Lyme disease involves multiple organs, induding the skin, heart, joints and nervous system. Following a tick bite, 6. burgdorieri are deposited in the skin of the mammalian host. Spirochetes reside in the dermis for about one week and then spread to many tissues throughout the body. The spirochetes colonize the joints, causing arthritis in botii mice and humans. The goal of this proposal is to characterize B. /wnawtoffjerf genes important in spirochete dissemination from the skin and colonization of the iolnts. The Identified gene products will then be targeted to interfere with specific phases ofthe spirochete life cvcle. These studies will use the murine model of tick-bome fi. bu/gdbfferr infedion, which partially mimics human disease, and specimens from patients with welldocumented Lyme disease. These data will lead to a greater understanding of how fi. burgdorferi gene expression contrit>utes to spirochete infectivity, and suggest new strategies for the prevention and treatment of Lyme disease.

Public Health Relevance

This project will lead to a greater understanding of the pathogenesis of, and Immunity against, Lyme disease. This infomnation will be useful for the development of new vaccines and therapeutics for this Important medical illness.

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 #
5R37AI049200-14
Application #
8636388
Study Section
Special Emphasis Panel (NSS)
Program Officer
Breen, Joseph J
Project Start
2001-05-01
Project End
2016-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
14
Fiscal Year
2014
Total Cost
$416,250
Indirect Cost
$166,250
Name
Yale University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Narasimhan, Sukanya; Rajeevan, Nallakkandi; Liu, Lei et al. (2014) Gut microbiota of the tick vector Ixodes scapularis modulate colonization of the Lyme disease spirochete. Cell Host Microbe 15:58-71
Krause, Peter J; Narasimhan, Sukanya; Wormser, Gary P et al. (2014) Borrelia miyamotoi sensu lato seroreactivity and seroprevalence in the northeastern United States. Emerg Infect Dis 20:1183-90
Narasimhan, Sukanya; Coumou, Jeroen; Schuijt, Tim J et al. (2014) A tick gut protein with fibronectin III domains aids Borrelia burgdorferi congregation to the gut during transmission. PLoS Pathog 10:e1004278
Schuijt, Tim J; Bakhtiari, Kamran; Daffre, Sirlei et al. (2013) Factor Xa activation of factor V is of paramount importance in initiating the coagulation system: lessons from a tick salivary protein. Circulation 128:254-66
Krause, Peter J; Narasimhan, Sukanya; Wormser, Gary P et al. (2013) Human Borrelia miyamotoi infection in the United States. N Engl J Med 368:291-3
Silver, Adam C; Dunne, Dana W; Zeiss, Caroline J et al. (2013) MyD88 deficiency markedly worsens tissue inflammation and bacterial clearance in mice infected with Treponema pallidum, the agent of syphilis. PLoS One 8:e71388
Yang, Xiuli; Hegde, Shylaja; Shroder, Deborah Y et al. (2013) The lipoprotein La7 contributes to Borrelia burgdorferi persistence in ticks and their transmission to naïve hosts. Microbes Infect 15:729-37
Ullmann, A J; Dolan, M C; Sackal, C A et al. (2013) Immunization with adenoviral-vectored tick salivary gland proteins (SALPs) in a murine model of Lyme borreliosis. Ticks Tick Borne Dis 4:160-3
Magnarelli, Louis A; Williams, Scott C; Norris, Steven J et al. (2013) Serum antibodies to Borrelia burgdorferi, Anaplasma phagocytophilum, and Babesia microti in recaptured white-footed mice. J Wildl Dis 49:294-302
Narasimhan, Sukanya; Perez, Oriana; Mootien, Sara et al. (2013) Characterization of Ixophilin, a thrombin inhibitor from the gut of Ixodes scapularis. PLoS One 8:e68012

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