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As previous studies focused almost exclusively on CspA of<jats:named-content content-type=\"genus-species\">B. burgdorferi<\/jats:named-content>, here we investigate the different binding capacities of CspA orthologs of<jats:named-content content-type=\"genus-species\">Borrelia burgdorferi<\/jats:named-content>,<jats:named-content content-type=\"genus-species\">B. afzelii<\/jats:named-content>, and<jats:named-content content-type=\"genus-species\">B. spielmanii<\/jats:named-content>for complement regulator factor H and plasminogen and their ability to inhibit complement activation by either binding these host-derived plasma proteins or independently by direct interaction with components involved in formation of the lethal, pore-like terminal complement complex. To further examine their function in serum resistance<jats:italic>in vivo<\/jats:italic>, a serum-sensitive<jats:named-content content-type=\"genus-species\">B. garinii<\/jats:named-content>strain was used to generate spirochetes, ectopically producing functional CspA orthologs. Irrespective of their species origin, all three CspA orthologs impart resistance to complement-mediated killing when produced in a serum-sensitive<jats:named-content content-type=\"genus-species\">B. garinii<\/jats:named-content>surrogate strain. To analyze the inhibitory effect on complement activation and to assess the potential to inactivate C3b by binding of factor H and plasminogen, recombinant CspA orthologs were also investigated. All three CspA orthologs simultaneously bound factor H and plasminogen but differed in regard to their capacity to inactivate C3b via bound plasmin(ogen) and inhibit formation of the terminal complement complex. CspA of<jats:named-content content-type=\"genus-species\">B. afzelii<\/jats:named-content>binds plasmin(ogen) and inhibits the terminal complement complex more efficiently than CspA of<jats:named-content content-type=\"genus-species\">B. burgdorferi<\/jats:named-content>and<jats:named-content content-type=\"genus-species\">B. spielmanii<\/jats:named-content>. Taken together, CspA orthologs of serum-resistant Lyme disease spirochetes act as multifunctional evasion molecules that inhibit complement on two central activation levels, C3b generation and assembly of the terminal complement complex.<\/jats:p>","DOI":"10.1128\/iai.01094-13","type":"journal-article","created":{"date-parts":[[2013,11,5]],"date-time":"2013-11-05T03:14:35Z","timestamp":1383621275000},"page":"380-392","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":57,"title":["Versatile Roles of CspA Orthologs in Complement Inactivation of Serum-Resistant Lyme Disease Spirochetes"],"prefix":"10.1128","volume":"82","author":[{"given":"Claudia","family":"Hammerschmidt","sequence":"first","affiliation":[{"name":"Institute of Medical Microbiology and Infection Control, University Hospital of Frankfurt, Frankfurt, 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