Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/25171
Title: Comparative transcriptome profiling of virulent and non-virulent Trypanosoma cruzi underlines the role of surface proteins during infection
Authors: Belew, Ashton Trey
Giusta, Caroline Junqueira
Luiz, Gabriela Flavia Rodrigues
Valente, Bruna Mattioly
Oliveira, Antonio Edson Rocha
Polidoro, Rafael Barbosa
Zuccherato, Luciana Werneck
Bartholomeu, Daniella Castanheira
Schenkman, Sergio
Gazzinelli, Ricardo Tostes
Burleigh, Barbara A
El-Sayed, Najib M.
Teixeira, Santuza Maria Ribeiro
Affilliation: University of Maryland. College Park. Department of Cell Biology and Molecular Genetics and Center for Bioinformatics and Computational Biology. Maryland, United States of America
Fundação Oswaldo Cruz. Instituto Rene Rachou. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil
Universidade Federal de São Paulo. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brazil
Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brazil
Universidade Federal de São Paulo. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brazil
Fundação Oswaldo Cruz. Instituto Rene Rachou. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil
Harvard T. H. Chan School of Public Health. Department of Immunology and Infectious Diseases. Boston, Massachusetts, United States of America
University of Maryland. College Park. Department of Cell Biology and Molecular Genetics and Center for Bioinformatics and Computational Biology. Maryland, United States of America
Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil
Abstract: Trypanosoma cruzi, the protozoan that causes Chagas disease, has a complex life cycle involving several morphologically and biochemically distinct stages that establish intricate interactions with various insect and mammalian hosts. It has also a heterogeneous population structure comprising strains with distinct properties such as virulence, sensitivity to drugs, antigenic profile and tissue tropism. We present a comparative transcriptome analysis of two cloned T. cruzi strains that display contrasting virulence phenotypes in animal models of infection: CL Brener is a virulent clone and CL-14 is a clone that is neither infective nor pathogenic in in vivo models of infection. Gene expression analysis of trypomastigotes and intracellular amastigotes harvested at 60 and 96 hours post-infection (hpi) of human fibroblasts revealed large differences that reflect the parasite’s adaptation to distinct environments during the infection of mammalian cells, including changes in energy sources, oxidative stress responses, cell cycle control and cell surface components. While extensive transcriptome remodeling was observed when trypomastigotes of both strains were compared to 60 hpi amastigotes, differences in gene expression were much less pronounced when 96 hpi amastigotes and trypomastigotes of CL Brener were compared. In contrast, the differentiation of the avirulent CL-14 from 96 hpi amastigotes to extracellular trypomastigotes was associated with considerable changes in gene expression, particularly in gene families encoding surface proteins such as trans-sialidases, mucins and the mucin associated surface proteins (MASPs). Thus, our comparative transcriptome analysis indicates that the avirulent phenotype of CL-14 may be due, at least in part, to a reduced or delayed expression of genes encoding surface proteins that are associated with the transition of amastigotes to trypomastigotes, an essential step in the establishment of the infection in the mammalian host. Confirming the role of members of the trans-sialidase family of surface proteins for parasite differentiation, transfected CL-14 constitutively expressing a trans-sialidase gene displayed faster kinetics of trypomastigote release in the supernatant of infected cells compared to wild type CL-14
Keywords: Amastigotes
Trypomastigotes
Gene expression
Parasitic diseases
Trypanosoma cruzi
Cell differentiation
Epimastigotes
Comparative genomic
keywords: Amastigotas
Trypanosoma cruzi
Issue Date: 2017
Publisher: Public Library of Science
Citation: BELEW, Ashton Trey et al. Comparative transcriptome profiling of virulent and non-virulent Trypanosoma cruzi underlines the role of surface proteins during infection. PLoS Pathog., v. 13, n. 12, art. e1006767, 2017.
DOI: 10.1371/journal.ppat.1006767
ISSN: 1553-7366
Copyright: open access
Appears in Collections:MG - IRR - Artigos de Periódicos

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