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* Department of Bacteriology and Immunology, Haartman Institute and Helsinki University Central Hospital, and
Peptide and Protein Laboratory, Haartman Institute, University of Helsinki, Helsinki, Finland; and
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104
Borrelia burgdorferi spirochetes can circumvent the vertebrate host’s immune system for long periods of time. B. burgdorferi sensu stricto and B. afzelii, but not B. garinii, bind the complement inhibitor factor H to protect themselves against complement-mediated opsonophagocytosis and killing. We found that factor H binding and complement resistance are due to inducible expression of a wide repertoire of outer surface protein E (OspE) lipoproteins variably called OspE, p21, ErpA, and ErpP. Individual Borrelia strains carry multiple plasmid-encoded OspE paralogs. Together the OspE homologs were found to constitute an array of proteins that bind factor H via multiple C-terminal domains that are exposed outwards from the Borrelial surface. Charged residue substitutions in the key binding regions account for variations between OspE family members in the optimal binding pH, temperature, and ionic strength. This may help the spirochetes to adapt into various host environments. Our finding that multiple plasmid-encoded OspE proteins act as virulence factors of Borrelia can provide new tools for the prevention and treatment of borreliosis.
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A. Alitalo, T. Meri, T. Chen, H. Lankinen, Z.-Z. Cheng, T. S. Jokiranta, I. J. T. Seppala, P. Lahdenne, P. S. Hefty, D. R. Akins, et al. Lysine-Dependent Multipoint Binding of the Borrelia burgdorferi Virulence Factor Outer Surface Protein E to the C Terminus of Factor H J. Immunol., May 15, 2004; 172(10): 6195 - 6201. [Abstract] [Full Text] [PDF]
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K. Babb, J. D. McAlister, J. C. Miller, and B. Stevenson Molecular Characterization of Borrelia burgdorferi erp Promoter/Operator Elements J. Bacteriol., May 1, 2004; 186(9): 2745 - 2756. [Abstract] [Full Text] [PDF]
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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. 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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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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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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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. 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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