The bacterial pathogen responsible for Lyme disease ¬— Borrelia burgdorferi— is an atypical Gram-negative spirochete that is transmitted to humans via the bite of an infected Ixodes tick. Like all Gram-negative bacteria the structural portion of the cell envelope known as peptidoglycan (PG) is sandwiched between the inner and outer membranes. Unlike virtually all bacteria, this PG layer is unique in B. burgdorferi in that the amino acid structure differs from most Gram-negative and Gram-positive bacteria by the addition of an Ornithine residue to the third amino acid location in the crosslinking structure. This unique motif is hypothesized to be responsible for the unusual clinical manifestations seen in Lyme disease, specifically Lyme arthritis, the most common late stage symptom of the disease in the United States. Peptidoglycan is only one component of the cell envelope in B. burgdorferi though; other portions of the cell envelope remain understudied specifically when viewed through the lens of the immune response they may elicit in addition to that of PG. The combined immunological effect of the unique bacterial antigen found in B. burgdorferi PG, as well as other potentially associated proteins contained within the cell wall, are explored here. These studies further our understanding of the B. burgdorferi cell envelope and provide critical information that underlies the elusive pathogenesis of Lyme disease. / Master of Science in Life Sciences / Lyme disease is a growing health concern, namely for the countries in the Northern Hemisphere. The bacterium responsible for this illness is Borrelia burgdorferi. B. burgdorferi can survive in the human body and is a threat in that as it replicates in the human host, it sheds pro-inflammatory fragments of its unique cell wall into the environment. This thesis will explore the consequences of this cell wall shedding and how the human immune response differs from the response seen in other more common bacteria. Additionally, I have found that the cell envelope fragments shed from B. burgdorferi may contain more than meets the eye. There is evidence here to support the discovery of a moonlighting protein that is bound to a portion of the cell wall in B. burgdorferi. This protein acts to bolster the structural integrity of the cell while also acting to modulate the host immune response.
| Identifer | oai:union.ndltd.org:VTETD/oai:vtechworks.lib.vt.edu:10919/98522 |
| Date | 21 May 2020 |
| Creators | Davis, Marisela Martinez |
| Contributors | Biochemistry, Jutras, Brandon L., Jones, Caroline N., Tu, Zhijian Jake |
| Publisher | Virginia Tech |
| Source Sets | Virginia Tech Theses and Dissertation |
| Detected Language | English |
| Type | Thesis |
| Format | ETD, application/pdf, application/pdf |
| Rights | In Copyright, http://rightsstatements.org/vocab/InC/1.0/ |
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