Corresponding author. Mailing address: 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. Phone: (859) 257-9305. Fax: (859) 257-8994. E-mail: catherine.brissette{at}uky.edu

{triangledown} Published ahead of print on 10 November 2008.

Editor: R. P. Morrison

{dagger} C.A.B. and K.H. contributed equally to this work.

{ddagger} Present address: Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.

Infection and Immunity, January 2009, p. 300-306, Vol. 77, No. 1
0019-9567/09/$08.00+0     doi:10.1128/IAI.01133-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



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