Professor of Microbiology, Immunology and Cell Biology
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.
School of Medicine
West Virginia University.
Biosciences and Health Sciences