Investigating the involvement of genome lesions and DNA repair in cells infected by Trypanosoma cruzi

• Grant number: 17/01760-0
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): May 01, 2017
• Effective date (End): June 30, 2021
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal researcher: Carlos Frederico Martins Menck
• Grantee: Pilar Sampaio Tavares Veras
• Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 19/19435-3 - The role of DNA damage and mitochondrial function in vascular, immune and neurological ageing (DNA MoVINg), AP.TEM

Abstract

The flagellate protozoan Trypanosoma cruzi is the etiological agent of Chagas disease, of great relevance in Latin America. In the heteroxene life cycle, T. cruzi alternates between stages that present biochemical and morphological differences: replicative forms, epimastigotes (invertebrate host) and amastigotes (mammalian host); and infective forms, metacyclic trypomastigotes, bloodstream trypomastigotes and extracellular amastigotes. It is known that pathological processes such as bacterial, viral and parasitic infections are capable of promoting oxidative stress, generated by the increase of reactive oxygen species (ROS) production in host cell, whose result may be damaging to the host cells or even the pathogen. Major ROS targets in eukaryotic cells include DNA, lipids, proteins and sugars. However, DNA damage formation may result in cell death, and as defense, many DNA damage repair strategies have been developed by cells. The main pathway described in oxidized bases repair is the base excision repair (BER). However, many researchers associate the involvement of more than one DNA repair pathway in the correction of this type of lesion, such as the nucleotide excision repair (NER) pathway. It is known that in response to T. cruzi presence, host cells produce various ROS (O2-, H2O2, ONOO -). It has already been shown that ROS produced during T. cruzi infection induces 8-oxoguanine (8-oxoG) lesions and DNA breaks that signal the activation of poly-adenosine-ribose polymerase 1 (PARP-1). In this project, we intend to characterize the involvement of oxidative stress caused by T. cruzi infection in the formation of genetic damage and in host cell. It is expected that lesions will be generated in the cellular genome during the infection process and that these lesions will impact parasite life cycle. Thus, we believe that studying types of lesions and DNA repair pathways in infected host cells may help to elucidate T. cruzi mechanism of survival and dissemination in vertebrate host. (AU)