Date of Award
Doctor of Philosophy (PhD)
Genetics and Biochemistry
James C. Morris, Committee Chair
William R. Marcotte Jr
Kerry S. Smith
Trypanosoma brucei is the protozoan parasite that causes human African trypanosomiasis (HAT, also known as sleeping sickness) and nagana disease in livestock. During its life cycle, trypanosomes occupy niches with very different nutrient contents and immune features. They use glucose solely for ATP production in the mammalian bloodstream while switching to amino acid metabolism in the midgut of the tsetse fly vector. A fast and accurate coordination of gene expression with environment alteration is critical for the successful parasitization of the two hosts. My study focuses on the signaling role of glucose in the development and adaptation of T. brucei. I have found that depletion of glucose triggers very distinct responses in parasites at different life stages. The lack of glucose is lethal to the proliferating long slender bloodstream form, while the absence of the hexose serves as a differentiation cue for the quiescent stumpy bloodstream form. Finally, environments without glucose are favorable for culture of the procyclic form insect stage. My data also suggests the existence of glycolysis independent glucose signaling pathways in T. brucei that may guide the development of parasites by regulating major metabolic pathways. Blood stage parasites have been found to colonize various mammalian tissues besides blood. The consequences of the dynamic glucose concentrations in these tissues on parasite behavior are unresolved. Here, we describe how bloodstream parasites regulate gene expression at the post-transcriptional level in response to the near-absence of glucose. This regulation only occurs when the environmental glucose concentration reaches an extremely low level (<10 μM). We also describe a novel stem-loop structure in the 3’ untranslated region the cytochrome c oxidase subunit VI that is responsible for glucose-depletion-induced translational upregulation.
Qiu, Yijian, "Glucose Sensing in Trypanosoma brucei" (2018). All Dissertations. 2115.