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Originally published In Press as doi:10.1074/jbc.M007994200 on December 11, 2000

J. Biol. Chem., Vol. 276, Issue 11, 8427-8435, March 16, 2001
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The Complement Regulator Factor H Binds to the Surface Protein OspE of Borrelia burgdorferi*

Jens HellwageDagger §, Taru MeriDagger , Tero HeikkiläDagger , Antti AlitaloDagger , Jaana PaneliusDagger ||, Pekka LahdenneDagger , Ilkka J. T. SeppäläDagger ||, and Seppo MeriDagger ||**

From the Dagger  Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Haartmaninkatu 3, FIN-00014 Helsinki, Finland, the  Hospital for Children and Adolescents and || HUCH Laboratory Diagnostics, Helsinki University Central Hospital, Haartmaninkatu 4, FIN-00290 Helsinki, Finland, and the § Molecular Immunobiology Group, Hans Knoell Institute for Natural Products Research, Beutenbergstrasse 11a, D-07745 Jena, Germany

Spirochete bacteria of the Borrelia burgdorferi sensu lato complex cause Lyme borreliosis. The three pathogenic subspecies Borrelia garinii, Borrelia afzelii, and Borrelia burgdorferi sensu stricto differ in their disease profiles and susceptibility to complement lysis. We investigated whether complement resistance of Borreliae could be due to acquisition of the main soluble inhibitors of the alternative complement pathway, factor H and the factor H-like protein 1. When exposed to nonimmune EDTA-plasma, the serum-resistant B. afzelii and B. burgdorferi sensu stricto strains bound factor H/factor H-like protein 1 to their surfaces. Assays with radiolabeled proteins showed that factor H bound strongly to the B. burgdorferi sensu stricto strain. To identify factor H ligands on the borrelial surface, we analyzed a panel of outer surface proteins of B. burgdorferi sensu stricto with the surface plasmon resonance technique. The outer surface lipoprotein OspE was identified as a specific ligand for factor H. Using recombinant constructs of factor H, the binding site for OspE was localized to the C-terminal short consensus repeat domains 15-20. Specific binding of factor H to B. burgdorferi sensu stricto OspE may help the pathogen to evade complement attack and phagocytosis.

* This work was supported by the Life 2000 Program of the Academy of Finland, the Sigrid Jusélius Foundation, the Foundation for Pediatric Research, the Helsinki University Central Hospital Funds, the National Technology Agency of Finland, the University of Helsinki, and by a postdoctoral fellowship from the Hochschulsonderprogramm III of the Deutscher Akademischer Austauschdienst (to J. H.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

** To whom correspondence should be addressed: Dept. of Bacteriology and Immunology, Haartman Inst., University of Helsinki, Haartmaninkatu 3, FIN-00014 Helsinki, Finland. Tel.: 358-9-1912-6758; Fax: 358-9-1912-6382; E-mail: meri@helsinki.fi.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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J. Exp. Med., April 19, 2004; 199(8): 1077 - 1087.
[Abstract] [Full Text] [PDF]

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 Infect. Immun.Home page
J. J. Shin, A. V. Bryksin, H. P. Godfrey, and F. C. Cabello
Localization of BmpA on the Exposed Outer Membrane of Borrelia burgdorferi by Monospecific Anti-Recombinant BmpA Rabbit Antibodies
Infect. Immun., April 1, 2004; 72(4): 2280 - 2287.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
P. Kraiczy, J. Hellwage, C. Skerka, H. Becker, M. Kirschfink, M. M. Simon, V. Brade, P. F. Zipfel, and R. Wallich
Complement Resistance of Borrelia burgdorferi Correlates with the Expression of BbCRASP-1, a Novel Linear Plasmid-encoded Surface Protein That Interacts with Human Factor H and FHL-1 and Is Unrelated to Erp Proteins
J. Biol. Chem., January 23, 2004; 279(4): 2421 - 2429.
[Abstract] [Full Text] [PDF]

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 Infect. Immun.Home page
J. C. Miller, K. von Lackum, K. Babb, J. D. McAlister, and B. Stevenson
Temporal Analysis of Borrelia burgdorferi Erp Protein Expression throughout the Mammal-Tick Infectious Cycle
Infect. Immun., December 1, 2003; 71(12): 6943 - 6952.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
D. S. Pikas, E. L. Brown, S. Gurusiddappa, L. Y. Lee, Y. Xu, and M. Hook
Decorin-binding Sites in the Adhesin DbpA from Borrelia burgdorferi: A SYNTHETIC PEPTIDE APPROACH
J. Biol. Chem., August 15, 2003; 278(33): 30920 - 30926.
[Abstract] [Full Text] [PDF]

