Abstract

Trypanosoma brucei is an extracellular kineotoplastid parasite that causes human African trypanosomiasis (HAT), also known as sleeping sickness. As trypanosomes undergo vector to host transition, heavy transcriptional adaptation such as metabolic shift to glycolysis and upregulated endocytosis occurs. Specifically, glycolysis in the infectious stage becomes the sole source of energy production; thus, the glucose transport mechanism in T. brucei provides one of the most promising therapeutic targets for development of new drugs to treat HAT. Despite an established trypanosome hexose transporter (THT) model for glucose transport across the plasma membrane, there remains gaps in the detailed mechanism of glucose transport especially as it relates to glucose transport across the glycosomal membrane. Using 2-NBDG, a fluorescent glucose analog, we measured glucose uptake rates in the presence of small molecule inhibitors and by using RNA interference (RNAi) to knockdown key proteins to investigate the mechanism of glucose transport in trypanosomes. We have confirmed a direct role of THT in glucose transport of BSF trypanosomes; however, in our investigations, we observed an unexpected ATP-dependence on glucose transport in live trypanosomes, which initiated further study where we focused on the role of endocytosis as an ATP-coupled bulk glucose transport mechanism. Experimental approaches that inhibited endocytosis reduced the observed glucose uptake rate confirming a role for endocytosis-coupled glucose transport in BSF trypanosomes. We provide evidence for an endocytosis-coupled glucose transport mechanism in BSF trypanosomes as an additional and important mechanism that functions in parallel with the established THT model.

Degree

MS

College and Department

Physical and Mathematical Sciences; Chemistry and Biochemistry

Rights

http://lib.byu.edu/about/copyright/

Date Submitted

2018-12-01

Document Type

Thesis

Handle

http://hdl.lib.byu.edu/1877/etd10354

Keywords

Trypanosoma brucei, sleeping sickness, trypanosome hexose transporter, THT, glucose transport, endocytosis

Language

english

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