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Molecular studies on Trypanosoma cruzi and its interaction with cells and factors from the host in vitro and in vivo

Grant number: 06/61450-0
Support type:Research Projects - Thematic Grants
Duration: August 01, 2007 - October 31, 2011
Field of knowledge:Biological Sciences - Parasitology - Protozoology of Parasites
Principal Investigator:José Franco da Silveira Filho
Grantee:José Franco da Silveira Filho
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Co-Principal Investigators:Nobuko Yoshida ; Renato Arruda Mortara
Associated scholarship(s):11/03357-1 - Characterization of the epitopes expression and infectivity of extracellular amastigotes from different Trypanosoma cruzi strains, BP.MS
10/13468-2 - Dual role of Amastin during extracellular amastigotes cell invasion and intracellular multiplication of Trypanosoma cruzi in vitro and in vivo, BP.MS
10/16332-4 - Structure and organization of telomeric and subtelomeric regions of Trypanosoma cruzi, BP.IC
10/13404-4 - Studies of the involviment of a 21 kDa protein in cell invasion in vitro and in vivo by extracellular amastigote form of Trypanosoma cruzi., BP.IC

Abstract

Trypanosoma cruzi, the etiological agent of Chagas' disease, is a highly relevant microorganism from both medical and biological points of view. Although vectorial transmission is mostly under control in the Southern Cone, T cruzi transmission still prevails in Latin America where 15-16 million people are infected. Outbreaks of acute cases of Chagas' disease by oral infection have been reported in different areas of Brazil. Our group has extensively studied host cell invasion by trypomastigotes and amastigotes, an essential step in the establishment of infection in man and other vertebrate hosts. Oral infection has become the focus of our studies in the last years. The mechanisms of in vitro and in vivo T cruzi infection are beginning to be unveiled. Parasite molecules involved in host cell interactions are being analyzed regarding their expression in different developmental forms of T cruzi strains, and also as concerns their genomic organization and structure. In this project we intend to study, at the molecular level, the interaction of T cruzi with host cells and factors both in vitro and in vivo. The project involves the analysis of molecules previously identified by our group as well as the identification and characterization of new molecular and cellular components. Among our objectives is the identification of host cell receptors for the surface proteins of metacycIic trypomastigotes or amastigotes and the study of the intracellular traffic of T cruzi infective forms. We plan to use host cells transfected with different genes as well as co infection models with other trypanosomes and invasive bacteria. Concerning the metacycIic trypomastigote surface antigens, which are mainly encoded by mutagenic families, we intend to identify transcribed and translated genes by hybridizations with DNA micro-arrays and partial sequencing of proteins with mass spectroscopy, respectively. Recombination mechanisms, responsible for the generation of variants in these mutagenic families will be studied in parasites transfected with artificial and specially designed T cruzi chromosomes. These studies will bring new information on the mechanisms controlling gene expression in this parasite and on the evolution of multigenic families. Our project has a multi-disciplinary approach focused on the study of vertebrate host infection by T cruzi. The team of researchers has extensive experience in the fields of molecular and cell Biology, Immunology, Electron and Confocal microscopy and has been working together for many years, in a very productive way, engaged in joint research programmers. With the collaboration of fellow researchers from Brazil and abroad, we intend to make this project succeed. (AU)

Matéria(s) publicada(s) na Agência FAPESP sobre o auxílio:
Malicious invasion 
Malicious invasion 

Scientific publications (7)
(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)
CRUZ, MARIO C.; SOUZA-MELO, NORMANDA; DA SILVA, CLAUDIO VIEIRA; DAROCHA, WANDERSON DUARTE; BAHIA, DIANA; ARAUJO, PATRICIA R.; TEIXEIRA, SANTUZA R.; MORTARA, RENATO A. Trypanosoma cruzi: Role of delta-Amastin on Extracellular Amastigote Cell Invasion and Differentiation. PLoS One, v. 7, n. 12 DEC 18 2012. Web of Science Citations: 19.
CORTEZ, CRISTIAN; MARTINS, RAFAEL M.; ALVES, RENAN M.; SILVA, RICHARD C.; BILCHES, LUCIANA C.; MACEDO, SILENE; ATAYDE, VANESSA D.; KAWASHITA, SILVIA Y.; BRIONES, MARCELO R. S.; YOSHIDA, NOBUKO. Differential Infectivity by the Oral Route of Trypanosoma cruzi Lineages Derived from Y Strain. PLoS Neglected Tropical Diseases, v. 6, n. 10 OCT 2012. Web of Science Citations: 14.
CORTEZ, CRISTIAN; YOSHIDA, NOBUKO; BAHIA, DIANA; SOBREIRA, TIAGO J. P. Structural Basis of the Interaction of a Trypanosoma cruzi Surface Molecule Implicated in Oral Infection with Host Cells and Gastric Mucin. PLoS One, v. 7, n. 7 JUL 31 2012. Web of Science Citations: 20.
MAEDA, FERNANDO YUKIO; ALVES, RENAN MELATTO; CORTEZ, CRISTIAN; LIMA, FABIO MITSUO; YOSHIDA, NOBUKO. Characterization of the infective properties of a new genetic group of Trypanosoma cruzi associated with bats. Acta Tropica, v. 120, n. 3, p. 231-237, DEC 2011. Web of Science Citations: 13.
MARTINS, RAFAEL MIYAZAWA; ALVES, RENAN MELATTO; MACEDO, SILENE; YOSHIDA, NOBUKO. Starvation and rapamycin differentially regulate host cell lysosome exocytosis and invasion by Trypanosoma cruzi metacyclic forms. Cellular Microbiology, v. 13, n. 7, p. 943-954, JUL 2011. Web of Science Citations: 37.
STAQUICINI, DANIELA I.; MARTINS, RAFAEL M.; MACEDO, SILENE; SASSO, GISELA R. S.; ATAYDE, VANESSA D.; JULIANO, MARIA A.; YOSHIDA, NOBUKO. Role of GP82 in the Selective Binding to Gastric Mucin during Oral Infection with Trypanosoma cruzi. PLoS Neglected Tropical Diseases, v. 4, n. 3, p. e613, 2010. Web of Science Citations: 27.
MARTINS, RAFAEL MIYAZAWA; COVARRUBIAS, CHARLES; ROJAS, ROBERT GALVEZ; SILBER, ARIEL MARIANO; YOSHIDA, NOBUKO. Use of L-Proline and ATP Production by Trypanosoma cruzi Metacyclic Forms as Requirements for Host Cell Invasion. Infection and Immunity, v. 77, n. 7, p. 3023-3032, JUL 2009. Web of Science Citations: 46.

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