Molecular and cellular biology of the parasitism by Trypanosoma cruzi

• Grant number: 11/51475-3
• Support Opportunities: Research Projects - Thematic Grants
• Start date: March 01, 2012
• End date: May 31, 2016
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: José Franco da Silveira Filho
• Grantee: José Franco da Silveira Filho
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Pesquisadores principais: Nobuko Yoshida ; Renato Arruda Mortara
• Associated scholarship(s): 16/04367-4 - Functional and structural characterization of KKT2 and KKT9 kinetochore proteins of Trypanosoma Cruzi, BP.IC; 15/21969-5 - Study of host cell co-infection with two strains of Trypanosoma Cruzi, BP.IC; 15/14942-3 - Identification of homologous and orthologous genes of the multigene family SAP in Trypanosoma cruzi strains and other species of the clade Trypanosoma cruzi, BP.IC; + associated scholarships 14/22663-4 - Establishment of molecular karyotype and syntenic relationships of bat trypanosomes from Trypanosoma Cruzi clade, BP.MS; 14/21338-2 - In situ evaluation of acute and chronic infection with Trypanosoma cruzi trypomastigotes (TCI and TcVI) in BALB/c and C57BL/6 inbred mice, BP.MS; 12/23150-5 - Structural and functional characterization of the glycoprotein Ssp-4 of amastigotes forms from Trypanosoma cruzi, BP.DD; 13/04249-3 - Study of protein kinases pathways involved in the invasion process of HeLa cells by Trypanosoma cruzi extracellular amastigotes (EAs), BP.IC; 13/04372-0 - Comparative study of telomeric and subtelomeric regions of Trypanosoma cruzi, BP.DD; 12/25282-6 - The role of ezrin, radixin and moesin (ERM proteins) in cell invasion by extracellular amastigotes of Trypanosoma cruzi., BP.DR; 13/02570-9 - Ionizing radiation effect on Trypanosoma cruzi chromosomal organization, BP.IC; 12/21335-8 - The Cdc42/N-WASP and Rac1/WAVE2 pathways regulation of actin dynamics during cellular invasion by extracellular amastigotes of Trypanosoma cruzi, BP.DR; 12/21713-2 - Molecular karyotyping and chromosomal evolution in Trypanosoma cruzi: analysis syntenic among isolates from different parasite strains, BP.IC; 11/06653-0 - Structure and organization of telomeric and subtelomeric regions of Trypanosoma cruzi, BP.PD; 10/19335-4 - Experimental study on the mechanisms of fusion between heterotypic Leishmania spp. parasitophorous vacuoles, BP.PD - associated scholarships

Abstract

Trypanosoma cruzi is the causative agent of Chagas' disease that affects 15-16 million people in America. Vectorial transmission of T. cruzi still occurs in several regions. Migration from endemic areas to developed countries has led to new cases in the US, Europe, Japan and Australia. Since Triatoma infestans has been controlled and transmission by blood transfusion, halted, oral infection is admittedly the most important route for T. cruzi acquisition. Aiming at the clarification of mammalian cell invasion and colonization by T. cruzi mechanisms that have only been partially elucidated, we intend to identify cellular and molecular components, signaling pathways both in the host cell and parasite, using different parasite forms, transgenic animals and cells with altered expression of relevant proteins as well as parasites expressing variant forms of the known T. cruzi molecules involved in invasion and colonization. T. cruzi consists of genetically heterogeneous populations that differ both in genotypic aspects and phenotypic adaptations and virulence towards the mammalian host. Here we propose to perform comparative caryotype and chromosome extremities analyses of distinct T. cruzi lineages and other mammalian trypanosomatids, including chromosome evolution studies. This is a multitask project put forward by scientists with renown experience in Protozoology with emphasis in Cellular and Molecular Biology. The researchers collaborate for many years in a highly productive fashion and with the aid of colleagues both in Brazil and abroad, we intend to contribute to the advance in the proposed areas. (AU)

Scientific publications

(22)

(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)

MARTINS, NADINI OLIVEIRA; DE SOUZA, RENATA TORRES; CORDERO, ESTEBAN MAURICIO; MALDONADO, DANIELLE CORTEZ; CORTEZ, CRISTIAN; MARINI, MARJORIE MENDES; FERREIRA, EDEN RAMALHO; BAYER-SANTOS, ETHEL; DE ALMEIDA, IGOR CORREIA; YOSHIDA, NOBUKO; et al. Molecular Characterization of a Novel Family of Trypanosoma cruzi Surface Membrane Proteins (TcSMP) Involved in Mammalian Host Cell Invasion. PLoS Neglected Tropical Diseases, v. 9, n. 11, NOV 2015. (11/51475-3)

