Osp E Vaccine Potential

J Biol Chem. 2013 May 8. [Epub ahead of print]

Structural basis for complement evasion by Lyme disease pathogen Borrelia burgdorferi.

Bhattacharjee A, Oeemig JS, Kolodziejczyk R, Meri T, Kajander T, Lehtinen MJ, Iwaï H, Jokiranta TS, Goldman A.


University of Helsinki, Finland.


Borrelia burgdorferi spirochetes that cause Lyme borreliosis survive for a long time in human serum because they successfully evade the complement system, an important arm of innate immunity. The outer surface protein E (OspE) of B. burgdorferi is needed for this since it recruits complement regulator factor H (FH) onto the bacterial surface to evade complement-mediated cell lysis. To understand this process at the molecular level we used a structural approach. First, we solved the solution structure of OspE by NMR, revealing a fold that has not been seen before in proteins involved in complement regulation. Next, we solved the X-ray structure of the complex between OspE and the factor H (FH) C-terminal domains 19 and 20 (FH19-20) at 2.83 Å resolution. The structure shows that OspE binds FH19-20 in a way similar to, but not identical with, that used by endothelial cells to bind FH via glycosaminoglycans. The observed interaction of OspE with FH19-20 allows the full function of FH in down- regulation of complement activation on the bacteria. This reveals the molecular basis for how Borrelia burgdorferi evade innate immunity, and suggests how OspE could be used as a potential vaccine antigen.

Bb-CRASP, Borrelia, Complement, Immune evasion, Microbial pathogenesis, NMR, Outer surface protein E, Protein structure, X-ray crystallography, protein complex structure