G15SecL05Tpc3: Difference between revisions

<scene name='G15SecL05Tpc3/Ospb/1'>Osp-B</scene> is a primary outer-surface lipoprotein molecule found in the Lyme disease spirochete ''Borrelia burgdorferi'', a molecule essential for the survival of the bacterium. Since its primary function is to serve both as a site of antibody recognition and as the microvillar attachment to the ''Ixodes scapularis'' midgut, it is constitutively expressed. Variation in the synthesis of Osp-B and other outer surface proteins is the means by which B. burgdorferi evades the host immune system and adapts to various host microenvironments, such as those in the common tick vector. B. burgdorferi selectively expresses specific Osps in distinct phases of its life cycle and in specific tissue locations: expression of B. burgdorferi OspB is immediately turned on when the spirochetes enter and reside within the tick vector. However, during transmission from the arthropod vector to a vertebrate host, B. burgdorferi down-regulates OspB expression and up-regulates the expression of proteins such as OspC, DbpA, and BBK32. This selective gene expression of Osp-B and other proteins in ticks suggests that these two proteins may function during early spirochete colonization and persistence within the tick vector (Cite).

Lyme disease is a bacterial infectious disease of the skin, joints, nervous system and heart dominantly caused by the spirochete ''Borrelia burgdorferi'',  transmitted to humans via the bite of the deer tick ''Ixodes scapularis'' (Becker et al, 2005). The importance of antibodies in controlling such spirochaetal infections was underscored by the discovery of two particular antibodies with distinctive bactericidal properties: the monoclonal antibodies CB2 and H6831 (Connoly et al, 2005). When directed against the C-terminus of the outer-surface protein Osp-B, these fragments are bactericidal even in the absence of complements or phagocytes (Sadziene et al, 1994). The formation of the OspB-CB2 and OspB-H6831 complexes were dependent upon a single lysine residue in Osp-B, Lys 253 ('''GREEN LINK THAT'''), for binding and thus leading to lysis of the outer membrane of the spirochete; the structural changes that result culminate into molecular instability and protease susceptibility that eventually lead to said lysis, though the exact physiological consequences of these changes are not yet fully sequenced nor understood (Connoly et al, 2005). These antibodies demonstrate enormous selective pressure; growth of ''Borrelia burgdorferi'' spirochetes in their presence generated escape mutants that lacked the critical Lys 253 amino acid on Osp-B for antibody binding, and were thus less infectious in experimental mouse models and ''in vitro'' experimental assays (Connoly et al, 2005).