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Infection and Immunity, November 2007, p. 5272-5281, Vol. 75, No. 11
0019-9567/07/$08.00+0     doi:10.1128/IAI.00850-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Delineation of Species-Specific Binding Properties of the CspZ Protein (BBH06) of Lyme Disease Spirochetes: Evidence for New Contributions to the Pathogenesis of Borrelia spp.{triangledown}

Elizabeth A. Rogers1 and Richard T. Marconi1,2*

Department of Microbiology and Immunology, Medical College of Virginia at Virginia Commonwealth University,1 Center for the Study of Biological Complexity, Richmond, Virginia 23298-06782

Received 20 June 2007/ Returned for modification 26 July 2007/ Accepted 30 August 2007

Borrelia burgdorferi CspZ (TIGR open reading frame designation, BBH06) is part of a functionally related group of proteins that bind one or more members of the factor H (FH) protein family. In this report we assess the conservation, distribution, properties, and ligand binding abilities of CspZ from the three main Borrelia species associated with Lyme disease infections in humans. CspZ (also referred to as BbCRASP-2 in the literature) was found to be highly conserved at the intraspecies level but divergent at the interspecies level. All CspZ orthologs that originated from B. burgdorferi isolates bound FH from a diverse group of mammals. In contrast, CspZ derived from B. garinii and B. afzelii did not. Regardless of the Borrelia species of origin, all CspZ proteins tested bound to unknown ~60-kDa serum proteins produced by different mammals. To further define the molecular basis for the differential binding of CspZ orthologs to host proteins, DNA sequence, truncation, and site-directed mutagenesis analyses were performed. DNA sequence analyses revealed that B. garinii and B. afzelii CspZ orthologs possess a 64-amino-acid N-terminal domain that is absent from B. burgdorferi CspZ. However, binding analyses of recombinant proteins revealed that this domain does not in and of itself influence ligand binding properties. Truncation and mutagenesis analyses further revealed that the key determinants required for ligand binding are discontinuous and that the presentation of the ligand binding pocket is dependent on alpha helices with high coiled-coil formation probability. The data presented here provide insight into the molecular basis of CspZ-ligand interactions and suggest that CspZ orthologs from diverse Borrelia species can contribute to the host-pathogen interaction through their interaction with serum proteins.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Medical College of Virginia at Virginia Commonwealth University, McGuire Hall Room 101, 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 10 September 2007.

Editor: W. A. Petri, Jr.

Infection and Immunity, November 2007, p. 5272-5281, Vol. 75, No. 11
0019-9567/07/$08.00+0     doi:10.1128/IAI.00850-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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