Infection by Borrelia burgdorferi, the agent of Lyme disease, can cause clinical symptoms that commonly involve the skin, heart, joints and nervous system. Following the bite of Ixodes ticks, B. burgdorferi is initially deposited in the skin of a mammalian host, such as mice and humans. Spirochetes reside in the dermis for about one week - at which point a transient spirochetemia occurs - and B. burgdorferi then spread to various tissues, including the joints. The spirochetes colonize the joints, causing acute arthritis in both mice and humans. We hypothesize that B. burgdorferi preferentially expresses selected genes - at specific times and in precise locations - during its life cycle, and that the differentially regulated gene products contribute to spirochete pathogenesis. This project will focus on two of the most important locations that result in clinical symptoms - the skin and the joints - in the spirochete life cycle in vivo. The goal of this proposal is to identify and characterize B. burgdorferi genes that are important in (1) spirochete dissemination from the skin to distant tissues and (2) B. burgdorferi colonization of the joints -- and to then use this information to interrupt, or interfere with, specific aspects of the spirochete life cycle. The studies will use the well-characterized murine model of B. burgdorferi infection, which partially mimics human disease, and clinical specimens from patients with well-documented Lyme disease. These data will lead to a greater understanding of how tissue-specific B. burgdorferi gene expression contributes to spirochete survival, and suggest new strategies for the prevention and/or treatment of Lyme disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AI049200-10
Application #
7778326
Study Section
Host Interactions with Bacterial Pathogens Study Section (HIBP)
Program Officer
Breen, Joseph J
Project Start
2001-05-01
Project End
2011-03-31
Budget Start
2010-04-01
Budget End
2011-03-31
Support Year
10
Fiscal Year
2010
Total Cost
$357,579
Indirect Cost
Name
Yale University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
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