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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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| Veröffentlicht in: | Scientific reports 7(2017) Artikel-Nummer 303, 15 Seiten |
|---|---|
| Personen und Körperschaften: | , , |
| Titel: | Immune evasion of Borrelia miyamotoi: CbiA, a novel outer surface protein exhibiting complement binding and inactivating properties/ Florian Röttgerding, Alex Wagemakers, Joris Koetsveld, Volker Fingerle, Michael Kirschfink, Joppe W. Hovius, Peter F. Zipfel, Reinhard Wallich and Peter Kraiczy |
| Format: | E-Book-Kapitel |
| Sprache: | Englisch |
| veröffentlicht: |
22 March 2017
|
| Gesamtaufnahme: |
: Scientific reports, 7(2017) Artikel-Nummer 303, 15 Seiten
, volume:7 |
| Quelle: | Verbunddaten SWB Lizenzfreie Online-Ressourcen |
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| 245 | 1 | 0 | |a Immune evasion of Borrelia miyamotoi |b CbiA, a novel outer surface protein exhibiting complement binding and inactivating properties |c Florian Röttgerding, Alex Wagemakers, Joris Koetsveld, Volker Fingerle, Michael Kirschfink, Joppe W. Hovius, Peter F. Zipfel, Reinhard Wallich and Peter Kraiczy |
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| 520 | |a 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 | Röttgerding, Florian, Kirschfink, Michael, Wallich, Reinhard |
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| contents | 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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| spelling | Röttgerding, Florian VerfasserIn (DE-588)1164718568 (DE-627)1029004390 (DE-576)510118763 aut, Immune evasion of Borrelia miyamotoi CbiA, a novel outer surface protein exhibiting complement binding and inactivating properties Florian Röttgerding, Alex Wagemakers, Joris Koetsveld, Volker Fingerle, Michael Kirschfink, Joppe W. Hovius, Peter F. Zipfel, Reinhard Wallich and Peter Kraiczy, 22 March 2017, Text txt rdacontent, Computermedien c rdamedia, Online-Ressource cr rdacarrier, Gesehen am 16.08.2018, 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., Kirschfink, Michael VerfasserIn (DE-588)120927152 (DE-627)080974457 (DE-576)292452411 aut, Wallich, Reinhard VerfasserIn (DE-588)1059566710 (DE-627)798640839 (DE-576)163467781 aut, Enthalten in Scientific reports [London] : Macmillan Publishers Limited, part of Springer Nature, 2011 7(2017) Artikel-Nummer 303, 15 Seiten Online-Ressource (DE-627)663366712 (DE-600)2615211-3 (DE-576)346641179 2045-2322 nnns, volume:7 year:2017, http://dx.doi.org/10.1038/s41598-017-00412-4 Verlag Resolving-System kostenfrei Volltext, https://www.nature.com/articles/s41598-017-00412-4 Verlag kostenfrei Volltext, http://dx.doi.org/10.1038/s41598-017-00412-4 LFER, LFER 2018-09-13T00:00:00Z |
| spellingShingle | Röttgerding, Florian, Kirschfink, Michael, Wallich, Reinhard, 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. |
| swb_id_str | 510118828 |
| title | Immune evasion of Borrelia miyamotoi: CbiA, a novel outer surface protein exhibiting complement binding and inactivating properties |
| title_auth | 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 Florian Röttgerding, Alex Wagemakers, Joris Koetsveld, Volker Fingerle, Michael Kirschfink, Joppe W. Hovius, Peter F. Zipfel, Reinhard Wallich and Peter Kraiczy |
| title_fullStr | Immune evasion of Borrelia miyamotoi CbiA, a novel outer surface protein exhibiting complement binding and inactivating properties Florian Röttgerding, Alex Wagemakers, Joris Koetsveld, Volker Fingerle, Michael Kirschfink, Joppe W. Hovius, Peter F. Zipfel, Reinhard Wallich and Peter Kraiczy |
| title_full_unstemmed | Immune evasion of Borrelia miyamotoi CbiA, a novel outer surface protein exhibiting complement binding and inactivating properties Florian Röttgerding, Alex Wagemakers, Joris Koetsveld, Volker Fingerle, Michael Kirschfink, Joppe W. Hovius, Peter F. Zipfel, Reinhard Wallich and Peter Kraiczy |
| title_in_hierarchy | Immune evasion of Borrelia miyamotoi: CbiA, a novel outer surface protein exhibiting complement binding and inactivating properties / Florian Röttgerding, Alex Wagemakers, Joris Koetsveld, Volker Fingerle, Michael Kirschfink, Joppe W. Hovius, Peter F. Zipfel, Reinhard Wallich and Peter Kraiczy, |
| title_short | Immune evasion of Borrelia miyamotoi |
| title_sort | immune evasion of borrelia miyamotoi cbia a novel outer surface protein exhibiting complement binding and inactivating properties |
| title_sub | CbiA, a novel outer surface protein exhibiting complement binding and inactivating properties |
| url | http://dx.doi.org/10.1038/s41598-017-00412-4, https://www.nature.com/articles/s41598-017-00412-4 |