It is generally thought that the major protein immunogens of Borrelia burgdorferi, particularly the well characterized OspA and OspB molecules, are surface-exposed outer membrane proteins. A major problem with this concept is that it fails to explain how virulent. B. burgdorferi withstands the intensive antibody response elicited by these proteins in patients with chronic Lyme Disease. This consideration, along with evidence in Preliminary Studies, prompts a reevaluation of current concepts of B. burgdorferi antigen structure. Our key discoveries are that 1) a number of the major immunogens of B. burgdorferi, including Osps A and B, are lipoproteins and 2) the organism appears to contain two distinct classes of integral membrane proteins: (a) abundant lipoprotein immunogens and (b) classical transmembrane proteins of relatively low abundance and immunogenicity. This latter group may include molecules that are important in Lyme Disease pathogenesis. The putative low abundance outer membrane proteins will be characterized by 2D-electrophoretic analysis of total membrane proteins of B. burgdorferi and by isolation of outer and cytoplasmic membrane fractions. The precise cellular locations and the membrane topologies of the Osp immunogens will be investigated by a combination of immunoelectron microscopy and freeze fracture/freeze-etch electron microscopy. Using biochemical and molecular approaches, the lipoprotein structures of the major immunogens will be analyzed in order to define constituent lipopeptides with immunological activity. The proposed studies will markedly improve our limited understanding of the relationship between B. burgdorferi ultrastructure and its ability to evade host immune defense.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI029735-03
Application #
3144651
Study Section
Special Emphasis Panel (SRC)
Project Start
1990-04-01
Project End
1995-03-31
Budget Start
1992-04-01
Budget End
1993-03-31
Support Year
3
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Type
Schools of Medicine
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75390
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