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

Abstract

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.

• Authors: Annekatrin Seling, Corinna Siegel, Volker Fingerle, Brandon L Jutras, Catherine A Brissette, Christine Skerka, Reinhard Wallich, Peter F Zipfel, Brian Stevenson, Peter Kraiczy
• Journal: Infection and immunity (Infect Immun) Vol. 78 Issue 1 Pg. 39-48 (Jan 2010) ISSN: 1098-5522 [Electronic] United States
• PMID: 19858303 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Bacterial Outer Membrane Proteins
• Culture Media
• Complement Factor H
• Plasminogen

Topics

• Amino Acid Sequence
• Bacterial Outer Membrane Proteins (genetics, metabolism)
• Borrelia (metabolism)
• Complement Activation
• Complement Factor H (genetics, metabolism)
• Culture Media
• Gene Expression Regulation, Bacterial
• Humans
• Molecular Sequence Data
• Plasminogen (metabolism)
• Protein Binding
• Serum (chemistry)