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 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.
Institute of Medical Microbiology and Infection Control, University Hospital of Frankfurt, Paul Ehrlich Str. 40, D-60596 Frankfurt, Germany.
Annekatrin
A
Seling
Corinna
C
Siegel
Volker
V
Fingerle
Brandon L
BL
Jutras
Catherine A
CA
Brissette
Christine
C
Skerka
Reinhard
R
Wallich
Peter F
PF
Zipfel
Brian
B
Stevenson
Peter
P
Kraiczy
D000595:Amino Acid Sequence; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D001898:Borrelia / Q000378:metabolism*; D003167:Complement Activation; D017242:Complement Factor H / Q000235:genetics / Q000378:metabolism*; D003470:Culture Media; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008969:Molecular Sequence Data; D010958:Plasminogen / Q000378:metabolism*; D011485:Protein Binding; D044967:Serum / Q000737:chemistry
D001425:Bacterial Outer Membrane Proteins; D003470:Culture Media; D017242:Complement Factor H; D010958:Plasminogen