Lyme disease is the leading tick-borne bacterial disease in the world resulting in greater than 30,000 cases per year in the US alone. Lyme disease is caused by tick-bite transmission of the pathogenic spirochete Borrelia burgdorferi. An increased understanding of the molecular mechanisms that B. burgdorferi uses to survive throughout its infectious cycle is critical for the development of innovative diagnostic and therapeutic protocols to reduce the incidence of Lyme disease. One of the major difficulties blocking this effort has been genome-wide identification of the B. burgdorferi genes that are expressed in the mammalian host environment. Using in vivo expression technology (IVET) in B. burgdorferi for the first time we have identified B. burgdorferi genes that are expressed during an active mammalian infection. The in vivo-expressed candidate genes putatively encode proteins in various functional categories including antigenicity, metabolism, motility, nutrient transport and unknown functions.
In addition to identifying promoters corresponding to annotated genes, our screen has identified in vivo-expressed transcripts that map within genes and on the antisense strand relative to annotated genes. We predict that some of these DNA sequences may represent promoters for regulatory RNAs. Research in our laboratory is directed at understanding B. burgdorferi infection mechanisms through genetic, biochemical and in vivo analyses of unique in vivo-expressed genes. Furthermore, because accurate diagnosis is currently the greatest challenge for the clinical management of Lyme disease my lab is focused on development of a simplified, objective and sensitive approach for the detection of B. burgdorferi antibodies in infected patients.
- Halpern MD, Molins CR, Schriefer M and Jewett MW. 2014. Simple objective detection of human Lyme disease infection using immuno-PCR and a single recombinant hybrid antigen. Clin Vaccin Immunol, 21(8):1094-105.
- Ellis TC, Jain S, Linowski A, Rike K, Bestor A, Rosa PA, Halpern M, Kurhanewicz S and Jewett MW. 2013. In vivo expression technology identifies a novel virulence factor critical for Borrelia bugdorferi persistence in mice. PLoS Pathogens, 29 Aug 2013, 10.1371/journal.ppat.1003567.
- Halpern MD, Jain S and Jewett MW. 2013. Enhanced detection of host response antibodies to Borrelia burgdorferi using immune-PCR. Clin Vaccine Immunol, 9 Jan 2013 doi:10.1128/CVI.00630-12 [epub ahead of print].
- Chen HD, Jewett MW and Groisman EA. 2012. An allele of an ancestral transcription factor dependent on a horizontally acquired gene product. PLoS Genetics, Dec;8(12):e1003060. doi: 10.1371/journal.pgen.1003060. Epub 2012 Dec 27.
- Jain S, Sutchu S, Rosa PA, Byram R, Jewett MW. Borrelia burgdorferi harbors a transport system essential for purine salvage and mammalian infection. Infect Immun. 2012 Jun 18. [Epub ahead of print]
- Jewett MW, Jain S, Linowski AK, Sarkar A and Rosa PA. 2011. Molecular characterization of the Borrelia burgdorferi in vivo essential protein, PncA. Microbiology, 157(10):2831-2840.
- Chen HD, Jewett MW and Groisman EA. 2011. Ancestral genes can control the ability of horizontally-acquired loci to confer new traits. PLoS Genetics, Jul;7(7):e1002184. Epub 2011 Jul 21.
- Hayes BM, Jewett MW, Rosa PA. 2010. A lacZ reporter system for use in Borrelia burgdorferi. Appl. Environ. Microbiol. 76(22):7404-12.
- Bestor A, Stewart PE, Jewett MW, Sarkar A, Tilly K and Rosa PA. 2010. Using the Cre-lox recombination system to investigate lp54 gene requirement in the infectious cycle of Borrelia burgdorferi. Infect. Immun. 78(6):2397-407.
- Jewett MW1, Lawrence K, Bestor A, Byram R, Gherardini F and Rosa PA. 2009. GuaA and GuaB are essential for B. burgdorferi survival in the tick-mouse infectious cycle. J. Bacteriol. 191(20):6231-6241.
- Lawrence K, Jewett MW, Rosa PA, Gherardini F. 2009. Borrelia burgdorferi bb0426 encodes a 2′-deoxyribosyltransferase that plays a central role in purine salvage. Mol. Microbiol., 72(6):1517-1529.
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