<p> Lyme disease is the most commonly reported vector-borne disease in the United States. The causative agent of Lyme disease, can alter gene expression to enable survival in a diverse set of conditions, including the tick midgut and the mammalian host. External environmental changes can trigger gene expression in <i>B. burgdorferi,</i> and the data demonstrate that <i> B. burgdorferi</i> can similarly alter gene expression as a stress-response when it is treated with the antibiotic doxycycine. After treatment with the minimum bactericidal concentration (MBC) of doxycycline, a subpopulation can alter its phenotype to survive antibiotic treatment, and to host adapt and successfully infect a mammalian host. Furthermore, our data demonstrate that if a population is treated with the MBC of doxycycline, a subpopulation may alter its phenotype to adopt a state of dormancy until the removal of the antibiotic, whereupon the subpopulation can regrow. We demonstrate that the chance of regrowth occurring increases as a population reaches stationary phase, and present a mathematical model for predicting the probability of a persister subpopulation within a larger population, and ascertain the quantity of a persister subpopulation. To determine which genes are expressed as stress-response genes, RNA Sequencing analysis, or RNASeq, was performed on treated, untreated, and treated and regrown <i>B. burgdorferi</i> samples. The results suggest several genes were significantly different in the treated group, compared to the untreated group, and in the untreated and regrown group compared to the untreated group, including a 50S ribosomal stress-response protein, coded from BB_0786. The appendices discuss the theory and methods that were used in RNA Sequencing (RNASeq) analysis, and provide an overview of the database that was created for the <i>B. burgdorferi</i> transcriptome. Additional studies may demonstrate further how persister subpopulations form, and which genes can trigger a persister state in <i>B. burgdorferi.</i></p>
| Identifer | oai:union.ndltd.org:PROQUEST/oai:pqdtoai.proquest.com:3680987 |
| Date | 13 February 2015 |
| Creators | Caskey, John Russell |
| Publisher | Tulane University |
| Source Sets | ProQuest.com |
| Language | English |
| Detected Language | English |
| Type | thesis |
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