Influence of Enzyme Deacetylation on the Metabolism of Trypanosoma cruzi

• Grant number: 23/15330-8
• Support Opportunities: Research Grants - Visiting Researcher Grant - International
• Start date: July 01, 2024
• End date: July 31, 2024
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Ariel Mariano Silber
• Grantee: Ariel Mariano Silber
• Visiting researcher: Esteban Serra
• Visiting researcher institution: Universidad Nacional De Rosario/Unr, Argentina
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 21/12938-0 - Amino acid metabolism in Trypanosoma cruzi: a toolbox to survive in hostile environments, AP.TEM

Abstract

Chagas Disease, also known as American Trypanosomiasis, is a significant public health concern in the Americas. It is caused by Trypanosoma cruzi, a protozoan parasite, and is endemic in numerous countries, with potential for global spread due to migrations and alternative transmission routes. The current treatment options have limitations in terms of efficacy and side effects. Consequently, there is a critical need to identify novel trypanocidal compounds effective across all disease stages. This research project is focused on gaining a comprehensive understanding of the hypothesized role of protein acetylation, on the regulating the energy metabolism of T. cruzi. Specifically, it will investigate the impact of acetylation, deacetylation, and the binding of acetylated metabolic enzymes recognized by bromodomain-containing proteins. The project aims to elucidate the mechanisms through which acetylation influences the biology of T. cruzi and its adaptation to varying environments. For this, we will use three already obtained lineages of T. cruzi expressing sirtuins (cytosolic Sir2rp1 and mitochondrial Sir2rp3) and a glycosomal bromodomain-containing factor (TcBDF1) to analyze mitochondrial energy metabolism, and to assess the production of reactive oxygen species (ROS) under the over-expression of these proteins. This collaboration leverages the combined expertise of both research groups to advance the knowledge on T. cruzi biology, particularly in relation to acetylation and its potential as a target for the development of novel antiparasitic drugs. (AU)