Borrelia burgdorferi is a tick-borne spirochete and the causative agent of Lyme disease. The focus of this renewal application is the biology of Lyme disease spirochetes within the tick vector. Studies have demonstrated that spirochetes delivered by ticks express different antigens compared to cultured spirochetes. Tick-borne spirochetes are able to better evade host immunity than cultured organisms. In this application we propose to use recently developed genetic tools to identify and study the function of Borrelia genes expressed in the vector.
In aim 1 we will focus on two Borrelia plasmids (lp25 and lp28-4) required for tick infection. We will identify specific genes on these plasmids required for infecting ticks. The focus of aim 2 will be two Borrelia outer membrane lipoproteins designated OspA and OspC. We will further refine existing models about the function of these proteins in ticks by using Borrelia mutants that inappropriately express these proteins. Studies of the interactions between Borrelia and ticks are significant because they have the potential to lead to vaccines that block transmission. We have demonstrated that specific antibody entering ticks is able to block the transmission of spirochetes by more than one mechanism.
In aim 3 we propose experiments to further dissect how Borrelia specific antibody entering ticks influence the phenotype of spirochetes and their transmission to the host. NARRATIVE Lyme disease is a tick-borne disease of people that is common in the USA and other parts of the world. The goal of this proposal is to study how Lyme disease bacteria are transmitted by ticks. The work is applicable to developing novel vaccines that prevent ticks from acquiring or transmitting Lyme disease bacteria.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR047948-10
Application #
8315911
Study Section
Bacterial Pathogenesis Study Section (BACP)
Program Officer
Mao, Su-Yau
Project Start
2002-04-15
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2014-08-31
Support Year
10
Fiscal Year
2012
Total Cost
$307,484
Indirect Cost
$98,396
Name
University of North Carolina Chapel Hill
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Srivastava, Siddharth Y; de Silva, Aravinda M (2009) Characterization of Borrelia burgdorferi aggregates. Vector Borne Zoonotic Dis 9:323-9
de Silva, Aravinda Manu; Tyson, Katharine Rose; Pal, Utpal (2009) Molecular characterization of the tick-Borrelia interface. Front Biosci 14:3051-63
Srivastava, Siddharth Y; de Silva, Aravinda M (2008) Reciprocal expression of ospA and ospC in single cells of Borrelia burgdorferi. J Bacteriol 190:3429-33
Nosbisch, Leanna K; de Silva, Aravinda M (2007) Lack of detectable variation at Borrelia burgdorferi vlsE locus in ticks. J Med Entomol 44:168-70
Strother, Keith O; Hodzic, Emir; Barthold, Stephen W et al. (2007) Infection of mice with lyme disease spirochetes constitutively producing outer surface proteins a and B. Infect Immun 75:2786-94
Rathinavelu, Sivaprakash; Broadwater, Anne; de Silva, Aravinda M (2003) Does host complement kill Borrelia burgdorferi within ticks? Infect Immun 71:822-9
Ohnishi, Jun; Schneider, Brad; Messer, William B et al. (2003) Genetic variation at the vlsE locus of Borrelia burgdorferi within ticks and mice over the course of a single transmission cycle. J Bacteriol 185:4432-41
Gipson, Clay L; Davis, Nancy L; Johnston, Robert E et al. (2003) Evaluation of Venezuelan Equine Encephalitis (VEE) replicon-based Outer surface protein A (OspA) vaccines in a tick challenge mouse model of Lyme disease. Vaccine 21:3875-84