Immune evasion of Borrelia miyamotoi : CbiA, a novel outer surface protein exhibiting complement binding and inactivating properties

  • Borrelia (B.) miyamotoi, an emerging tick-borne relapsing fever spirochete, resists complement-mediated killing. To decipher the molecular principles of immune evasion, we sought to identify determinants contributing to complement resistance. Employing bioinformatics, we identified a gene encoding for a putative Factor H-binding protein, termed CbiA (complement binding and inhibitory protein A). Functional analyses revealed that CbiA interacted with complement regulator Factor H (FH), C3, C3b, C4b, C5, and C9. Upon binding to CbiA, FH retained its cofactor activity for Factor I-mediated inactivation of C3b. The Factor H-binding site within CbiA was mapped to domain 20 whereby the C-terminus of CbiA was involved in FH binding. Additionally, CbiA directly inhibited the activation of the classical pathway and the assembly of the terminal complement complex. Of importance, CbiA displayed inhibitory activity when ectopically produced in serum-sensitive B. garinii G1, rendering this surrogate strain resistant to human serum. In addition, long-term in vitro cultivation lead to an incremental loss of the cbiA gene accompanied by an increase in serum susceptibility. In conclusion, our data revealed a dual strategy of B. miyamotoi to efficiently evade complement via CbiA, which possesses complement binding and inhibitory activities.

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Author:Florian Röttgerding, Alex Wagemakers, Joris Koetsveld, Volker Fingerle, Michael Kirschfink, Joppe W. HoviusORCiD, Peter F. ZipfelORCiDGND, Reinhard Wallich, Peter KraiczyGND
Pubmed Id:
Parent Title (English):Scientific reports
Publisher:Nature Publishing Group
Place of publication:London
Document Type:Article
Date of Publication (online):2017/04/06
Date of first Publication:2017/03/22
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2017/04/06
Issue:Nr. 1, Art. 303
Page Number:15
First Page:1
Last Page:15
This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit © The Author(s) 2017
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