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Infection and Immunity, May 2008, p. 2113-2122, Vol. 76, No. 5
0019-9567/08/$08.00+0     doi:10.1128/IAI.01266-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Identification of an Antiparallel Coiled-Coil/Loop Domain Required for Ligand Binding by the Borrelia hermsii FhbA Protein: Additional Evidence for the Role of FhbA in the Host-Pathogen Interaction{triangledown}

Kelley M. Hovis,1 John C. Freedman,1 Hongming Zhang,1 Jonathan L. Forbes,1 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 23298-06782

Received 14 September 2007/ Returned for modification 16 January 2008/ Accepted 13 February 2008

Borrelia hermsii, an etiological agent of tick-borne relapsing fever in North America, binds host-derived serum proteins including factor H (FH), plasminogen, and an unidentified 60-kDa protein via its FhbA protein. Two distinct phylogenetic types of FhbA have been delineated (FhbA1 and FhbA2). These orthologs share a conserved C-terminal domain that contains two alpha helices with a high predictive probability of coiled-coil formation that are separated by a 14-amino-acid loop domain. Through site-directed mutagenesis, we have identified residues within these domains that influence the binding of both mouse and human FH, plasminogen, and/or the 60-kDa protein. To further investigate the involvement of FhbA in the host-pathogen interaction, strains that are either FhbA+ (isolate YOR) or FhbA– (isolate REN) were tested for serum sensitivity. Significant differences were observed, with YOR and REN being serum resistant and serum sensitive (intermediate), respectively. To test the abilities of these strains to infect and persist in mice, mice were needle inoculated, and infectivity and persistence were then assessed. While both strains REN and YOR infected mice, only the FhbA+ YOR strain persisted beyond day 4. Survival of the YOR isolate in blood correlated with the upregulation of the fhbA gene, as demonstrated by real-time reverse transcriptase PCR. These data advance our understanding of the unique interactions of FhbA with individual serum proteins and provide support for the hypothesis that FhbA is an important contributor to the pathogenesis of the relapsing fever spirochete B. hermsii.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Medical College of Virginia at Virginia Commonwealth University, 1112 E. Clay St., Richmond, VA 23298-0678. Phone: (804) 828-3779. Fax: (804) 828-9946. E-mail: rmarconi{at}hsc.vcu.edu

{triangledown} Published ahead of print on 25 February 2008.

Editor: W. A. Petri, Jr.

Infection and Immunity, May 2008, p. 2113-2122, Vol. 76, No. 5
0019-9567/08/$08.00+0     doi:10.1128/IAI.01266-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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