The relevance of the metabolism of glutamine in the cell biology and bioenergetics of Trypanosoma cruzi and Trypanosoma brucei

• Grant number: 17/04808-3
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date until: November 01, 2017
• End date until: October 31, 2021
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Ariel Mariano Silber
• Grantee: Flávia Silva Damasceno
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 16/06034-2 - The biological role of amino acids and their metabolites in Trypanosoma cruzi, AP.TEM
• Associated scholarship(s): 18/22849-1 - 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, BE.EP.PD

Abstract

The Trypanosoma cruzi is a causative agent of Chagas disease, also known as American tripanosomise. The Trypanosoma brucei is etiological agent of sleeping sickness also known as Africa tripanosomiase. T. cruzi is able to utilize carbohydrate and amino acids as carbon and energy source. The participation of amino acid in important biological process as proliferation, differentiation, cell invasion, and stress conditions resistance has been described. The importance of amino acids for Trypanosoma brucei has been described in procyclic forms, but little is known about bloodstream forms. Procyclic forms developed a metabolism based on consumption of amino acids as proline. Has been described that proline metabolism is essential for the parasite survival in the invertebrate host. The amino acid metabolism occurs with the production of NH4+. These parasites do not have the functional urea cycle, the ammonia may be excreted into the extracellular medium, or it can be transferred to ±-ketoglutarate forming glutamate, which acts as a donor of NH3 to pyruvate, forming alanine, a major product of amino acid metabolism. The synthesis of glutamine has glutamate and ammonia as substrates, this reaction is catalyzed by the enzyme glutamine synthetase, which can be involved in the ammonia detoxification in these parasites. The Glutamine may be a substrate for important pathways to parasite survival such as synthesis of pyrimidines, amino sugars, and GMP. The main goal of this project is to evaluate the relevance of the metabolism of glutamine in the cell biology and bioenergetics of Trypanosoma cruzi and Trypanosoma brucei using the CRISPR/cas9 to GS gene knockout in T. cruzi and RNAi to induce GS knockdown in T. brucei.