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Infection and Immunity, April 2006, p. 2007-2014, Vol. 74, No. 4
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.4.2007-2014.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Molecular Analyses of the Interaction of Borrelia hermsii FhbA with the Complement Regulatory Proteins Factor H and Factor H-Like Protein 1

Kelley M. Hovis,1 Janice P. Jones,1 Tania Sadlon,3 Gauri Raval,1 David L. Gordon,3 and Richard T. Marconi1,2*

Department of Microbiology and Immunology,1 Center for the Study of Biological Complexity, Medical College of Virginia at Virginia Commonwealth University, Richmond, Virginia 23298-0678,2 Department of Microbiology and Infectious Diseases, Flinders Medical Centre, Bedford Park, South Australia, Australia3

Received 31 August 2005/ Returned for modification 21 November 2005/ Accepted 10 January 2006

Borrelia hermsii, the primary etiological agent of tick-borne relapsing fever in North America, binds the complement regulatory protein factor H (FH) as a means of evading opsonophagocytosis and the alternative complement pathway. The ability of FH-binding protein A (FhbA) to bind FH-like protein 1 (FHL-1) has not been assessed previously. In this study, using a whole-cell absorption assay, we demonstrated that B. hermsii absorbs both FH and FHL-1 from human serum. Consistent with this, affinity ligand binding immunoblot analyses revealed that FH constructs spanning short consensus repeats 1 to 7 and 16 to 20 bind to FhbA. To investigate the molecular basis of the interaction of FhbA with FH/FHL-1, recombinant FhbA truncated proteins were generated and tested for FH/FHL-1 binding. Binding required determinants located in both the N- and C-terminal domains of FhbA, suggesting that long-range intramolecular interactions are involved in the formation and presentation of the FH/FHL-1-binding pocket. To identify specific FhbA residues involved in binding, random mutagenesis was performed. These analyses identified a loop region of FhbA that may serve as a contact point for FH/FHL-1. The data presented here expand our understanding of the pathogenic mechanisms of the relapsing fever spirochetes and of the molecular nature of the interaction between FH/FHL-1 and FhbA.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Medical College of Virginia at Virginia Commonwealth University, Richmond, VA 23298-0678. Phone: (804) 828-3779. Fax: (804) 828-9946. E-mail: rmarconi{at}hsc.vcu.edu.

Editor: V. J. DiRita

Infection and Immunity, April 2006, p. 2007-2014, Vol. 74, No. 4
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.4.2007-2014.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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