Identification and characterization of the factor H and FHL-1 binding complement regulator-acquiring surface protein 1 of the Lyme disease spirochete Borrelia spielmanii sp. nov

Borrelia spielmanii, one of the etiological agents of Lyme disease found in Europe, evades host complement-mediated killing by recruitment of the immune regulators factor H and FHL-1 from human serum. Serum-resistant and intermediate serum-resistant isolates express up to 3 distinct complement regul...

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Hauptverfasser: Herzberger, Pia (VerfasserIn) , Siegel, Corinna (VerfasserIn) , Skerka, Christine (VerfasserIn) , Fingerle, Volker (VerfasserIn) , Schulte-Spechtel, Ulrike (VerfasserIn) , Wilske, Bettina (VerfasserIn) , Brade, Volker (VerfasserIn) , Zipfel, Peter F. (VerfasserIn) , Wallich, Reinhard (VerfasserIn) , Kraiczy, Peter (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2009
In: International journal of medical microbiology
Year: 2009, Jahrgang: 299, Heft: 2, Pages: 141-154
ISSN:1618-0607
DOI:10.1016/j.ijmm.2008.06.005
Online-Zugang:Verlag, lizenzpflichtig, Volltext: http://dx.doi.org/10.1016/j.ijmm.2008.06.005
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/abs/pii/S1438422108000817
Volltext
Verfasserangaben:Pia Herzberger, Corinna Siegel, Christine Skerka, Volker Fingerle, Ulrike Schulte-Spechtel, Bettina Wilske, Volker Brade, Peter F. Zipfel, Reinhard Wallich, Peter Kraiczy

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520 |a Borrelia spielmanii, one of the etiological agents of Lyme disease found in Europe, evades host complement-mediated killing by recruitment of the immune regulators factor H and FHL-1 from human serum. Serum-resistant and intermediate serum-resistant isolates express up to 3 distinct complement regulator-acquiring surface proteins (CRASPs) that bind factor H and/or FHL-1. The present study describes identification and functional characterization of BsCRASP-1 as the dominant factor H and FHL-1 binding protein of B. spielmanii. BsCRASP-1 is a 27.7kDa outer surface lipoprotein, which after processing has a predicted mass of 24.9kDa. BsCRASP-1 is encoded by a single copy gene, cspA, that maps to a linear plasmid of approximately 55kb. Ligand affinity blot techniques revealed that both native and recombinant BsCRASP-1 from different isolates can strongly bind FHL-1, but only weakly factor H. Deletion mutants of recombinant BsCRASP-1 were generated and a high-affinity binding site for factor H and FHL-1 was mapped to its carboxy-terminal 10-amino-acid residue domain. Similarly, the dominant binding site of factor H and FHL-1 was localized to short consensus repeats (SCRs) 5-7. Factor H and FHL-1 maintained cofactor activity for factor I-mediated C3b inactivation when bound to full-length BsCRASP-1 but not to a deletion mutant lacking the carboxy-terminal 10-amino-acid residue domain. In conclusion, BsCRASP-1 binds the host immune regulators factor H and FHL-1, and is suggested to represent a key molecule of B. spielmanii for complement resistance. Thus, BsCRASP-1 most likely contributes to persistence of B. spielmanii and to pathogenesis of Lyme disease. 
650 4 |a Bacterial Outer Membrane Proteins 
650 4 |a Bacterial Proteins 
650 4 |a Binding Sites 
650 4 |a Borrelia 
650 4 |a Complement Factor H 
650 4 |a DNA, Bacterial 
650 4 |a Europe 
650 4 |a Gene Deletion 
650 4 |a Humans 
650 4 |a Intracellular Signaling Peptides and Proteins 
650 4 |a LIM Domain Proteins 
650 4 |a Lyme Disease 
650 4 |a Molecular Sequence Data 
650 4 |a Molecular Weight 
650 4 |a Muscle Proteins 
650 4 |a Plasmids 
650 4 |a Protein Binding 
650 4 |a Protein Interaction Domains and Motifs 
650 4 |a Protein Interaction Mapping 
650 4 |a Sequence Analysis, DNA 
650 4 |a Virulence Factors 
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