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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (SRC)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Texas Sw Medical Center Dallas
Schools of Medicine
United States
Zip Code
Caimano, Melissa J (2018) Generation of Mammalian Host-Adapted Borrelia burgdorferi by Cultivation in Peritoneal Dialysis Membrane Chamber Implantation in Rats. Methods Mol Biol 1690:35-45
Nally, Jarlath E; Grassmann, Andre A; Planchon, S├ębastien et al. (2017) Pathogenic Leptospires Modulate Protein Expression and Post-translational Modifications in Response to Mammalian Host Signals. Front Cell Infect Microbiol 7:362
Hawley, Kelly L; Cruz, Adriana R; Benjamin, Sarah J et al. (2017) IFN? Enhances CD64-Potentiated Phagocytosis of Treponema pallidum Opsonized with Human Syphilitic Serum by Human Macrophages. Front Immunol 8:1227
Grove, Arianna P; Liveris, Dionysios; Iyer, Radha et al. (2017) Two Distinct Mechanisms Govern RpoS-Mediated Repression of Tick-Phase Genes during Mammalian Host Adaptation by Borrelia burgdorferi, the Lyme Disease Spirochete. MBio 8:
Puthenveetil, Robbins; Kumar, Sanjiv; Caimano, Melissa J et al. (2017) The major outer sheath protein forms distinct conformers and multimeric complexes in the outer membrane and periplasm of Treponema denticola. Sci Rep 7:13260
Groshong, Ashley M; Dey, Abhishek; Bezsonova, Irina et al. (2017) Peptide Uptake Is Essential for Borrelia burgdorferi Viability and Involves Structural and Regulatory Complexity of its Oligopeptide Transporter. MBio 8:
Miller, Daniel P; Oliver Jr, Lee D; Tegels, Brittney K et al. (2016) The Treponema denticola FhbB Protein Is a Dominant Early Antigen That Elicits FhbB Variant-Specific Antibodies That Block Factor H Binding and Cleavage by Dentilisin. Infect Immun 84:2051-2058
Caimano, Melissa J; Drecktrah, Dan; Kung, Faith et al. (2016) Interaction of the Lyme disease spirochete with its tick vector. Cell Microbiol 18:919-27
Kenedy, Melisha R; Scott 2nd, Edgar J; Shrestha, Binu et al. (2016) Consensus computational network analysis for identifying candidate outer membrane proteins from Borrelia spirochetes. BMC Microbiol 16:141
Gulia-Nuss, Monika; Nuss, Andrew B; Meyer, Jason M et al. (2016) Genomic insights into the Ixodes scapularis tick vector of Lyme disease. Nat Commun 7:10507

Showing the most recent 10 out of 98 publications