Studying mechanisms of extracellular vesicle secretion by protozoan parasites

• Grant number: 19/15909-0
• Support Opportunities: Regular Research Grants
• Duration: April 01, 2020 - June 30, 2022
• Field of knowledge: Biological Sciences - Biochemistry - Biochemistry of Microorganisms
• Convênio/Acordo: Weizmann Institute of Science
• Principal Investigator: Sergio Schenkman
• Grantee: Sergio Schenkman
• Principal researcher abroad: Neta Regev Rudzki
• Institution abroad: Weizmann Institute of Science, Israel
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Ana Claudia Trocoli Torrecilhas ; Dorival Mendes Rodrigues Junior ; Normanda Souza Melo ; Patricia Xander Batista ; Yifat Ofir-Birin

Abstract

Protozoan parasites, which are major human pathogens in both Brazil and Israel, were shown to release extracellular vesicles (EVs) into the host microenvironment, and these are known to modulate the intracellular communication between pathogens and hosts. Although these EVs have been characterized and shown to play important roles in the establishment of infection, specific processes involved in the control of EV release and whether there are different EV sub-populations that act at variable levels are poorly understood. This is particularly important for Kinetoplastidae parasites such as Leishmania sp. and Trypanosoma cruzi, agents of several leishmanioses and Chagas disease, respectively. Our groups at the Federal University of São Paulo and at the Weizmann Institute of Science have been working and collaborating in an effort to characterize EVs in protozoans. In this proposal, we intend to extend our projects to identify the mechanisms and types of EVs secreted by Leishmania and T. cruzi. Based on joint preliminary data and experiments made in other parasitic systems, our first aim will be to generate parasite strains deficient in the expression of candidate proteins of the secretory machinery. This will be achieved by using recently developed CRISPR/Cas9 technology and analyzing the resultant phenotypes for the nature of their EV secretion and infectivity in vitro and in animal models. We have already obtained evidence that different types of EVs are secreted by T. cruzi parasites, and the characterization of the different types of (Leishmania sp. and Trypanosoma cruzi) EVs will be the second aim of this proposal. As a third aim, we will study the effect on EV populations of the generated parasite lines obtained under different conditions to answer how each population is produced. Our major hypothesis is that the type of EV released depends on the mechanism of secretion and that this is regulated by the release of a stimulus and the parasite's life cycle stage. This project complements the ongoing subproject 4 of the Thematic Project "Cell signaling in Trypanosoma during the host-parasite interaction", Process: 2015/22031-0. (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)

VASCONCELOS, CAMILLA IOSHIDA; CRONEMBERGER-ANDRADE, A.; SOUZA-MELO, NORMANDA; MARICATO, JULIANA TERZI; XANDER, PATRICIA; BATISTA, WAGNER LUIZ; SOARES, RODRIGO PEDRO; SCHENKMAN, SERGIO; TORRECILHAS, ANA CLAUDIA. Stress Induces Release of Extracellular Vesicles by Trypanosoma cruzi Trypomastigotes. JOURNAL OF IMMUNOLOGY RESEARCH, v. 2021, SEP 24 2021. (19/15909-0, 20/07870-4, 17/02416-0)

TORRECILHAS, ANA CLAUDIA; SOARES, RODRIGO PEDRO; SCHENKMAN, SERGIO; FERNANDEZ-PRADA, CHRISTOPHER; OLIVIER, MARTIN. Extracellular Vesicles in Trypanosomatids: Host Cell Communication. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 10, DEC 14 2020. (19/15909-0)

JADEL M KRATZ; KAROLINA R GONÇALVES; LAVÍNIA MD ROMERA; CAROLINA BORSOI MORAES; PAULA BITTENCOURT-CUNHA; SERGIO SCHENKMAN; ERIC CHATELAIN; SERGIO SOSA-ESTANI. The translational challenge in Chagas disease drug development. Memórias do Instituto Oswaldo Cruz, v. 117, 2022-05-23. (19/15909-0)