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

Abstract 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 e...

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Autores principales:	Florian Röttgerding, Alex Wagemakers, Joris Koetsveld, Volker Fingerle, Michael Kirschfink, Joppe W. Hovius, Peter F. Zipfel, Reinhard Wallich, Peter Kraiczy
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d332e145360d4ee0b985697b6a40fcbf
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spelling	oai:doaj.org-article:d332e145360d4ee0b985697b6a40fcbf2021-12-02T12:32:41ZImmune evasion of Borrelia miyamotoi: CbiA, a novel outer surface protein exhibiting complement binding and inactivating properties10.1038/s41598-017-00412-42045-2322https://doaj.org/article/d332e145360d4ee0b985697b6a40fcbf2017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00412-4https://doaj.org/toc/2045-2322Abstract 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.Florian RöttgerdingAlex WagemakersJoris KoetsveldVolker FingerleMichael KirschfinkJoppe W. HoviusPeter F. ZipfelReinhard WallichPeter KraiczyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Florian Röttgerding Alex Wagemakers Joris Koetsveld Volker Fingerle Michael Kirschfink Joppe W. Hovius Peter F. Zipfel Reinhard Wallich Peter Kraiczy Immune evasion of Borrelia miyamotoi: CbiA, a novel outer surface protein exhibiting complement binding and inactivating properties
description	Abstract 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.
format	article
author	Florian Röttgerding Alex Wagemakers Joris Koetsveld Volker Fingerle Michael Kirschfink Joppe W. Hovius Peter F. Zipfel Reinhard Wallich Peter Kraiczy
author_facet	Florian Röttgerding Alex Wagemakers Joris Koetsveld Volker Fingerle Michael Kirschfink Joppe W. Hovius Peter F. Zipfel Reinhard Wallich Peter Kraiczy
author_sort	Florian Röttgerding
title	Immune evasion of Borrelia miyamotoi: CbiA, a novel outer surface protein exhibiting complement binding and inactivating properties
title_short	Immune evasion of Borrelia miyamotoi: CbiA, a novel outer surface protein exhibiting complement binding and inactivating properties
title_full	Immune evasion of Borrelia miyamotoi: CbiA, a novel outer surface protein exhibiting complement binding and inactivating properties
title_fullStr	Immune evasion of Borrelia miyamotoi: CbiA, a novel outer surface protein exhibiting complement binding and inactivating properties
title_full_unstemmed	Immune evasion of Borrelia miyamotoi: CbiA, a novel outer surface protein exhibiting complement binding and inactivating properties
title_sort	immune evasion of borrelia miyamotoi: cbia, a novel outer surface protein exhibiting complement binding and inactivating properties
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/d332e145360d4ee0b985697b6a40fcbf
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Immune evasion of Borrelia miyamotoi: CbiA, a novel outer surface protein exhibiting complement binding and inactivating properties

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