Contribution of the Infection-Associated Complement Regulator-Acquiring Surface Protein 4 (ErpC) to Complement Resistance ofBorrelia burgdorferi

Claudia Hammerschmidt,Brian Stevenson,Reinhard Wallich,Christine Skerka,Teresia Hallström,Peter Kraiczy,Peter F Zipfel

doi:10.1155/2012/349657

Abstract

Borrelia burgdorferi evades complement-mediated killing by interacting with complement regulators through distinct complement regulator-acquiring surface proteins (CRASPs). Here, we extend our analyses to the contribution of CRASP-4 in mediating complement resistance of B. burgdorferi and its interaction with human complement regulators. CRASP-4 (also known as ErpC) was immobilized onto magnetic beads and used to capture proteins from human serum. Following Western blotting, factor H (CFH), CFH-related protein 1 (CFHR1), CFHR2, and CFHR5 were identified as ligands of CRASP-4. To analyze the impact of native CRASP-4 on mediating survival of serum-sensitive cells in human serum, a B. garinii strain was generated that ectopically expresses CRASP-4. CRASP-4-producing bacteria bound CFHR1, CFHR2, and CFHR5 but not CFH. In addition, transformed spirochetes deposited significant amounts of lethal complement components on their surface and were susceptible to human serum, thus indicating that CRASP-4 plays a subordinate role in complement resistance of B. burgdorferi.

Highlights

Lyme borreliosis, caused by spirochetes of the Borrelia burgdorferi sensu lato complex, is the most prevalent vectorborne anthropozoonosis in Eurasia and the United States [1]
Elucidation of the underlying molecular mechanism(s) of complement resistance among Lyme disease spirochetes revealed that binding of the host complement regulators factor H (CFH) and factor H-like protein 1 (FHL1) to the bacterial surface directly correlates with serum resistance [3, 6,7,8,9,10]
We extended our previous investigations on the CFH- and CFH-related protein 1 (CFHR1) binding capacity of complement regulator-acquiring surface proteins (CRASPs)-4/ErpC protein to additional proteins derived from human serum and their contributions to convey complement resistance

Summary

Introduction

Lyme borreliosis, caused by spirochetes of the Borrelia burgdorferi sensu lato complex, is the most prevalent vectorborne anthropozoonosis in Eurasia and the United States [1]. It has been shown that certain genospecies resist complement-mediated killing of human serum, in particular B. burgdorferi sensu stricto (hereafter referred to as B. burgdorferi), B. afzelii, B. spielmanii, and B. bavariensis (formerly known as B. garinii OspA serotype 4 strains) [2,3,4,5]. Elucidation of the underlying molecular mechanism(s) of complement resistance among Lyme disease spirochetes revealed that binding of the host complement regulators factor H (CFH) and factor H-like protein 1 (FHL1) to the bacterial surface directly correlates with serum resistance [3, 6,7,8,9,10]. B. garinii, B. valaisiana, and B. lusitaniae are highly susceptible to complement-mediated killing and either do not bind, or bind inadequate levels of complement regulators [2, 4, 10,11,12].

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Conclusion