Jorge L. Benach

Research Interests (continued)

In collaboration with Dr Martha Furie and her group, we are also interested in the development of the chronic inflammatory changes that are the pathological hallmark of Lyme disease. The approaches here include characterizing the selective production of cytokines and chemokines, and the signaling pathways required for Borrelia and its outer surface molecules to induce the production of inflammatory mediators.

In a related project, we are studying the mechanism of action of bactericidal, complement-independent antibodies on Borrelia. Observations made in our laboratory point to a unique bactericidal mechanism that may represent a fundamental manner of host defense. A complement independent bactericidal monoclonal antibody (MAb) to an epitope in the outer surface lipoprotein B (OspB) of Borrelia burgdorferi has been discovered and fully characterized. This antibody, (CB2), and its Fab fragments had bactericidal activity against this organism in a medium devoid of complement. The epitope for CB2 was mapped to a linear hydrophilic region near the carboxy terminus of OspB, with an absolute requirement for a Lysine (Lys) residue in position 253. Absence of this Lys prevented binding as well as the bactericidal activity of the MAb. CB2 was used to select for mutants that were missing the plasmid encoding for OspB, or had mutations in the region of the critical Lys.

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