Characterization of a Borrelia burgdorferi lipase and eukaryotic-like serine threonine kinase and their roles in Lyme disease pathogenesis : a dissertation /
| Main Author: | |
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| Format: | Thesis Book |
| Language: | English |
| Published: |
[College Station, Tex.] :
[Texas A&M University System Health Science Center],
[2013]
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| Subjects: |
| Abstract: | ABSTRACT: Lyme disease afflicts thousands of people worldwide every year resulting in significant morbidity. The absence of a commercially available vaccine combined with the complications that can arise if Lyme disease is left untreated makes this a significant, emerging disease. The causative agent is the spirochetal bacterium, Borrelia burgdorferi, which is unique from other pathogens in a variety of ways. Particular to this study is the lack of an iron requirement and the unique oxidative assault targets of this bacterium; specifically, lipids containing polyunsaturated acyl groups. An essential player in resistance to oxidative stress is BosR, which was recently shown to also coordinate the expression of essential virulence determinants through RpoS-mediated mechanisms (notably ospC and dbpA). This study describes uncharacterized genes in the three-gene bosR operon, flanking bosR (bb0647). The other linked genes, bb0646 and bb0648, are predicted to encode a lipase and eukaryotic-like serine/threonine kinase, respectively. We show that bb0646 encodes a lipase with a preference for polyunsaturated substrates. This lipase also influences the previously reported hemolytic activity of B. burgodorferi, and is essential for optimal host infectivity. The expected enzymatic activity of the putative eukaryotic-like serine/threonine kinase, BB0648, was not observed however, deletion of this gene in a virulent B. burgdorferi background yielded an unusually elongated phenotype that was lost in a passage-dependent manner. The bb0648 mutant demonstrated global protein and phosphoproteome differences and exhibited an attenuated phenotype when evaluated in a mouse model. Taken together, these results indicate that the genes flanking bosR encode proteins that play important roles in lipid turnover, cellular homeostasis and division, and are required for optimal establishment and persistence of B. burgdorferi during experimental infection. |
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| Item Description: | Vita. "Major Subject: Biomedical Sciences". "Submitted to the Office of Graduate Studies of Texas A&M Health Science Center in partial fulfillment of the requirements for the degree of Doctor of Philosophy May 2013." Approved as to style and content by: Jon T. Skare, Helene Andrews-Polymenis, James Samuel, Paul de Figeiredo |
| Physical Description: | xiii, 183 leaves : illustrations (mostly color) ; 28 cm. |
| Bibliography: | Includes bibliographical references (leaves 163-180). |