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The importance of the L-glutamine and the enzyme glutamine synthetase in the proliferation of bloodstream forms of Trypanosoma brucei and its participation in the VSG biosynthesis

Grant number: 18/22849-1
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): July 01, 2019
Effective date (End): December 31, 2019
Field of knowledge:Biological Sciences - Parasitology - Protozoology of Parasites
Principal researcher:Ariel Mariano Silber
Grantee:Flávia Silva Damasceno
Supervisor abroad: David Mark Carrington
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Research place: University of Cambridge, England  
Associated to the scholarship:17/04808-3 - The relevance of the metabolism of glutamine in the cell biology and bioenergetics of Trypanosoma cruzi and Trypanosoma brucei, BP.PD


Trypanosoma brucei is the causative agent of Human African Trypanosomiasis (HAT), also known as sleeping sickness, a disease with an estimated population of 65 million people at risk in the sub-Saharan Africa. The trypanosomes escape from the mammalian immune response using a population survival strategy to maintain a long-term infection. The cell has a surface coat of a single glycoprotein known as variant surface glycoprotein (VSG). This antigenic variation occurs when a novel VSG gene enters a specialized singular locus, the bloodstream expression site (BES), after a gene conversion event. VSGs are anchored to the cell membranes by the complex glycoconjugate glycosylphosphatidylinositol anchors (GPI) and are usually glycosylated. In the biosynthesis of GPI, the first step is the addition of glucosamine, from a UDP-N-acetylglucosamine (UDP-GlcNAc) donor, to endogenous phosphatidylinositol. Glutamine (Gln) is one of the substrates for the enzyme glutamine:fructose-6-phosphato aminotransferase (GF6PA, EC, the first step of hexosamine biosynthesis pathway, it is our hypothesis that Glutamine could be involved in the biosynthesis of the GPI anchors, which are necessary for VSG expression and switching in the parasite membrane, and therefore, indirectly involved in the main immune evasion mechanism by T. brucei. We are interested in evaluating the role of Gln on the biosynthesis and switching of the VSGs under the hypothesis that a defective Gln biosynthesis could affect both processes by limiting the biosynthesis of their GPI anchors. Remarkably, if we succeed in showing that Gln biosynthesis and uptake are critical for the parasite main mechanism of evasion of the mammalian host immune system, we would be in conditions of proposing it as a candidate to target new drugs for chemotherapy.

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