The role of Cdc42, RhoA and Rac1 GTPases in actin cytoskeleton during HeLa cell invasion by Trypanosoma Cruzi metacyclic and tissue culture trypomastigotes

• Grant number: 17/24701-9
• Support Opportunities: Scholarships in Brazil - Master
• Start date: April 01, 2018
• End date: July 31, 2019
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Renato Arruda Mortara
• Grantee: Bruno Souza Bonifácio
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 16/15000-4 - Trypanosoma cruzi: intra and interspecific genomic variability and mechanisms of cell invasion/egress, AP.TEM

Abstract

Chagas disease, caused by the flagellate protozoan Trypanosoma cruzi, is considered endemic in the Americas, affecting about 7 million people, with 7,000 deaths per year. T. cruzi presents different evolutionary forms: trypomastigotes (bloodstream and metacyclic), epimastigotes and amastigotes. Trypomastigote is the classic infective form, with the metacyclic originated from insect host able to initiate the infection in mammalian host, and the bloodstream form which sustains the cycle in mammalian host. The cellular invasion by trypomastigotes is complex and involves parasite and host-cell participation, divided into adhesion phase and internalization with the involvement of several molecules and lysosomes resulting in parasite entry. The relation of cellular invasion by trypomastigotes and host-cell actin cytoskeleton has not been fully elucidated, although in the literature there is evidence of interaction between them. The actin cytoskeleton is involved in several functions, including the process of phagocytosis. It is known that the Rho GTPases Cdc42, RhoA and Rac1, are key regulators of actin cytoskeleton. The role of these molecules has been described during cell invasion by T. cruzi extracellular amastigotes promoting induced phagocytosis an important process for extracellular amastigotes invasion. Upon the current controversy over the role of actin cytoskeleton in trypomastigote invasion, the present project aims to evaluate the involvement and control of actin signaling by Rho GTPases in this process. The results could elucidate the molecular mechanisms used by these forms and provide better strategies in the treatment of Chagas disease in future studies. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BONIFACIO, BRUNO SOUZA; BONFIM-MELO, ALEXIS; MORTARA, RENATO ARRUDA; FERREIRA, EDEN RAMALHO. Successful invasion of Trypanosoma cruzi trypomastigotes is dependent on host cell actin cytoskeleton. Journal of Eukaryotic Microbiology, v. 69, n. 3, p. 10-pg., 2022-03-31. (16/16918-5, 17/24701-9, 16/17770-1, 16/15000-4)