Academic Interests:
Spirochetes are bacteria of major medical importance. Some of the most fundamental aspects of their biology and their mechanisms of pathogenesis are not understood. These medically important bacteria cause syphilis and periodontal disease (Treponema sp.), Lyme disease (Borrelia sp.), leptospirosis (Leptospira sp.), and swine dysentery and human diarrheal disease (Brachyspira sp.). The research in our laboratory is centered on understanding their basic biology using a genetic, biochemical, and structural approach. Our specific area of interest is to have a thorough understanding of spirochete motility, and how this attribute allows the organisms to invade host tissue.
Our current focus is on the Lyme disease spirochete Borrelia burgdorferi. We have taken two separate approaches. First, we characterized in depth their swimming behavior using light microscopy, and with electron cryotomography, their structure. We found that these organisms swim using backward propagating flat waves, much like the waves found in eukaryotic cells such as sperm. In addition, the cryotomography analysis revealed the precise positioning of the periplasmic flagella within the cell, and helped understand the function that these structures play in cell motility. Putting all our results together, we have developed a detailed model of how these organisms swim as a consequence of the rotation of their internal periplasmic flagella.
Our second approach is on the genetics of B. burgdorferi motility. We have identified and characterized most of the genes involved in motility and chemotaxis. These genes involve at least five different operons; one very large operon consisted of 26 genes. Surprisingly, all the motility and chemtoaxis promoters identified were sigma 70-like. This is in marked contrast to what is found in other bacteria. Most bacteria have a hierarchical control of motility gene expression involving specific factors such as sigma-28 that become active at different phases of flagellar assembly. The basis for this difference could be related to the life cycle of this spirochete. B. burgdorferi lives in both mammalian and tick hosts. Perhaps motility and chemotaxis are so vital to B. burgdorferi both in the tick and the mammal that it has evolved a unique control mechanism for flagellar synthesis. Along these lines, we have constructed allelic exchange mutants in specific chemotaxis and motility genes. We found that these organisms are different than most bacteria, as translational rather than transcriptional control plays a major role in motility gene expression. Most recently, we have begun to analyze the role of motility and chemtoaxis in the development of Lyme disease.
Spirochete Videos:
Swimming Borrelia burgdorferi strain 297 under real time and then slow motion taken with 100X darkfield objective
Recent Publications:
Wolgemuth C.W., N.W. Charon. 2005. The kinky propulsion of Spiroplasma (Commentary). Cell.122:827-8. PMID: 16179250.
Charon, N.W. Mycoplasma takes a walk (Commentary). 2005. Proc Natl Acad Sci :102:13713-4. PMID: 16172385
Motaleb, M.A., M.R., Miller, C. Li, R.G. Bakker, S.F. Goldstein, R.E. Silversmith, R.B. Bourret, and N.W. Charon. 2005. 187: 7973-3969. CheX is a CheY-P phosphatase essential for Borrelia burgdorferi chemotaxis. PMID: 16291669
Wolgemuth, C.W., N. W. Charon, S. F. Goldstein, and R. E. Goldstein. 2006.The flagellar cytoskeleton of the spirochetes. J Mol Microbiol Biotechnol. 11:221-227. PMID: 16983197
Bakker, R.G, C. Li, M. R. Miller, C.Cunningham, and N. W. Charon. 2007. Identification of specific chemoattractants and genetic complementation of a Borrelia burgdorferi chemotaxis mutant: A flow cytometry-based capillary tube chemotaxis assay. Appl. and Environ. Microbiol. 73:1180-8. PMID: 17172459
Motaleb, M.A., M.R. Miller, R. G. Bakker, C. Li, and N. W. Charon. 2007. Isolation and characterization of chemotaxis mutants of the Lyme disease spirochete Borrelia burgdorferi using allelic exchange mutagenesis, flow cytometry and cell tracking. Meth. in Enzymol. Two component systems. 422:421-437. PMID: 17628152
Motaleb, M.A., M. R. Miller, C. Li and Nyles W. Charon. 2007. Phosphorylation assays of chemotaxis two-component system proteins in Borrelia. Meth. in Enzymol.. Two component systems, 422:438-447 PMID: 17628153.
