Human complement regulators C4b-binding protein and C1 esterase inhibitor interact with a novel outer surface protein of Borrelia recurrentis

The spirochete Borrelia recurrentis is the causal agent of louse-borne relapsing fever and is transmitted to humans by the infected body louse Pediculus humanus. We have recently demonstrated that the B. recurrentis surface receptor, HcpA, specifically binds factor H, the regulator of the alternativ...

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Hauptverfasser: Grosskinsky, Sonja (VerfasserIn) , Schott, Melanie (VerfasserIn) , Brenner, Christiane (VerfasserIn) , Cutler, Sally J. (VerfasserIn) , Simon, Markus M. (VerfasserIn) , Wallich, Reinhard (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: June 1, 2010
In: PLoS neglected tropical diseases
Year: 2010, Jahrgang: 4, Heft: 6, Pages: 1-12
ISSN:1935-2735
DOI:10.1371/journal.pntd.0000698
Online-Zugang:Verlag, lizenzpflichtig, Volltext: http://dx.doi.org/10.1371/journal.pntd.0000698
Volltext
Verfasserangaben:Sonja Grosskinsky, Melanie Schott, Christiane Brenner, Sally J. Cutler, Markus M. Simon, Reinhard Wallich

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520 |a The spirochete Borrelia recurrentis is the causal agent of louse-borne relapsing fever and is transmitted to humans by the infected body louse Pediculus humanus. We have recently demonstrated that the B. recurrentis surface receptor, HcpA, specifically binds factor H, the regulator of the alternative pathway of complement activation, thereby inhibiting complement mediated bacteriolysis. Here, we show that B. recurrentis spirochetes express another potential outer membrane lipoprotein, termed CihC, and acquire C4b-binding protein (C4bp) and human C1 esterase inhibitor (C1-Inh), the major inhibitors of the classical and lectin pathway of complement activation. A highly homologous receptor for C4bp was also found in the African tick-borne relapsing fever spirochete B. duttonii. Upon its binding to B. recurrentis or recombinant CihC, C4bp retains its functional potential, i.e. facilitating the factor I-mediated degradation of C4b. The additional finding that ectopic expression of CihC in serum sensitive B. burgdorferi significantly increased spirochetal resistance against human complement suggests this receptor to substantially contribute, together with other known strategies, to immune evasion of B. recurrentis. 
650 4 |a Amino Acid Sequence 
650 4 |a Bacterial Outer Membrane Proteins 
650 4 |a Binding Sites 
650 4 |a Borrelia 
650 4 |a Cell Death 
650 4 |a Cloning, Molecular 
650 4 |a Coenzymes 
650 4 |a Complement C1 Inhibitor Protein 
650 4 |a Complement C4b-Binding Protein 
650 4 |a Electrophoresis, Gel, Pulsed-Field 
650 4 |a Flow Cytometry 
650 4 |a Histocompatibility Antigens 
650 4 |a Humans 
650 4 |a Molecular Sequence Data 
650 4 |a Protein Binding 
650 4 |a Sequence Alignment 
650 4 |a Surface Properties 
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