The Lyme disease spirochete, Borrelia burgdorferi, exists in two disparate environments (i.e., an arthropod tick vector and mammalian host) during its enzootic life cycle. To effectively adapt to these unique environments, the bacterium alters the expression of numerous genes, including several major outer surface (lipo)proteins that are required for infection and transmission. Transmission of the spirochete from the tick vector to a vertebrate host requires global changes in gene expression that are controlled, in part, by the RpoN/RpoS alternative sigma factor cascade. Rrp2, an enhancer binding protein, was previously described in literature; however, attempts at engineering an Rrp2-deficient strain have failed. In this dissertation we confirm that Rrp2 is essential to spirochete viability in a role independent of the RpoN-RpoS sigma factor cascade. Considering the unique enzootic life cycle of B. burgdorferi, it is not surprising that a large proportion of its genome is composed of hypothetical proteins not found in other bacterial pathogens (499 genes, 38.9% of the genome). We have characterized one such protein, BB0238, and found that it is essential for effective mammalian infection. Finally, analysis of multiple B. burgdorferi strains have identified 160 paralogous families (PFams), and transcriptional analyses of possible RpoS-regulated genes have suggested that a number of these PFams are RpoS-regulated. Most PFam groups in B. burgdorferi contain many paralogs, and potential for functional redundancy can complicate characterization of individual genes' contribution to the infectious cycle via a mutagenesis approach. Herein, we characterize PFam52 through sequential mutagenesis, and we evaluate the paralogs' contribution to mammalian infection. As we better understand the contributions of these proteins to host infection and overcome hindrances specific to the study of the Lyme disease spirochete, we may be able to develop better detection methods, therapeutic interventions, and treatments.
|Commitee:||Edmondson, Ricky, Smeltzer, Mark, Voth, Daniel, Young, Kevin|
|School:||University of Arkansas for Medical Sciences|
|Department:||Microbiology and Immunology|
|School Location:||United States -- Arkansas|
|Source:||DAI-B 76/09(E), Dissertation Abstracts International|
|Keywords:||Bacterial genetics, Borrelia burgdorferi, Lyme disease, Spirochetes, Virulence determinants|
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