Date of Award

5-2024

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Microbiology

Committee Chair/Advisor

Dr. Zhicheng Dou

Committee Member

Dr. Jim Morris

Committee Member

Dr. Meredith Morris

Committee Member

Dr. Cheryl Ingram-Smith

Abstract

Toxoplasma gondii is an infectious intracellular parasite that establishes infection within various mammalian hosts, including humans. Toxoplasma infects approximately one-third of the global population, making it an impactful pathogen of study. T. gondii is the causative agent of toxoplasmosis, an opportunistic infection that causes severe illness or fatality in immunocompromised individuals or pregnant women. The parasite possesses a very effective invasion strategy, allowing it to cross different tissue types to disseminate infection across the placental and blood-brain barrier. Although there are a few treatments for acute toxoplasmosis, these drugs can produce adverse side effects. These options are not effective against chronic or congenital toxoplasmosis. In addition, no vaccine has been successfully created against this pathogen. Therefore, identifying parasite-specific drug targets is essential for developing more effective and safe therapeutic options against Toxoplasma infections. This research aimed to understand the molecular mechanisms by which Toxoplasma parasites regulate their energy metabolism during various growth conditions. For example, we studied how parasites incorporate host-derived lactate/pyruvate. These findings suggest the flexibility of T. gondii nutrient metabolism and nutrient acquisition pathways. In addition, this dissertation work investigated the use of novel chemical inhibitors to modulate the energy metabolism of the parasites as a potential therapeutic strategy against toxoplasmosis.

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