Biological role of the his catabolism pathway in trypanosomatids

• Grant number: 19/13477-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2019
• End date: December 31, 2020
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Ariel Mariano Silber
• Grantee: Gabriela Torres Montanaro
• 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

Abstract

Trypanosoma cruzi is the etiologic agent of Chagas' disease and is transmitted among mammals by triatomine insects. The fact that this parasite transited between invertebrate and vertebrate hosts resulted in adaptations to different environments, characterized by different nutritional conditions. For example, when glucose is limited in the gut of the vector, T. cruzi can change its metabolism to degrade amino acids. In this context, histidine (His) is an important metabolite for T. cruzi not only because it can be found in the triatomine in high concentrations but also can be used by the parasite to produce ATP. In addition, His can be completely oxidized to CO2 and is able to restore cell viability after severe nutritional stress. The His degradation pathway has four stages in T. cruzi, but is not present in T. brucei, which makes this trypanosomatid a good model for investigating the biological role of the presence of this pathway. In the present project we intend to transfer the complete pathway of His catabolism from T. cruzi to T. brucei, in order to evaluate the phenotypic characteristics acquired by this second parasite when genetically modified in this way. For this, a series of plasmids named pJG was previously developed. The procyclic form of T.brucei will be transfected with the plasmid series pJG, which will allow the constitutive or induced expression of the four enzymes present in the T. cruzi His degradation pathway. Transgenic parasites will be evaluated phenotypically for transport and ability to metabolize His as well as his ability to resist nutritional stress. By observing the complete route of degradation of His in these parasites, it will be possible to determine the evolutionary advantages that this brings to the life cycle of the trypanosomatid and to obtain information that may be of future utility for the development of drugs that interfere in the metabolism of T. cruzi.