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

Acquisition of complement regulator factor H (CFH) and factor H-like protein 1 (CFHL1) from human serum enables Borrelia 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 prot...

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Hauptverfasser: Seling, Annekatrin (VerfasserIn) , Siegel, Corinna (VerfasserIn) , Fingerle, Volker (VerfasserIn) , Jutras, Brandon L. (VerfasserIn) , Brissette, Catherine A. (VerfasserIn) , Skerka, Christine (VerfasserIn) , Wallich, Reinhard (VerfasserIn) , Zipfel, Peter F. (VerfasserIn) , Stevenson, Brian (VerfasserIn) , Kraiczy, Peter (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2010
In: Infection and immunity
Year: 2009, Jahrgang: 78, Heft: 1, Pages: 39-48
ISSN:1098-5522
DOI:10.1128/IAI.00691-09
Online-Zugang:Verlag, Volltext: https://dx.doi.org/10.1128/IAI.00691-09
Verlag, Volltext: https://iai.asm.org/content/78/1/39
Volltext
Verfasserangaben:Annekatrin Seling, Corinna Siegel, Volker Fingerle, Brandon L. Jutras, Catherine A. Brissette, Christine Skerka, Reinhard Wallich, Peter F. Zipfel, Brian Stevenson, and Peter Kraiczy
Beschreibung
Zusammenfassung:Acquisition of complement regulator factor H (CFH) and factor H-like protein 1 (CFHL1) from human serum enables Borrelia 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.
Beschreibung:Published ahead of print on 26 October 2009
Gesehen am 19.05.2021
Beschreibung:Online Resource
ISSN:1098-5522
DOI:10.1128/IAI.00691-09

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