ANGEL CHIURILLO, MIGUEL; CORTEZ, DANIELLE R.; LIMA, FABIO M.; CORTEZ, CAROLINE; LUIS RAMIREZ, JOSE; MARTINS, ANDRE G.; SERRANO, MYRNA G.; TEIXEIRA, MARTA M. G.; DA SILVEIRA, JOSE FRANCO. The diversity and expansion of the trans-sialidase gene family is a common feature in Trypanosoma cruzi clade members. INFECTION GENETICS AND EVOLUTION, v. 37, p. 266-274, JAN 2016. (11/51475-3)

MAEDA, FERNANDO YUKIO; CORTEZ, CRISTIAN; IZIDORO, MARIO AUGUSTO; JULIANO, LUIZ; YOSHIDA, NOBUKO. Fibronectin-Degrading Activity of Trypanosoma cruzi Cysteine Proteinase Plays a Role in Host Cell Invasion. Infection and Immunity, v. 82, n. 12, p. 5166-5174, DEC 2014. (11/51475-3)

BONFIM-MELO, ALEXIS; FERREIRA, EDEN R.; MORTARA, RENATO A.. Rac1/WAVE2 and Cdc42/N-WASP Participation in Actin-Dependent Host Cell Invasion by Extracellular Amastigotes of Trypanosoma cruzi. FRONTIERS IN MICROBIOLOGY, v. 9, FEB 28 2018. (11/51475-3, 12/21335-8)

FERREIRA, EDEN RAMALHO; HORJALES, EDUARDO; BONFIM-MELO, ALEXIS; CORTEZ, CRISTIAN; DA SILVA, CLAUDIO VIEIRA; DE GROOTE, MICHEL; PASCHOAL SOBREIRA, TIAGO JOSE; CRUZ, MARIO COSTA; LIMA, FABIO MITSUO; CORDERO, ESTEBAN MAURICIO; et al. Unique behavior of Trypanosoma cruzi mevalonate kinase: A conserved glycosomal enzyme involved in host cell invasion and signaling. SCIENTIFIC REPORTS, v. 6, APR 26 2016. (11/51475-3)

BAYER-SANTOS, ETHEL; MARINI, MARJORIE M.; DA SILVEIRA, JOSE F.. Non-coding RNAs in Host-Pathogen Interactions: Subversion of Mammalian Cell Functions by Protozoan Parasites. FRONTIERS IN MICROBIOLOGY, v. 8, MAR 21 2017. (11/51475-3, 15/25381-2)

FERREIRA, BIANCA LIMA; FERREIRA, EDEN RAMALHO; BONFIM-MELO, ALEXIS; MORTARA, RENATO ARRUDA; BAHIA, DIANA. Trypanosoma cruzi extracellular amastigotes selectively trigger the PI3K/Akt and Erk pathways during HeLa cell invasion. Microbes and Infection, v. 21, n. 10, p. 485-489, DEC 2019. (13/04249-3, 11/51475-3)

COSTA, RENATA WATANABE; DA SILVEIRA, JOSE F.; BAHIA, DIANA. Interactions between Trypanosoma cruzi Secreted Proteins and Host Cell Signaling Pathways. FRONTIERS IN MICROBIOLOGY, v. 7, MAR 31 2016. (11/51475-3)

BAYER-SANTOS, ETHEL; LIMA, FABIO MITSUO; RUIZ, JERONIMO CONCEICAO; ALMEIDA, IGOR C.; DA SILVEIRA, JOSE FRANCO. Characterization of the small RNA content of Trypanosoma cruzi extracellular vesicles. Molecular and Biochemical Parasitology, v. 193, n. 2, p. 71-74, FEB 2014. (11/51475-3)

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. (11/51475-3, 06/61450-0)

FLORENTINO, PILAR T. V.; REAL, FERNANDO; ORIKAZA, CRISTINA M.; DA CUNHA, JULIA P. C.; VITORINO, FRANCISCA N. L.; CORDERO, ESTEBAN M.; SOBREIRA, TIAGO J. P.; MORTARA, RENATO A.. A Carbohydrate Moiety of Secreted Stage-Specific Glycoprotein 4 Participates in Host Cell Invasion by Trypanosoma cruzi Extracellular Amastigotes. FRONTIERS IN MICROBIOLOGY, v. 9, APR 10 2018. (12/23150-5, 11/51475-3)

MACEDO, SILENE; FERREIRA RODRIGUES, JOAO PAULO; SCHENKMAN, SERGIO; YOSHIDA, NOBUKO. Beta-adrenergic antagonist propranolol inhibits mammalian cell lysosome spreading and invasion by Trypanosoma cruzi metacyclic forms. Microbes and Infection, v. 19, n. 4-5, p. 295-301, APR-MAY 2017. (11/51475-3)

