Professor of Microbiology, Immunology & Cell Biology Ph.D., University of Minnesota, 1972 2079 Health Science North (Office) (304) 293-4170 (Lab) 2084 Health Science North (Lab) (304) 293-2585 (Lab.) ncharon@hsc.wvu.edu Curriculum Vitae

Academic Interests:

Spirochetes are bacteria of major medical importance. Some of the most fundamental aspects of their biology, or their mechanisms of pathogenesis, are not understood. These medically important bacteria cause syphilis ( Treponema ), Lyme disease ( Borrelia ), leptospirosis ( Leptospira ), swine dysentery and human diarrhea ( Serpulina ) and are associated with periodontal disease. 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 understanding spirochete motility, and how this attribute allows the organisms to invade host tissue.

Our current focus is on Borrelia burgdorferi , which causes Lyme disease, and Serpulina hyodysenteriae , which causes swine dysentery. With respect to B. burgdorferi , we have taken two separate approaches. First, we characterized in depth their swimming behavior using light microscopy, and with high voltage electron- microscopy, 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 electron microscopic analysis allowed us to determine the position of the periplasmic flagella within the cell, and the function that structures play in cell motility. The studies allowed us to develop a detailed model of how these organisms swim as a consequence of the rotation of their internal periplasmic flagella.

Our second approach has been to concentrate on the genetics of B. burgdorferi motility. We have identified and characterized most of the genes involved in motility and chemotaxis. These genes involve four clusters comprising 5 different operons; one very large operon consisted of 26 genes. Suprisingly, all the promoters from the five operons were sigma 70-like. This is in marked contrast to what is found in other bacteria. Most bacteria have a hierarchical control of flagellar synthesis involving specific factors such as sigma 28 which become active at different phases of flagellar assembly. The basis for this difference could be related to the biology of these bacterial species. Perhaps motility and chemotaxis are so vital to Borrelia burgdorferi that it has evolved a unique control mechanism for flagellar synthesis. Our future goals are to construct allelic exchange mutations in specific chemotaxis and motility genes, and to analyze the role of motility in the development of Lyme disease.

The second area of focus, S. hyodysenteriae , centers on the complex structure of its periplasmic flagella, and the role of motility in the disease process. These structures are considerably more complex than the flagella of other bacteria, as they consist of a core surrounded by a protein sheath. We are in the process of analyzing and constructing specific flagellar mutants which have defects in the proteins comprising the core and sheath, and determining the role of these proteins in motility and disease.

Spirochete Videos:

Swimming Borrelia burgdorferi strain 297 under real time and then slow motion taken with 100X darkfield objective

Publications:

Li, C. R. Bakker, M. Motaleb, F. Cabello, M.L. Sartakova, and N.W. Charon . 2002. Asymetrical flagellar rotation in Borrelia burgdorferi non-chemotaxis mutants. Proc. Natl. Acad. Sci. 99:6169-6174.

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

Li, C.H., M. A. Motaleb, M. Sal, S.F. Goldstein, and N.W. Charon . Gyrations, rotations, periplasmic flagella: Chapter 2. The biology of spirochete motility. In "The spirochetes: Molecular and Cellular Biology," 2001.  Horizon Scientific Press, Wymondham, UK.

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

Awards:

• MacLachlan Teaching Award
  School of Medicine
  1981-1982
  
  
• West Virginia University Benedum Scholar Award for Research
  Biosciences and Health Sciences
  1998
  
  
• Fellow of American Academy of Microbiology
  2004