G15SecL05Tpc3: Difference between revisions
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==Significance in Lyme Disease and Bind Briefing== | ==Significance in Lyme Disease and Bind Briefing== | ||
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). | 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). | ||
==Osp-B/Antibody Binding Processes== | ==Osp-B/Antibody Binding Processes== | ||
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*2. Connolly S.E., Benach J.L. “The Versatile Roles of Antibodies in Borrelia Infections” Nature Reviews: Microbiology, Volume 3, May 2005, pp. 411-420 | *2. Connolly S.E., Benach J.L. “The Versatile Roles of Antibodies in Borrelia Infections” Nature Reviews: Microbiology, Volume 3, May 2005, pp. 411-420 | ||
*3. LaRocca T.J., Benach J.L. 2008 “The Important and Diverse Roles of Antibodies in the Host Response to Borrelia Infections” Specialization and Complementation of Humoral Immune Responses to in Infection. Current Topics in Microbiology and Immunology: pp. 319 | *3. LaRocca T.J., Benach J.L. 2008 “The Important and Diverse Roles of Antibodies in the Host Response to Borrelia Infections” Specialization and Complementation of Humoral Immune Responses to in Infection. Current Topics in Microbiology and Immunology: pp. 319 | ||
*4. Escudero R, Halluska ML, Backenson PB, Coleman JL, Benach JL. "Characterization of the Physiological Requirements for the Bactericidal Effects of a Monoclonal Antibody to OspB of Borrelia burgdorferi by Confocal Microscopy". Infect Immun. 1997; 65(5): pp. 1908-15 | *4. Escudero R, Halluska ML, Backenson PB, Coleman JL, Benach JL. "Characterization of the Physiological Requirements for the Bactericidal Effects of a Monoclonal Antibody to OspB of Borrelia burgdorferi by Confocal Microscopy". Infect Immun. 1997; 65(5): pp. 1908-15 | ||
*5. Sadziene A, Jonsson M, Bergström S, Bright RK, Kennedy RC, Barbour AG. "A Bactericidal Antibody to Borrelia burgdorferi is Directed Against a Variable Region of the OspB Protein". Infect Immun. 1994; 62(5): pp. 2037-45. | *5. Sadziene A, Jonsson M, Bergström S, Bright RK, Kennedy RC, Barbour AG. "A Bactericidal Antibody to Borrelia burgdorferi is Directed Against a Variable Region of the OspB Protein". Infect Immun. 1994; 62(5): pp. 2037-45. | ||
*6. Neelakanta G, Li X, Pal U, et al. "Outer Surface Protein B is Critical for Borrelia burgdorferi Adherence and Survival Within Ixodes Ticks". PLoS Pathog. 2007; 3(3): pp. 33 | |||
