Versatile roles of CspA orthologs in complement inactivation of serum-resistant Lyme disease spirochetes

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Claudia Hammerschmidt1, Arno Koenigs, Corinna Siegel

  • 1Institute of Medical Microbiology and Infection Control, University Hospital of Frankfurt, Frankfurt, Germany.

Infection and Immunity
|November 6, 2013
PubMed

Insights

Complement regulator factor H and plasminogen binding by Lyme disease spirochete CspA orthologs are key immune evasion strategies. These molecules inhibit complement activation at multiple levels, protecting the spirochetes from host immune responses.

Area of Science:

  • Microbiology
  • Immunology
  • Molecular Biology

Background:

  • CspA is a crucial immune evasion molecule for Lyme disease spirochetes, protecting them from complement-mediated killing.
  • Previous research on CspA has primarily focused on Borrelia burgdorferi.

Purpose of the Study:

  • To investigate the binding capacities of CspA orthologs from Borrelia burgdorferi, B. afzelii, and B. spielmanii for complement regulator factor H and plasminogen.
  • To assess the ability of these CspA orthologs to inhibit complement activation through plasma protein binding or direct interaction with the terminal complement complex.
  • To evaluate the in vivo function of CspA orthologs in conferring serum resistance.

Main Methods:

  • Ectopic production of functional CspA orthologs in a serum-sensitive B. garinii strain to assess in vivo serum resistance.
  • Investigation of recombinant CspA orthologs to analyze complement inhibition and C3b inactivation via factor H and plasminogen binding.
  • Comparative analysis of binding affinities and inhibitory capacities among different CspA orthologs.

Main Results:

  • All three CspA orthologs (from B. burgdorferi, B. afzelii, and B. spielmanii) conferred resistance to complement-mediated killing when expressed in a serum-sensitive B. garinii strain.
  • All CspA orthologs simultaneously bound factor H and plasminogen.
  • CspA of B. afzelii demonstrated more efficient plasminogen binding and inhibition of the terminal complement complex compared to orthologs from B. burgdorferi and B. spielmanii.

Conclusions:

  • CspA orthologs from serum-resistant Lyme disease spirochetes function as multifunctional immune evasion molecules.
  • These molecules inhibit complement activation at two critical levels: C3b generation and terminal complement complex assembly.
  • Differences in binding and inhibitory capacities among CspA orthologs highlight species-specific variations in immune evasion strategies.

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