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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| Main Authors: | , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2009
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| In: |
International journal of medical microbiology
Year: 2009, Volume: 299, Issue: 2, Pages: 141-154 |
| ISSN: | 1618-0607 |
| DOI: | 10.1016/j.ijmm.2008.06.005 |
| Online Access: | 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 
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| Author Notes: | Pia Herzberger, Corinna Siegel, Christine Skerka, Volker Fingerle, Ulrike Schulte-Spechtel, Bettina Wilske, Volker Brade, Peter F. Zipfel, Reinhard Wallich, Peter Kraiczy |
| Summary: | 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. |
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| Item Description: | Gesehen am 04.06.2021 |
| Physical Description: | Online Resource |
| ISSN: | 1618-0607 |
| DOI: | 10.1016/j.ijmm.2008.06.005 |