PESSOA, CARINA CARRARO; FERREIRA, EDEN RAMALHO; BAYER-SANTOS, ETHEL; RABINOVITCH, MICHEL; MORTARA, RENATO ARRUDA; REAL, FERNANDO. Trypanosoma cruzi Differentiates and Multiplies within Chimeric Parasitophorous Vacuoles in Macrophages Coinfected with Leishmania amazonensis. Infection and Immunity, v. 84, n. 5, p. 1603-1614, MAY 2016. (11/51475-3, 10/19335-4)

CORTEZ, CRISTIAN; REAL, FERNANDO; YOSHIDA, NOBUKO. Lysosome biogenesis/scattering increases host cell susceptibility to invasion by Trypanosoma cruzi metacyclic forms and resistance to tissue culture trypomastigotes. Cellular Microbiology, v. 18, n. 5, p. 748-760, MAY 2016. (11/51475-3)

FERREIRA RODRIGUES, JOAO PAULO; TAKAHASHI SANT'ANA, GUILHERME HIDEKI; JULIANO, MARIA APARECIDA; YOSHIDA, NOBUKO. Inhibition of Host Cell Lysosome Spreading by Trypanosoma cruzi Metacyclic Stage-Specific Surface Molecule gp90 Downregulates Parasite Invasion. Infection and Immunity, v. 85, n. 9, SEP 2017. (11/51475-3)

CLEMENTE, TATIANA MORDENTE; CORTEZ, CRISTIAN; NOVAES, ANTONIO DA SILVA; YOSHIDA, NOBUKO. Surface Molecules Released by Trypanosoma cruzi Metacyclic Forms Downregulate Host Cell Invasion. PLoS Neglected Tropical Diseases, v. 10, n. 8, AUG 2016. (11/51475-3)

CHIURILLO, MIGUEL A.; MORAES BARROS, ROBERTO R.; SOUZA, RENATA T.; MARINI, MARJORIE M.; ANTONIO, CRISTIANE R.; CORTEZ, DANIELLE R.; CURTO, MARIA A.; LORENZ, HERNAN A.; SCHIJMAN, ALEJANDRO G.; RAMIREZ, JOSE L.; et al. Subtelomeric I-Scel-Mediated Double-Strand Breaks Are Repaired by Homologous Recombination in Trypanosoma cruzi. FRONTIERS IN MICROBIOLOGY, v. 7, DEC 22 2016. (11/51475-3)

CORDERO, ESTEBAN M.; CORTEZ, CRISTIAN; YOSHIDA, NOBUKO; DA SILVEIRA, JOSE FRANCO. Signal peptide recognition in Trypanosoma cruzi GP82 adhesin relies on its localization at protein N-terminus. SCIENTIFIC REPORTS, v. 9, MAY 13 2019. (12/14369-3, 11/51475-3)

BONFIM-MELO, ALEXIS; FERREIRA, EDEN R.; FLORENTINO, PILAR T. V.; MORTARA, RENATO A.. Amastigote Synapse: The Tricks of Trypanosoma cruzi Extracellular Amastigotes. FRONTIERS IN MICROBIOLOGY, v. 9, JUN 27 2018. (12/21335-8, 12/25282-6, 11/03357-1, 11/51475-3)

FERREIRA, EDEN R.; BONFIM-MELO, ALEXIS; CORDERO, ESTEBAN M.; MORTARA, RENATO A.. ERM Proteins Play Distinct Roles in Cell Invasion by Extracellular Amastigotes of Trypanosoma cruzi. FRONTIERS IN MICROBIOLOGY, v. 8, NOV 21 2017. (11/51475-3, 12/25282-6)

MAEDA, FERNANDO YUKIO; CLEMENTE, TATIANA MORDENTE; MACEDO, SILENE; CORTEZ, CRISTIAN; YOSHIDA, NOBUKO. Host cell invasion and oral infection by Trypanosoma cruzi strains of genetic groups TcI and TcIV from chagasic patients. PARASITES & VECTORS, v. 9, APR 1 2016. (11/51475-3)

FERREIRA, BIANCA L.; FERREIRA, EDEN R.; DE BRITO, MARLON V.; SALU, BRUNO R.; OLIVA, MARIA L. V.; MORTARA, RENATO A.; ORIKAZA, CRISTINA M.. BALB/c and C57BL/6 Mice Cytokine Responses to Trypanosoma cruzi Infection Are Independent of Parasite Strain Infectivity. FRONTIERS IN MICROBIOLOGY, v. 9, MAR 26 2018. (14/21338-2, 11/51475-3)