Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/30686
Title: Identification and functional analysis of Trypanosoma cruzi genes that encode proteins of the glycosylphosphatidylinositol biosynthetic pathway
Authors: Cardoso, Mariana Santos
Giusta, Caroline Junqueira
Trigueiro, Ricardo C.
Shams-Eldin, Hosam
Macedo, Cristiana S.
Araújo, Patrícia Rosa
Gomes, Dawidson Assis
Martinelli, Patrícia Massara
Kimmel, Jürgen
Stahl, Philipp
Niehus, Sebastian
Schwarz, Ralph T.
Previato, José Oswaldo
Previato, Lucia Mendonça
Gazzinelli, Ricardo Tostes
Teixeira, Santuza Maria Ribeiro
Affilliation: Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil
Institut für Virologie – AG Parasitologie. Philipps-Universität Marburg. Marburg, Germany
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas. Rio de Janeiro, RJ, 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 Minas Gerais. Departamento de Morfologia. Belo Horizonte, MG, Brazil
Institut für Virologie – AG Parasitologie. Philipps-Universität Marburg. Marburg, Germany
Institut für Virologie – AG Parasitologie. Philipps-Universität Marburg. Marburg, Germany
Institut für Virologie – AG Parasitologie. Philipps-Universität Marburg. Marburg, Germany
Institut für Virologie – AG Parasitologie. Philipps-Universität Marburg. Marburg, Germany
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas. Rio de Janeiro, RJ, Brazil
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas. Rio de Janeiro, RJ, Brazil
Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil/Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil
Abstract: BACKGROUND: Trypanosoma cruzi is a protist parasite that causes Chagas disease. Several proteins that are essential for parasite virulence and involved in host immune responses are anchored to the membrane through glycosylphosphatidylinositol (GPI) molecules. In addition, T. cruzi GPI anchors have immunostimulatory activities, including the ability to stimulate the synthesis of cytokines by innate immune cells. Therefore, T. cruzi genes related to GPI anchor biosynthesis constitute potential new targets for the development of better therapies against Chagas disease. METHODOLOGY/PRINCIPAL FINDINGS: In silico analysis of the T. cruzi genome resulted in the identification of 18 genes encoding proteins of the GPI biosynthetic pathway as well as the inositolphosphorylceramide (IPC) synthase gene. Expression of GFP fusions of some of these proteins in T. cruzi epimastigotes showed that they localize in the endoplasmic reticulum (ER). Expression analyses of two genes indicated that they are constitutively expressed in all stages of the parasite life cycle. T. cruzi genes TcDPM1, TcGPI10 and TcGPI12 complement conditional yeast mutants in GPI biosynthesis. Attempts to generate T. cruzi knockouts for three genes were unsuccessful, suggesting that GPI may be an essential component of the parasite. Regarding TcGPI8, which encodes the catalytic subunit of the transamidase complex, although we were able to generate single allele knockout mutants, attempts to disrupt both alleles failed, resulting instead in parasites that have undergone genomic recombination and maintained at least one active copy of the gene. CONCLUSIONS/SIGNIFICANCE: Analyses of T. cruzi sequences encoding components of the GPI biosynthetic pathway indicated that they are essential genes involved in key aspects of host-parasite interactions. Complementation assays of yeast mutants with these T. cruzi genes resulted in yeast cell lines that can now be employed in high throughput screenings of drugs against this parasite.
Keywords: Trypanosoma cruzi
Chagas disease
keywords: Trypanosoma cruzi
Doença de chagas
Issue Date: 2013
Publisher: Public Library of Science
Citation: CARDOSO, Mariana Santos et al. Identification and functional analysis of Trypanosoma cruzi genes that encode proteins of the glycosylphosphatidylinositol biosynthetic pathway. PLoS Negl Trop Dis., v. 7, n. 8, e2369, 2013.
DOI: 10.1371/journal.pntd.0002369
ISSN: 1935-2735
Copyright: open access
Appears in Collections:MG - IRR - Artigos de Periódicos

Files in This Item:
File Description SizeFormat 
Identification and functional analysis of Trypanosoma cruzi genes.pdf11.33 MBAdobe PDFView/Open



FacebookTwitterDeliciousLinkedInGoogle BookmarksBibTex Format mendeley Endnote DiggMySpace

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.