SB2013 L08gr01: Difference between revisions

Lyme disease is a progressive multisystem disorder that produces a primary infection (erythema migrans), at an early stage, at the site of bite by Ixodes tick carrying spirochetes (Borrelia burgdorferi) and may spread to secondary sites (e.g. heat, nervous system, joints), if left untreated. Outer Surface Proteins (e.g. OspA, OspB and OspC) play a vital role in this infecting process. While inside the vector, presence of OspA is prominent while OspC is unexpressed on the spirochete outer membrane. When spirochetes invade the host body, OspA is suppressed and an upregulation of OspC occurs due to an induction in OspC synthesis (the surface proteins are co-regulated on the mRNA level). This upregulation of OspC occurs partially due to differential temperature change (the optimal temperature being 32-37 degrees C) in the host body. However, OspC expression decreases after 2 days (time needed for spirochete transmission) of feeding. This implies that OspC is a vital protein supporting the primary transmission of the antigen in the host body <ref name="kumara"> Kumaran D, Eswaramoorthy S, Luft B, Koide S, Dunn J, Lawson C, Swaminathan S. 2001. Crystal structure of outer surface protein C (OspC) from the Lyme disease spirochete,Borrelia burgdorferi. The EMBO Journal: United Kingdom. Vol.  20, No. 5. 8 p.Vol. 64, No.6.5. </ref>Furthermore, the tick-borne infection was shown to be prevented upon addressing active <ref name="gilmore>Gilmore R, Kappel K, Dolan M, Burkot T, Johnson B. Outer surface protein C (OspC), but not P39, is a protective immunogen against a tick-transmitted Borrelia burgdorferi challenge: evidence for a conformational protective epitope in OspC. 1996. Infection and Immunity.</ref> or passive <ref name="mbow">Mbow M, Gilmore R, Titus R. An OspC-specific monoclonal antibody passively protects mice from tick-transmitted infection by Borrelia burgdorferi B31. 1999. Infection and Immunity. Vol. 67. 2 p.</ref> immunization with various OspC formulations in experimental mammals. As a result, OspC is the protein of interest that is to be studied.  

The importance of this negative region is immense because it is likely to have a variety of functions. Initially it has been proposed that OspC may function in the cellular adhesion of Lyme disease because of its predisposition to bind to positively charged host ligands, such as extracellular glycoproteins like fibronectin. But more recent studies have suggested that the function of OspC may be entirely different. It is now understood that OspC plays a role in immobilizing plasminogen, suggesting that OspC is a biologically relevant plasminogen receptor on the surface of B. burgdorferi. Lyme disease, like many bacterial pathogens, cannot produce endogenous membrane-associated proteases and has to appropriate host proteases to increase the probability of successful host colonization <ref>Önder O, Humphrey PT, McOmber B, Korobova F, Francella N, Greenbaum DC, Brisson D.OspC Is Potent Plasminogen Receptor on Surface of Borrelia burgdorferi. 2011.</ref>.   

11.Zhong W, Gern L, Stehle T. Resolution of experimental and tick-borne Borrelia burgdorferi infection in mice by passive, but not active immunization using recombinant OspC. 1999. Eur. J. Immunol. Vol. 29, No. 3. 2 p.