Complement regulator-acquiring surface proteins of Borrelia burgdorferi: a new protein family involved in complement resistance.
The innate immune system, particularly the host complement system, plays an important role in the elimination of invading pathogens. Borrelia burgdorferi, like other human pathogens, has developed strategies to prevent complement-mediated bacteriolysis. It is now well established that Borrelia differ in their complement resistance. In general terms, B. afzelii isolates are mainly resistant to complement-mediated bacteriolysis, whereas the majority of B. burgdorferi s.s. isolates display an intermediate complement-resistant phenotype. Most of the B. garinii isolates, in contrast, are efficiently killed by complement and, therefore, are classified as complement-sensitive. Complement resistance of B. afzelii and B. burgdorferi s.s. isolates correlates directly with the acquisition of the fluid-phase human complement regulators FHL-1/reconectin and factor H. To date, five distinct complement regulator-acquiring surface proteins (CRASPs) have been identified in B. afzelii and B. burgdorferi s.s. isolates. The individual CRASPs can be differentiated according to their size and their binding properties to FHL-1/reconectin and factor H. The domains that interact with CRASPs are localized at the C-terminal ends of these complement regulators. Thus, CRASPs represent a family of functional proteins involved in complement resistance of Borrelia. Furthermore, an alterable pattern of gene expression was observed for three CRASPs of B. afzelii: BaCRASP-1, BaCRASP-2, and BaCRASP-5 are up-regulated at 37 degrees C and down-regulated at 20 degrees C. The continued characterization of CRASPs at the molecular level is expected to identify new virulence factors and potential vaccine candidates.
Kraiczy
Peter
P
Institute of Medical Microbiology, Frankfurt University Hospital, Frankfurt, Germany. Kraiczy@em.uni-frankfurt.de
Skerka
Christine
C
Zipfel
Peter F
PF
Brade
Volker
V
D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D025065:Borrelia burgdorferi / Q000276:immunology* / Q000472:pathogenicity; D015748:Borrelia burgdorferi Group / Q000276:immunology* / Q000472:pathogenicity; D003167:Complement Activation / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D008193:Lyme Disease / Q000276:immunology* / Q000635:transmission; D008565:Membrane Proteins / Q000276:immunology*; D013045:Species Specificity
D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D008565:Membrane Proteins; C440651:complement regulator-acquiring surface proteins, Borrelia burgdorferi