Nyles W. Charon, PhD

Professor Emeritus and Visiting Professor

Organization:

West Virginia University School of Medicine

Department:

Microbiology, Immunology & Cell Biology

Classification:

Clinical Faculty

Charon, N.W. and S.F. Goldstein. 2002. The genetics of motility and chemotaxis of a fascinating group of bacteria: the spirochetes. Ann. Rev. Genetics. 36: 47-73.

Motaleb, M.A. M. Sal, and N.W. Charon.  2004. The decrease in FlaA observed in a flaB mutant of Borrelia burgdorferi is post-transcriptional. J. Bacteriol. 186:3703-11.

Wolgemuth CW, N.W. Charon.  2005. The kinky propulsion of Spiroplasma. Cell.122:827-8.

Charon, N.W. Mycoplasma takes a walk. 2005. Proc. Natl. Acad. Sci.102:13713-4.

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. CheX is a CheY-P phosphatase essential for Borrelia burgdorferi chemotaxis . J. Bacteriol. 187: 7973-3969.

C. W. Wolgemuth, N. W. Charon, S. F. Goldstein, and R. E. Goldstein. 2006.The flagellar cytoskeleton of the spirochetes. J. Mol. Microbiol. Biotechnol. 11: 221-7.

R. G. Bakker, C. Li, M. R. Miller, C. Cunningham, and N. W. Charon. 2006. 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

Md. A. Motaleb, 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. Methods in Enzymology. Two component systems. 422:421-437.

Md. A. Motaleb, M. R. Miller, C. Li and N.W. Charon. 2007. Phosphorylation assays of chemotaxis two-component system proteins in Borrelia. Methods in Enzymology. Two component systems. 422:438-447.

Wolgemuth, C.W., S. F. Goldstein, and N. W. Charon. 2008. Electron cryotomography reveals novel structures of a recently cultured termite gut spirochete. Mol. Microbiol. 67:1181-1183.

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

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.

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.

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.

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.

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.

Pazy, Y., M.A. Motaleb, M.T. Guarnieri, N.W. Charon, R. Zhao, and R.E. Silversmith. 2010. Identical phosphatase mechanisms achieved through distinct modes of binding phosphoprotein substrate. Proc. Natl. Acad. Sci. 107:1924-1929.

Li C., M. Sal.  M. Marko, N.W.  Charon.  2010. Differential regulation of the multiple flaqellins in spirochetes. J. Bacteriol. 192:2596-2603 8

Xu H., G. Raddi G., J. Liu, N.W. Charon, and C. Li.  2011.Chemoreceptors and flagellar motors are subterminally located in close proximity at the two cell poles in spirochetes. J. Bacteriol. 193::2652-6.

Motaleb, Md. A, S.Z. Sultan, M. R. Miller, C. Li, and N. W. Charon. 2011. CheY3 of Borrelia burgdorferi is the key response regulator essential for chemotaxis and forms a long-lived phosphorylated intermediate. J Bacteriol. 193:3332-41.

Sze, C.W., D.R. Morado, J. Liu, N.W. Charon, H. Xu, C. Li.  2011, Carbon storage regulator A( CsrA (Bb) ) is a repressor of Borrelia burgdorferi flagellin protein FlaB. Mol. Microbiol. 82: 851-864.PMID 21999436.

Lambert, A., N. Takahshi, N.W. Charon, and M. Picardeau. 2012. Chemotactic behavior of pathogenic and non-pathogenic Leptospira species. Appl. Environ. Microbiol.78: 8467- 69. PMID 23001652.

Zhang K, J. Liu, Y. Tu,  H. Xu, N.W. Charon, and C. Li. 2012. Two CheW coupling proteins are essential in a chemosensory pathway of Borrelia burgdorferi. Mol. Microbiol. 85:782-94. PMID:22780444.

Charon, N.W., A. Cockburn, C. Li, J. Liu, K. Miller, M. Miller, M. Motaleb, and C. Wolgemuth. 2012. The unique paradigm of spirochete motility and chemotaxis. Ann. Rev. Microbiol. 66:349-370. PMID 22994496.

Sultan S.Z., A. Manne, P.E. Stewart, A. Bestor, P.A. Rosa, N.W. Charon, and M.A. Motaleb. 2013. Motility is crucial for the infectious life cycle of Borrelia burgdorferi. Infect. Immun. 81:2012-21.PMID 23529620.

Zhao X., K. Zhang, T. Boquoi, B. Hu, M.A. Motaleb, K.A. Miller, M.E. James ME, N.W. Charon, M.D. Manson, S.J. Norris, C. Li, and J. Liu J.2013. Cryoelectron tomography reveals the sequential assembly of bacterial flagella in Borrelia burgdorferi. Proc. Natl. Acad. Sci. 110: 13490-5. PMID:23940315.

Miller KA, Motaleb MA, Liu J, Hu B, Caimano MJ, Miller MR, Charon NW. Initial characterization of the FlgE hook high molecular weight complex of Borrelia burgdorferi. PLoS One. 2014 May 23;9(5):e98338. doi: 10.1371/journal.pone.0098338. eCollection 2014 May 23. PMID:24859001

Miller MR, Miller KA, Bian J, James ME, Zhang S, Lynch MJ, Callery PS, Hettick JM, Cockburn A, Liu J, Li C, Crane BR, Charon NW. Spirochaete flagella hook proteins self-catalyse a lysinoalanine covalent crosslink for motility. Nat Microbiol. 2016 Aug 8;1(10):16134. doi: 10.1038/nmicrobiol.2016.134.PMID:27670115

Wunder E.A., C.P. Figueira, N. Benaroudj, B. Hu, B.A. Tong, F. Trajtenberg , J. Liu, M.G. Reis, N.W. Charon, A. Buschiazzo, M. Picardeau M, A. Ko. 2016. A novel flagellar sheath protein, FcpA, determines filament coiling, translational motility and virulence for the Leptospira spirochete. Mol Microbiol. 101:457-70. doi: 10.1111/mmi.13403

Kumar, B. K. A. Miller, N.W. Charon, J. Legleiter. Periplasmic flagella in Borrelia burgdorferi function to maintain cellular integrity upon external stress. PLOS One, September 12, 2017. https://doi.org/10.1371/journal.pone.0184648.

http://bit.ly/2fw9FhS.

Lynch MJ, Miller M, James M, Zhang S, Zhang K, Li C, Charon NW, Crane. 2019. Nat Chem Biol 15, 959–965. . PMID: 31406373.

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

School of Medicine Dean's Excellence Award in Research

2006

 

Media

 

http://medicine.hsc.wvu.edu/micro/People/Faculty/Nyles-Charon

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. By analyzing specific motility and chemotaxis mutants, we and our colleagues have shown that motiity and chemotaxis are essential for B. burgdorferi to bring disease to the host. 

Our newest project is quite exciting: We are analyzing a unique attribute of spirochetes that may lead to a new means of treatment of spirochete diseases. In flagellated bacteria, the hook region of the flagella, which serves as a universal joint linking the membrane imbedded motor to the flagella, is made up of FlgE proteins. These proteins form a tubular structure that are held together by electrostatic and hydrophobic bonds. In contrast, in all species of spirochetes tested, these proteins are bonded together covalently, and we have found that it is a unique amino acid lysinoalanine that forms the cross-link. Mutants that are unable to form the lysinoalanine cross-link were deficient in motility.  In addition, we were able to catalyze the formation of the cross-link in vitro. We are in the process of screening for compounds that inhibit this cross-linking.  These compounds may well serve as a potential drug for the treatment of spirochete diseases.