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 Infect. Immun.Home page
M. B. Lawrenz, R. M. Wooten, J. F. Zachary, S. M. Drouin, J. J. Weis, R. A. Wetsel, and S. J. Norris
Effect of Complement Component C3 Deficiency on Experimental Lyme Borreliosis in Mice
Infect. Immun., August 1, 2003; 71(8): 4432 - 4440.
[Abstract] [Full Text] [PDF]

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 J. Clin. Microbiol.Home page
J. V. McDowell, E. Tran, D. Hamilton, J. Wolfgang, K. Miller, and R. T. Marconi
Analysis of the Ability of Spirochete Species Associated with Relapsing Fever, Avian Borreliosis, and Epizootic Bovine Abortion To Bind Factor H and Cleave C3b
J. Clin. Microbiol., August 1, 2003; 41(8): 3905 - 3910.
[Abstract] [Full Text] [PDF]

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 Infect. Immun.Home page
R. Iyer, O. Kalu, J. Purser, S. Norris, B. Stevenson, and I. Schwartz
Linear and Circular Plasmid Content in Borrelia burgdorferi Clinical Isolates
Infect. Immun., July 1, 2003; 71(7): 3699 - 3706.
[Abstract] [Full Text] [PDF]

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 Infect. Immun.Home page
M. S. Metts, J. V. McDowell, M. Theisen, P. R. Hansen, and R. T. Marconi
Analysis of the OspE Determinants Involved in Binding of Factor H and OspE-Targeting Antibodies Elicited during Borreliaburgdorferi Infection in Mice
Infect. Immun., June 1, 2003; 71(6): 3587 - 3596.
[Abstract] [Full Text] [PDF]

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 Infect. Immun.Home page
J. V. McDowell, J. Wolfgang, E. Tran, M. S. Metts, D. Hamilton, and R. T. Marconi
Comprehensive Analysis of the Factor H Binding Capabilities of Borrelia Species Associated with Lyme Disease: Delineation of Two Distinct Classes of Factor H Binding Proteins
Infect. Immun., June 1, 2003; 71(6): 3597 - 3602.
[Abstract] [Full Text] [PDF]

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 J. Bacteriol.Home page
P. E. Stewart, G. Chaconas, and P. Rosa
Conservation of Plasmid Maintenance Functions between Linear and Circular Plasmids in Borrelia burgdorferi
J. Bacteriol., May 15, 2003; 185(10): 3202 - 3209.
[Abstract] [Full Text] [PDF]

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J. C. Miller and B. Stevenson
Immunological and genetic characterization of Borrelia burgdorferi BapA and EppA proteins
Microbiology, May 1, 2003; 149(5): 1113 - 1125.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
J. Hellwage, T. S. Jokiranta, M. A. Friese, T. U. Wolk, E. Kampen, P. F. Zipfel, and S. Meri
Complement C3b/C3d and Cell Surface Polyanions Are Recognized by Overlapping Binding Sites on the Most Carboxyl-Terminal Domain of Complement Factor H
J. Immunol., December 15, 2002; 169(12): 6935 - 6944.
[Abstract] [Full Text] [PDF]

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 Infect. Immun.Home page
T. G. Duthy, R. J. Ormsby, E. Giannakis, A. D. Ogunniyi, U. H. Stroeher, J. C. Paton, and D. L. Gordon
The Human Complement Regulator Factor H Binds Pneumococcal Surface Protein PspC via Short Consensus Repeats 13 to 15
Infect. Immun., October 1, 2002; 70(10): 5604 - 5611.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
A. Alitalo, T. Meri, H. Lankinen, I. Seppala, P. Lahdenne, P. S. Hefty, D. Akins, and S. Meri
Complement Inhibitor Factor H Binding to Lyme Disease Spirochetes Is Mediated by Inducible Expression of Multiple Plasmid-Encoded Outer Surface Protein E Paralogs
J. Immunol., October 1, 2002; 169(7): 3847 - 3853.
[Abstract] [Full Text] [PDF]

