Borrelia burgdorferi causes Lyme disease, the most common vector-borne disease in the United States. The spirochete has to change its gene expression during its life cycle in order to survive in the different environments that it encounters. p35 and p37 are unrelated genes with a coincident pattern of antibody response, peaking at around day 30 of infection and declining afterwards. Both genes are expressed early during infection, and may play a role in dissemination and colonization of the joints upon entering the mammalian host and cause arthritis. This project propose the use of genetic manipulation of clonal infectious B. burgdorferi in order to gain insight into the function of p35 and p37. Both genes will be inactivated by homologous recombination with an interrupted copy of the gene by insertion of a mutated gyrB gene (gyrBr), which confers resistance to coumermycin A1, the only selectable marker used successfully in non-infectious B. burgdorferi. The resultant mutants will be used to infect mice and study their ability to disseminate in the murine host, as well as their capacity to complete a natural cycle and cause disease. The ability to genetically manipulate infectious B. burgdorferi opens the possibility to study spirochetal gene function in natural conditions, and marks a forward step from gene description to the study of gene function in vivo.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Small Research Grants (R03)
Project #
7R03AR045740-03
Application #
6171183
Study Section
Special Emphasis Panel (ZAR1-JRL-A (O1))
Program Officer
Gretz, Elizabeth
Project Start
1998-09-30
Project End
2002-02-28
Budget Start
2000-09-01
Budget End
2002-02-28
Support Year
3
Fiscal Year
2000
Total Cost
$65,000
Indirect Cost
Name
University of North Carolina Charlotte
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
066300096
City
Charlotte
State
NC
Country
United States
Zip Code
28223
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Rasley, Amy; Anguita, Juan; Marriott, Ian (2002) Borrelia burgdorferi induces inflammatory mediator production by murine microglia. J Neuroimmunol 130:22-31
Anguita, Juan; Samanta, Swapna; Ananthanarayanan, Shobana K et al. (2002) Cyclooxygenase 2 activity modulates the severity of murine Lyme arthritis. FEMS Immunol Med Microbiol 34:187-91
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