The overall goal of this project is further characterization of the surface proteins of the Lyme disease agent, Borrelia burgdorferi sensu lato, and the interface between those proteins and the host's immune response, specifically antibodies.
The aims for this project are following: (I) To evaluate the variety and specificities of bactericidal antibodies to B. burgdorferi. This will be accomplished: (a) by producing and selecting other bactericidal antibodies from mice and humans using hybridoma technology and combinatorial immunoglobulin gene libraries in filamentous bacteriophage, and (b) by determining the epitopes for these antibodies. (II) To determine the mechanism of complement- independent bactericidal activity of antibodies to borrelias. This will be accomplished by (a) documenting the course and distribution of antibody binding to the cells, (b) assessing the environmental variables in bacterial cell death consequent to antibody binding, (c) determining if autolysis and other disturbances of macromolecular synthesis occurs after antibody binding, and (d) carrying out biophysical analysis of the Osp proteins and their interactions with antibody. (III) To further define the structure and membrane topology of the protein surface antigens of B. burgdorferi. This will be accomplished by (a) producing escape mutants with human antisera to recombinant OspA, (b) determining the mechanism of antibody resistance of mutants that retain the linear epitope for the selecting antibody, and (c) carrying out various studies of the physical associations between Osp proteins in the outer membrane.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI037248-04
Application #
2442630
Study Section
Special Emphasis Panel (SRC (75))
Project Start
1994-09-30
Project End
1999-06-30
Budget Start
1997-07-01
Budget End
1998-06-30
Support Year
4
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697
Barbour, Alan G; Bunikis, Jonas; Fish, Durland et al. (2015) Association between body size and reservoir competence of mammals bearing Borrelia burgdorferi at an endemic site in the northeastern United States. Parasit Vectors 8:299
Elfving, Karin; Olsen, Bjorn; Bergstrom, Sven et al. (2010) Dissemination of spotted fever rickettsia agents in Europe by migrating birds. PLoS One 5:e8572
Barbour, Alan G; Bunikis, Jonas; Travinsky, Bridgit et al. (2009) Niche partitioning of Borrelia burgdorferi and Borrelia miyamotoi in the same tick vector and mammalian reservoir species. Am J Trop Med Hyg 81:1120-31
Hanincova, Klara; Kurtenbach, Klaus; Diuk-Wasser, Maria et al. (2006) Epidemic spread of Lyme borreliosis, northeastern United States. Emerg Infect Dis 12:604-11
Ornstein, Katharina; Barbour, Alan G (2006) A reverse transcriptase-polymerase chain reaction assay of Borrelia burgdorferi 16S rRNA for highly sensitive quantification of pathogen load in a vector. Vector Borne Zoonotic Dis 6:103-12
Comstedt, Par; Bergstrom, Sven; Olsen, Bjorn et al. (2006) Migratory passerine birds as reservoirs of Lyme borreliosis in Europe. Emerg Infect Dis 12:1087-95
Becker, Michael; Bunikis, Jonas; Lade, Barbara D et al. (2005) Structural investigation of Borrelia burgdorferi OspB, a bactericidal Fab target. J Biol Chem 280:17363-70
Bunikis, Jonas; Barbour, Alan G (2005) Third Borrelia species in white-footed mice. Emerg Infect Dis 11:1150-1
Zhong, Jianmin; Barbour, Alan G (2004) Cross-species hybridization of a Borrelia burgdorferi DNA array reveals infection- and culture-associated genes of the unsequenced genome of the relapsing fever agent Borrelia hermsii. Mol Microbiol 51:729-48
Bunikis, Jonas; Garpmo, Ulf; Tsao, Jean et al. (2004) Sequence typing reveals extensive strain diversity of the Lyme borreliosis agents Borrelia burgdorferi in North America and Borrelia afzelii in Europe. Microbiology 150:1741-55

Showing the most recent 10 out of 33 publications