The complement binding and inhibitory protein CbiA of borrelia miyamotoi degrades extracellular matrix components by interacting with plasmin(ogen)

  • The emerging relapsing fever spirochete Borrelia (B.) miyamotoi is transmitted by ixodid ticks and causes the so-called hard tick-borne relapsing fever or B. miyamotoi disease (BMD). More recently, we identified a surface-exposed molecule, CbiA exhibiting complement binding and inhibitory capacity and rendering spirochetes resistant to complement-mediated lysis. To gain deeper insight into the molecular principles of B. miyamotoi-host interaction, we examined CbiA as a plasmin(ogen) receptor that enables B. miyamotoi to interact with the serine protease plasmin(ogen). Recombinant CbiA was able to bind plasminogen in a dose-dependent fashion. Moreover, lysine residues appear to play a crucial role in the protein-protein interaction as binding of plasminogen was inhibited by the lysine analog tranexamic acid as well as increasing ionic strength. Of relevance, plasminogen bound to CbiA can be converted by urokinase-type plasminogen activator (uPa) to active plasmin which cleaved both, the chromogenic substrate S-2251 and its physiologic substrate fibrinogen. Concerning the involvement of specific amino acids in the interaction with plasminogen, lysine residues located at the C-terminus are frequently involved in the binding as reported for various other plasminogen-interacting proteins of Lyme disease spirochetes. Lysine residues located within the C-terminal domain were substituted with alanine to generate single, double, triple, and quadruple point mutants. However, binding of plasminogen to the mutated CbiA proteins was not affected, suggesting that lysine residues distant from the C-terminus might be involved in the interaction.

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Author:Ngoc-Thach Nguyen, Florian Röttgerding, Gayatri Devraj, Yi-Pin LinORCiD, Arno Koenigs, Peter KraiczyGND
Pubmed Id:
Parent Title (English):Frontiers in Cellular and Infection Microbiology
Publisher:Frontiers Media
Place of publication:Lausanne
Contributor(s):Linden Hu
Document Type:Article
Year of Completion:2018
Date of first Publication:2018/02/02
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/05/17
Tag:Borrelia miyamotoi; borrelia; fibrinolysis; lyme disease; plasminogen; spirochetes
Issue:Art. 23
Page Number:12
First Page:1
Last Page:12
Copyright: © 2018 Nguyen, Röttgerding, Devraj, Lin, Koenigs and Kraiczy. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0