Jenifer Coburn, PhD
Professor
Medicine (Division of Infectious Disease), and Center for Infectious Disease Research
Medical College of Wisconsin
Research Focus: Spirochete Pathogenesis and Host Cell Responses
PhD: Tufts University (1991) Molecular Microbiology
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My laboratory studies the interactions with mammalian cells of Borrelia burgdorferi, the agent of Lyme disease, and Leptospira interrogans, an agent of leptospirosis. Both are spirochetes that can establish persistent infection in immunocompetent reservoir animals, and are significant causes of morbidity and mortality in humans. While leptospirosis is uncommon in the continental US, it is a significant illness in agricultural and urban slum areas in the developing world, particularly where water sources are contaminated by animal urine. Lyme disease, in contrast, is the most common vector-borne illness in the Northern hemisphere.
B. burgdorferi binds to members of a family of receptors on the surface of human cells termed "integrins", which are important in many cellular processes, including inflammation and blood vessel growth. Using a phage display library of B. burgdorferi genomic DNA, we identified a B. burgdorferi protein that mediates bacterial binding to β3-chain integrins, and have defined portions of this protein that participate in integrin recognition. Our current work focuses on determining the role of Borrelia-integrin recognition in the course of infection and the development of Lyme disease in the mouse model. We have also studied the mammalian cell response to B. burgdorferi strains that do or do not express the β3-chain integrin ligand, and by microarray analyses, have identified several signaling/regulatory pathways that show integrin-ligand specific changes in expression. Some of these may be important to the ability of this organism to disseminate from the site of the tick bite to other tissues. We also discovered that another B. burgdorferi protein, BBB07, signals through integrin α3β1 to promote a proinflammatory response in human chondrocytes, which may contribute to the pathogenesis of Lyme arthritis. Our phage display library was also used in vivo to identify B. burgdorferi proteins that bind to vessel walls in specific tissues such as the joint and heart, and further characterization of these proteins is underway.
The goals of the work with Leptospira are to identify mammalian cell surface receptors for these bacteria, and to determine the mammalian cell responses to pathogenic vs. saprophytic Leptospira strains. We have found that pathogenic leptospires bind more efficiently to the cell surface than to the extracellular matrix, and that some of this attachment is mediated by proteoglycans on the mammalian cell. We are currently investigating the nature of additional host receptors, and building a phage display library of Leptospira interrogans DNA to facilitate identification of bacterial proteins that mediate attachment to host cells. Some of the host responses to L. interrogans are reminiscent of those to B. burgdorferi, e.g. those that may facilitate dissemination of the organisms, while other pathways are clearly distinct.
Our ultimate goal is to employ the recent dramatic advances in spirochete genetics to identify new strategies to prevent or treat infection and disease, to identify bacterial and mammalian molecules that contribute to infection and the resulting disease, and to better understand the biology of the organisms in their natural infection cycles.
Recent Publications
Medrano MS, Policastro PF, Schwan TG, Coburn J. Interaction of Borrelia burgdorferi Hbb with the p66 promoter. Nucleic Acids Res. 2010 Jan;38(2):414-27.
Abstract
Breiner DD, Fahey M, Salvador R, Novakova J, Coburn J. Leptospira interrogans binds to human cell surface receptors including proteoglycans. Infect Immun. 2009 Dec;77(12):5528-36.
Abstract
Nelson EJ, Tanudra A, Chowdhury A, Kane AV, Qadri F, Calderwood SB, Coburn J, Camilli A. High prevalence of spirochetosis in cholera patients, Bangladesh. Emerg Infect Dis. 2009 Apr;15(4):571-3.
Abstract
Behera AK, Durand E, Cugini C, Antonara S, Bourassa L, Hildebrand E, Hu LT, Coburn J. Borrelia burgdorferi BBB07 interaction with integrin alpha3beta1 stimulates production of pro-inflammatory mediators in primary human chondrocytes. Cell Microbiol. 2008 Feb;10(2):320-31. Epub 2007 Sep 6.
Abstract
Antonara S, Chafel RM, LaFrance M, Coburn J. Borrelia burgdorferi adhesins identified using in vivo phage display. Mol Microbiol. 2007 Oct;66(1):262-76. Epub 2007 Sep 3.
Abstract
Medrano MS, Ding Y, Wang XG, Lu P, Coburn J, Hu LT. Regulators of expression of the oligopeptide permease A proteins of Borrelia burgdorferi. J Bacteriol. 2007 Apr;189(7):2653-9. Epub 2007 Jan 19.
Abstract
Pinne M, Thein M, Denker K, Benz R, Coburn J, Bergström S. Elimination of channel-forming activity by insertional inactivation of the p66 gene in Borrelia burgdorferi. FEMS Microbiol Lett. 2007 Jan;266(2):241-9.
Abstract
Glickstein LJ, Coburn JL. Short report: Association of macrophage inflammatory response and cell death after in vitro Borrelia burgdorferi infection with arthritis resistance. Am J Trop Med Hyg. 2006 Nov;75(5):964-7.
Abstract
Behera AK, Hildebrand E, Uematsu S, Akira S, Coburn J, Hu LT. Identification of a TLR-independent pathway for Borrelia burgdorferi-induced expression of matrix metalloproteinases and inflammatory mediators through binding to integrin alpha 3 beta 1. J Immunol. 2006 Jul 1;177(1):657-64.
Abstract
Coburn J, Fischer JR, Leong JM. Solving a sticky problem: new genetic approaches to host cell adhesion by the Lyme disease spirochete. Mol Microbiol. 2005 Sep;57(5):1182-95. Review.
Abstract
Craig-Mylius K, Weber GF, Coburn J, Glickstein L. Borrelia burgdorferi, an extracellular pathogen, circumvents osteopontin in inducing an inflammatory cytokine response. J Leukoc Biol. 2005 May;77(5):710-8. Epub 2005 Feb 4.
Abstract
Steere AC, Coburn J, Glickstein L. The emergence of Lyme disease. J Clin Invest. 2004 Apr;113(8):1093-101. Review.
Abstract
Coburn J, Cugini C. Targeted mutation of the outer membrane protein P66 disrupts attachment of the Lyme disease agent, Borrelia burgdorferi, to integrin alphavbeta3. Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):7301-6. Epub 2003 May 14.
Abstract
Cugini C, Medrano M, Schwan TG, Coburn J. Regulation of expression of the Borrelia burgdorferi beta(3)-chain integrin ligand, P66, in ticks and in culture. Infect Immun. 2003 Feb;71(2):1001-7.
Abstract
Coburn J, Medrano M, Cugini C. Borrelia burgdorferi and its tropisms for adhesion molecules in the joint. Curr Opin Rheumatol. 2002 Jul;14(4):394-8. Review.
Abstract
Contact Information
Email: jcoburn@mcw.edu
Phone: 414-955-4116
Room: TBRC C3980