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 Infect. Immun.Home page
T. Meri, A. Hartmann, D. Lenk, R. Eck, R. Wurzner, J. Hellwage, S. Meri, and P. F. Zipfel
The Yeast Candida albicans Binds Complement Regulators Factor H and FHL-1
Infect. Immun., September 1, 2002; 70(9): 5185 - 5192.
[Abstract] [Full Text] [PDF]

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 Infect. Immun.Home page
B. Stevenson
Borrelia burgdorferi erp (ospE-Related) Gene Sequences Remain Stable during Mammalian Infection
Infect. Immun., September 1, 2002; 70(9): 5307 - 5311.
[Abstract] [Full Text] [PDF]

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 J. Bacteriol.Home page
N. El-Hage and B. Stevenson
Simultaneous Coexpression of Borrelia burgdorferi Erp Proteins Occurs through a Specific, erp Locus-Directed Regulatory Mechanism
J. Bacteriol., August 15, 2002; 184(16): 4536 - 4543.
[Abstract] [Full Text] [PDF]

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 Infect. Immun.Home page
B. Stevenson and K. Babb
LuxS-Mediated Quorum Sensing in Borrelia burgdorferi, the Lyme Disease Spirochete
Infect. Immun., August 1, 2002; 70(8): 4099 - 4105.
[Abstract] [Full Text] [PDF]

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 Infect. Immun.Home page
P. S. Hefty, S. E. Jolliff, M. J. Caimano, S. K. Wikel, and D. R. Akins
Changes in Temporal and Spatial Patterns of Outer Surface Lipoprotein Expression Generate Population Heterogeneity and Antigenic Diversity in the Lyme Disease Spirochete, Borrelia burgdorferi
Infect. Immun., July 1, 2002; 70(7): 3468 - 3478.
[Abstract] [Full Text] [PDF]

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 Infect. Immun.Home page
F. T. Liang, F. K. Nelson, and E. Fikrig
DNA Microarray Assessment of Putative Borrelia burgdorferi Lipoprotein Genes
Infect. Immun., June 1, 2002; 70(6): 3300 - 3303.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
T. Areschoug, M. Stalhammar-Carlemalm, I. Karlsson, and G. Lindahl
Streptococcal beta Protein Has Separate Binding Sites for Human Factor H and IgA-Fc
J. Biol. Chem., April 5, 2002; 277(15): 12642 - 12648.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
H. Jarva, R. Janulczyk, J. Hellwage, P. F. Zipfel, L. Bjorck, and S. Meri
Streptococcus pneumoniae Evades Complement Attack and Opsonophagocytosis by Expressing the pspC Locus-Encoded Hic Protein That Binds to Short Consensus Repeats 8-11 of Factor H
J. Immunol., February 15, 2002; 168(4): 1886 - 1894.
[Abstract] [Full Text] [PDF]

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 Infect. Immun.Home page
B. Stevenson, N. El-Hage, M. A. Hines, J. C. Miller, and K. Babb
Differential Binding of Host Complement Inhibitor Factor H by Borrelia burgdorferi Erp Surface Proteins: a Possible Mechanism Underlying the Expansive Host Range of Lyme Disease Spirochetes
Infect. Immun., February 1, 2002; 70(2): 491 - 497.
[Abstract] [Full Text] [PDF]

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 Infect. Immun.Home page
P. Kraiczy, C. Skerka, V. Brade, and P. F. Zipfel
Further Characterization of Complement Regulator-Acquiring Surface Proteins of Borrelia burgdorferi
Infect. Immun., December 1, 2001; 69(12): 7800 - 7809.
[Abstract] [Full Text] [PDF]

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 Infect. Immun.Home page
A. Alitalo, T. Meri, L. Ramo, T. S. Jokiranta, T. Heikkila, I. J. T. Seppala, J. Oksi, M. Viljanen, and S. Meri
Complement Evasion by Borrelia burgdorferi: Serum-Resistant Strains Promote C3b Inactivation
Infect. Immun., June 1, 2001; 69(6): 3685 - 3691.
[Abstract] [Full Text] [PDF]

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 Infect. Immun.Home page
K. Babb, N. El-Hage, J. C. Miller, J. A. Carroll, and B. Stevenson
Distinct Regulatory Pathways Control Expression of Borrelia burgdorferi Infection-Associated OspC and Erp Surface Proteins
Infect. Immun., June 1, 2001; 69(6): 4146 - 4153.
[Abstract] [Full Text] [PDF]


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