Sal, M.S., Chunhao Li, Md. A. Motalab, S. Shibata, S.I-, Aizawa, and N. W. Charon. 2008. Borrelia burgdorferi uniquely regulates its motility genes and has an intricate flagellar hook basal body structure. J. Bacteriol. 190:1912-1921. PMID: 18192386
Wolgemuth, C.W., S. F. Goldstein, and N. W. Charon. 2008. Electron cryotomography reveals novel structures of a recently cultured termite gut spirochete. Molecular Microbiology. 67:1181-1183. PMID: 18221263
Ruby J.D., Lux, R, Shi W., Charon, N.W., Dasanayake A. 2008. Effect of glucose on Treponema denticola cell behavior. Oral Microbiol Immunol. 23:234-8. PMID: 18402610.
Li, C., C, W. Wolgemuth, M. Marko, D. G. Morgan, and N. W.Charon. 2008. Genetic analysis of spirochete flagellin proteins and their involvement in motility, filament assembly, and flagellar morphology. J. Bacteriol. 190: 5706-5615. PMID: 18556797.
Zhou,X. M.R. Miller, M. Motaleb, N.W. Charon, P. He. 2008. Spent culture medium from virulent Borrelia burgdorferi increases permeability of individually perfused microvessels of rat mesentery. PloS One: 3: e4101. PMID: 19116656
Charon, N.W. S. F. Goldstein, M. Marko, C. Hsish, L. L. Gebhardt, M.A. Motaleb, C. W. Wolgemuth, R.J. Limberger, and N. Rowe. 2009. The flat ribbon configuration of the periplasmic flagella of Borrelia burgdorferi and its relationship to motility and morphology. J. Bacteriol. 191:600-607. PMID: 19011030.
Dombrowski, C. W. Kan, M. A. Motaleb, N. W. Charon, R. E. Goldstein, and C. W. Wolgemuth. 2009. The elastic basis for the shape of Borrelia burgdorferi. Biophysical Journal. 96:4409-4417. PMID: 19486665.
Pazy, Y., Motaleb, M. A., Guarnieri, M. T., Charon, N. W., Zhao, R., and Silversmith, R. E.. 2010. Identical phosphatase mechanisms achieved through distinct modes of binding phosphoprotein substrate. Proc. Natl. Acad. Sci. 107:1924-1929. PMID: 20080618.
Li C, Sal M, Marko M, Charon NW. 2010. Differential regulation of the multiple flaqellins in spirochetes. J. Bacteriol. 192:2596-2603: PMID: 20304988.
Chapters in books:
Charon, N.W., S.F. Goldstein, and C. Li. The Beguiling Motility of Treponema. In Molecular Biology and Pathogenesis of Treponema Infection. J. Raldolf and S. Lukehart, 2006. Editors. Caister Academic Press, Norfolk, UK. Chapter 6. pp. 149-147.
Charon, N.W., M. Sal, M.R. Miller, R. Bakker, C. Li, and M. A. Motaleb.2007. Motility gene regulation and chemotaxis in Borrelia burgdorferi. In Molecular Biology of Spirochetes. IOS Press, Washington. pp 42-49.
Goldstein, S.F., C. Li, J. Liu, M.R. Miller, M. A. Motaleb, S. J. Norris, R. E. Silversmith, C. W. Wolgemuth, and N. W. Charon. 2010. The chic motility and chemotaxis of Borrelia burgdorferi. In Borrelia: Molecular Biology, Host Interaction, and Pathogenesis. 2010. D. Scott Samuels and Justin Radolf, Editors. Caister Academic Press, Norfolk, UK. Chapter 7, pp. 167-187.
Awards and Honors:
- MacLachlan Teaching Award
School of Medicine
1981-1982
- Outstanding Teacher Award
West Virginia University.
1982.
- Chair, Gordon Conference on the Biology of Spirochetes
1994.
- West Virginia University Benedum Scholar Award for Research
Biosciences and Health Sciences
1998
- Editorial Board, Journal of Bacteriology
1992-2001
- Fellow of American Academy of Microbiology
2004