The role of arginine transport in the stress response and differentiation of Trypanosoma cruzi

• Grant number: 22/15997-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2023
• End date: December 31, 2024
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Sergio Schenkman
• Grantee: Gabriella Luisa Pasini Moraes
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 20/07870-4 - Mechanisms of trypanosomatid adaptation to hosts through the control of transcription, protein synthesis and secretion of extracellular vesicles, AP.TEM

Abstract

The parasitic protozoan Trypanosoma cruzi, the agent of Chagas disease that affects the human population, adapts to different environments as it can develop in the digestive tract of the vector insect and its mammalian hosts. The identification of the mechanisms that lead to these adaptations may be useful in the development of strategies and medications for the treatment of this disease, which is still very limited. Recently, through selection to resistance to hygromycin, a protein synthesis inhibitor, we generated a mutant which has not been able to differentiate into infectious forms. At the same time, this parasite is no longer competent for endociting macromolecular nutrients. Genomic sequencing showed a significant loss of a tandem of identical genes encoding for a cationic transporter capable described as the transporter of the amino acid arginine. Unlike many organisms, T. cruzi os is capable of phosphorylate arginine as an alternative source of energy, useful in situations of lack of nutrients. Thus, we intend in this project a) To verify whether the incorporation of arginine is reduced in the mutant, b) detect the expression levels of total messenger and RNA associated with polysomes in the mutant, d) Restore gene expression, c) Perform gene removal in the wild type lineage. In this way we can verify whether the receptor and/or arginine transporter has an impact on the differentiation and endocytosis pathways of the parasite, allowing us to understand how this would be related to the adaptive responses of the parasite to new conditions in the different hosts.