IAI Accepts, published online ahead of print on 26 October 2009

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Infect. Immun. doi:10.1128/IAI.00691-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Functional characterization of Borrelia spielmanii outer surface proteins that interact with distinct members of the human factor H protein family and with plasminogen

Annekatrin Seling, Corinna Siegel, Volker Fingerle, Brandon L. Jutras, Catherine A. Brissette, Christine Skerka, Reinhard Wallich, Peter F. Zipfel, Brian Stevenson, and Peter Kraiczy^*

Institute of Medical Microbiology and Infection Control, University Hospital of Frankfurt, Paul-Ehrlich-Str. 40, D-60596 Frankfurt, Germany; Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, Veterinärstr. 2, D-85764 Oberschleißheim, Germany; Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, Lexington, Kentucky, USA; Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Beutenbergstr. 11a, D-07745 Jena, Germany; Institute for Immunology, University Hospital of Heidelberg, Im Neuenheimer Feld 305, 69120 Heidelberg, Germany; Friedrich Schiller University, Jena, Germany

^* To whom correspondence should be addressed. Email: Kraiczy{at}em.uni-frankfurt.de.

Acquisition of complement regulators factor H (CFH) and factor H-like protein 1 (CFHL1) from human serum enables Borrelia (B.) spielmanii, one of the etiological agents of Lyme disease, to evade complement-mediated killing by the human host. Up to three distinct complement regulator-acquiring surface proteins (CRASPs) may be expressed by serum-resistant B. spielmanii, each exhibiting an affinity for CFH and/or CFHL1. Here we describe the functional characterization of the 15-kDa CRASPs of B. spielmanii, members of the polymorphic Erp (OspE/F-related) protein family, that bind two distinct host complement regulators, CFH and factor H-related protein 1 (CFHR1), but not CFHL1. CFH bound to the B. spielmanii CRASPs maintained cofactor activity for factor I-mediated C3b inactivation. Three naturally-occurring alleles of this protein bound CFH and CFHR1, while a fourth natural allele could not. Comparative sequence analysis of these protein alleles identified a single amino acid, histidine-79, as playing a significant role in CFH/CFHR1-binding, with substitution by an arginine completely abrogating ligand binding. The mutation of His-79 to Arg did not inhibit binding of plasminogen, another known ligand of this group of borrelial outer-surface proteins.