Role of motility in Borrelia burgdorferi pathogenesis

Summary

Principal Investigator: Chunhao Li
Abstract: Lyme disease is the most prevalent arthropod bone infection in the United States. The disease, caused by the spirochete Borrelia burgdorferi, is a multiple systemic disorder with various clinical manifestations. In the United States, one of the major manifestations of the acute disease is Lyme arthritis. Approximately 60% of untreated patients develop intermittent attacks of monoarticular or oligoarticular arthritis, primarily in large joints such as knees. Previous studies indicate that B. burgdorferi is highly invasive. These spirochetes traverse the intercellular matrix, penetrate the vascular endothelial cell lining, and finally invade the joints after being deposited in the skin following a tick bite. However, the mechanisms involved in this invasive process is still unknown. The present proposal focuses on the motility of B. burgdorferi, and its role in the disease process. Only recently have the tools for gene targeting been developed for B. burgdorferi, In addition, an understanding of its complex motility is at a very early stage. I hypothesize that the flagellar genes fliG2 and fliG1 play critical but different roles in B. burgdorferi motility. Preliminary results suggest that a fliG1 null mutant continuously swims but is unable to translate (i.e. show displacement), and a fliG2 null mutant is completely non-motile. I also hypothesize that fliG1 functions to coordinate the rotation of the motility organelles, the periplasmic flagella, that allow for directed cell movement. To test these hypotheses, I will characterize these mutants in detail. Green fluorescent protein fusions, and the yeast two hybrid system, will be used to analyze the function of FliG1 and FliG2 in depth. The information obtained should yield a better understanding of molecular mechanisms of B. burgdorferi motility. Second, I hypothesize that motility is a virulence factor. To test this hypothesis, I will target these two genes in a difficult to manipulate virulent strain, analyze the resultant mutants in depth, and test the virulence of these mutants by the mouse model of Lyme disease. I predict that these two mutants will be less virulent than the parental strain. The results obtained will yield critical information on B. burgdorferi motility and and its relationship to virulence. These results could lead to new means of disease prevention and treatment.
Funding Period: 2004-04-19 - 2008-03-31
more information: NIH RePORT

Top Publications

  1. pmc Transcription and genetic analyses of a putative N-acetylmuramyl-L-alanine amidase in Borrelia burgdorferi
    Yu Yang
    Department of Oral Biology, State University of New York at Buffalo, NY 14214 3092, USA
    FEMS Microbiol Lett 290:164-73. 2009
  2. pmc Differential regulation of the multiple flagellins in spirochetes
    Chunhao Li
    Department of Oral Biology, The State University of New York at Buffalo, Buffalo, New York 14214 8031, USA
    J Bacteriol 192:2596-603. 2010
  3. pmc Identification of specific chemoattractants and genetic complementation of a Borrelia burgdorferi chemotaxis mutant: flow cytometry-based capillary tube chemotaxis assay
    Richard G Bakker
    Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 9177, USA
    Appl Environ Microbiol 73:1180-8. 2007
  4. pmc Genetic analysis of spirochete flagellin proteins and their involvement in motility, filament assembly, and flagellar morphology
    Chunhao Li
    Department of Oral Biology, State University of New York at Buffalo, Buffalo, New York 14214, USA
    J Bacteriol 190:5607-15. 2008
  5. pmc Development of a transposon mutagenesis system in the oral spirochete Treponema denticola
    Yu Yang
    Department of Oral Biology, State University of New York at Buffalo, Buffalo, New York 14214, 14214 3092, USA
    Appl Environ Microbiol 74:6461-4. 2008

Scientific Experts

  • Chunhao Li
  • Yu Yang
  • Richard G Bakker
  • Philip E Stewart
  • Xiaoguang Shi
  • Michael R Miller
  • Nyles W Charon
  • Cynthia Cunningham

Detail Information

Publications5

  1. pmc Transcription and genetic analyses of a putative N-acetylmuramyl-L-alanine amidase in Borrelia burgdorferi
    Yu Yang
    Department of Oral Biology, State University of New York at Buffalo, NY 14214 3092, USA
    FEMS Microbiol Lett 290:164-73. 2009
    ..coli. Taken together, these results demonstrate that bb0666 is a homolog of MurNac-LAAs that contributes to the cell division of B. burgdorferi...
  2. pmc Differential regulation of the multiple flagellins in spirochetes
    Chunhao Li
    Department of Oral Biology, The State University of New York at Buffalo, Buffalo, New York 14214 8031, USA
    J Bacteriol 192:2596-603. 2010
    ..The regulatory mechanism identified here should allow spirochetes to change the relative ratio of these flagellin proteins and, concomitantly, vary the stiffness of their flagellar filament...
  3. pmc Identification of specific chemoattractants and genetic complementation of a Borrelia burgdorferi chemotaxis mutant: flow cytometry-based capillary tube chemotaxis assay
    Richard G Bakker
    Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 9177, USA
    Appl Environ Microbiol 73:1180-8. 2007
    ..burgdorferi and the use of flow cytometry for spirochete enumeration. The method should also be useful for assaying chemotaxis for other slow-growing prokaryotic species and in specific environments in nature...
  4. pmc Genetic analysis of spirochete flagellin proteins and their involvement in motility, filament assembly, and flagellar morphology
    Chunhao Li
    Department of Oral Biology, State University of New York at Buffalo, Buffalo, New York 14214, USA
    J Bacteriol 190:5607-15. 2008
    ..Finally, linear elasticity theory indicates that flagellar stiffness directly affects the spirochete's swimming speed...
  5. pmc Development of a transposon mutagenesis system in the oral spirochete Treponema denticola
    Yu Yang
    Department of Oral Biology, State University of New York at Buffalo, Buffalo, New York 14214, 14214 3092, USA
    Appl Environ Microbiol 74:6461-4. 2008
    ..This random mutagenesis system should facilitate research on the biology and pathogenesis of this spirochete, which is associated with human periodontal diseases...