Lyme disease, caused by the spirochete Borrelia burgdorferi, is the most prevalent vector-borne disease in the United States and Europe. Recently the CDC estimated that approximately 300,000 Americans are infected with B. burgdorferi annually, which is 10 times greater than the annual estimates for the past 10 years. Unfortunately, there are no available vaccines to prevent Lyme disease. Bacteria are transmitted to vertebrates through the bite of infected Ixodes sp. ticks, and the untreated infection often develops into debilitating carditis, arthritis, and neurological manifestations. Therefore, it is important to identify genes critical for mammalian infection in efforts to identify potential targets for vaccine development and/or therapeutic drug treatment. In this dissertation, we identified three lysine residues (e.g. K82, K163, and K170) in a known virulence determinant, decorin-binding protein A (DbpA), that potentiate B. burgdorferi infection by mediating the interaction of DbpA with decorin and dermatan sulfate instead of altering the overall structure of DbpA or localization of the adhesin within the bacterial cell. Since the bacterium must regulate the transcription of genes to survive within its complex enzootic life cycle, it is not surprising that a number of putative transcriptional regulators have not been identified. We have characterized a conserved protein, BB0345, which might function as a transcriptional regulator due to the presence of an N-terminal helix-turn-helix domain. We found that BB0345 is required by B. burgdorferi for mammalian infectivity by potentially aiding the survival of the bacterium in vivo. Together, these findings contribute greatly to our understanding of how B. burgdorferi utilizes genetic components to promote mammalian virulence.
|Commitee:||Boehme, Karl, Ponnappan, Usha, Tackett, Alan, Young, Kevin|
|School:||University of Arkansas for Medical Sciences|
|Department:||Microbiology and Immunology|
|School Location:||United States -- Arkansas|
|Source:||DAI-B 77/09(E), Dissertation Abstracts International|
|Subjects:||Entomology, Microbiology, Biochemistry, Immunology|
|Keywords:||Borrelia burgdorferi, Pathogenesis|
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