Characterization of Nutritional and Oxidative Stress Resistance Mechanisms of Francisella tularensis

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Issue Date
2017
Authors
Worden, Madeline '17
Degree
MS in Molecular Biosciences
Advisor
Malik, Meenakshi
Committee Members
Yager, Eric
LaRocca, Timothy
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Abstract
Francisella tularensis, an intracellular gram negative bacterium, is the causative agent of tularemia. It is classified as a Category A select agent by the Centers for Disease Control (CDC) for being the deadliest agent of biological warfare and bioterrorism. Francisella can grow in diverse environmental conditions in nature, and diverse cell types inside a host. These conditions are extremely stressful and the bacterium has to continually strive hard to acquire nutrients from these nutritionally challenging environments. Major questions in the field of Francisella research that need to be addressed are: 1) what are the mechanisms Francisella employs to counter nutritional stress and alter its growth in these diverse challenging environments? and 2) how does Francisella cope with the oxidative stress? We specifically targeted three genes encoded on the Francisella genome, namely FTL_0283, FTL_0284 and FTL_0285 (relA) to investigate their role in resistance against nutritional and oxidative stress experienced by Francisella. Our overall hypothesis was that \342\200\234FTL_0283, FTL_0284 and FTL_0285 genes of Francisella tularensis play an essential role in nutritional and oxidative stress resistance\342\200\235. The results from the present study demonstrate novel mechanisms adopted by F. tularensis to overcome nutritional and oxidative stress. The FTL_0283, FTL_0284 and FTL_0285 gene products which are contiguously transcribed have an important role under the conditions of nutritional stress due to amino acid or glucose limitation as well as against oxidative stress. It is expected that characterization of such mechanisms would result in the identification of targets for development of effective therapies and vaccines against this extremely virulent bacterial pathogen.
Citation
Worden M. Characterization of nutritional and oxidative stress resistance mechanisms of Francisella tularensis [thesis]. Ann Arbor (MI): Proquest LLC; 2017. 111 p.
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