Identification and functional analysis of Trypanosoma cruzi genes that encode proteins of the glycosylphosphatidylinositol biosynthetic pathway
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2013 |
| Outros Autores: | , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/30686 |
Resumo: | Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil. |
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Cardoso, Mariana SantosGiusta, Caroline JunqueiraTrigueiro, Ricardo C.Shams-Eldin, HosamMacedo, Cristiana S.Araújo, Patrícia RosaGomes, Dawidson AssisMartinelli, Patrícia MassaraKimmel, JürgenStahl, PhilippNiehus, SebastianSchwarz, Ralph T.Previato, José OswaldoPreviato, Lucia MendonçaGazzinelli, Ricardo TostesTeixeira, Santuza Maria Ribeiro2018-12-19T10:44:42Z2018-12-19T10:44:42Z2013CARDOSO, Mariana Santos et al. Identification and functional analysis of Trypanosoma cruzi genes that encode proteins of the glycosylphosphatidylinositol biosynthetic pathway. PLOS Neglected Tropical Diseases, v. 7, n. 8, p. 1-17, e2369, Aug. 2013.1935-2735https://www.arca.fiocruz.br/handle/icict/3068610.1371/journal.pntd.0002369engPublic Library of ScienceTrypanosoma cruziDoença de chagasTrypanosoma cruziChagas diseaseIdentification and functional analysis of Trypanosoma cruzi genes that encode proteins of the glycosylphosphatidylinositol biosynthetic pathwayinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade 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.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.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83082https://www.arca.fiocruz.br/bitstream/icict/30686/1/license.txt9193a7c197bc67acd023525e72a03240MD51ORIGINALIdentification and functional analysis of Trypanosoma cruzi genes.pdfIdentification and functional analysis of Trypanosoma cruzi genes.pdfapplication/pdf11603820https://www.arca.fiocruz.br/bitstream/icict/30686/2/Identification%20and%20functional%20analysis%20of%20Trypanosoma%20cruzi%20genes.pdf4b96cdfd9aa2f9fa2d48841dcbf5ae24MD52TEXTIdentification and functional analysis of Trypanosoma cruzi genes.pdf.txtIdentification and functional analysis of Trypanosoma cruzi genes.pdf.txtExtracted 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| dc.title.pt_BR.fl_str_mv |
Identification and functional analysis of Trypanosoma cruzi genes that encode proteins of the glycosylphosphatidylinositol biosynthetic pathway |
| title |
Identification and functional analysis of Trypanosoma cruzi genes that encode proteins of the glycosylphosphatidylinositol biosynthetic pathway |
| spellingShingle |
Identification and functional analysis of Trypanosoma cruzi genes that encode proteins of the glycosylphosphatidylinositol biosynthetic pathway Cardoso, Mariana Santos Trypanosoma cruzi Doença de chagas Trypanosoma cruzi Chagas disease |
| title_short |
Identification and functional analysis of Trypanosoma cruzi genes that encode proteins of the glycosylphosphatidylinositol biosynthetic pathway |
| title_full |
Identification and functional analysis of Trypanosoma cruzi genes that encode proteins of the glycosylphosphatidylinositol biosynthetic pathway |
| title_fullStr |
Identification and functional analysis of Trypanosoma cruzi genes that encode proteins of the glycosylphosphatidylinositol biosynthetic pathway |
| title_full_unstemmed |
Identification and functional analysis of Trypanosoma cruzi genes that encode proteins of the glycosylphosphatidylinositol biosynthetic pathway |
| title_sort |
Identification and functional analysis of Trypanosoma cruzi genes that encode proteins of the glycosylphosphatidylinositol biosynthetic pathway |
| author |
Cardoso, Mariana Santos |
| author_facet |
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 |
| author_role |
author |
| author2 |
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 |
| author2_role |
author author author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
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 |
| dc.subject.other.pt_BR.fl_str_mv |
Trypanosoma cruzi Doença de chagas |
| topic |
Trypanosoma cruzi Doença de chagas Trypanosoma cruzi Chagas disease |
| dc.subject.en.pt_BR.fl_str_mv |
Trypanosoma cruzi Chagas disease |
| description |
Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil. |
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2013 |
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2013 |
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2018-12-19T10:44:42Z |
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2018-12-19T10:44:42Z |
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info:eu-repo/semantics/article |
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CARDOSO, Mariana Santos et al. Identification and functional analysis of Trypanosoma cruzi genes that encode proteins of the glycosylphosphatidylinositol biosynthetic pathway. PLOS Neglected Tropical Diseases, v. 7, n. 8, p. 1-17, e2369, Aug. 2013. |
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https://www.arca.fiocruz.br/handle/icict/30686 |
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1935-2735 |
| dc.identifier.doi.none.fl_str_mv |
10.1371/journal.pntd.0002369 |
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CARDOSO, Mariana Santos et al. Identification and functional analysis of Trypanosoma cruzi genes that encode proteins of the glycosylphosphatidylinositol biosynthetic pathway. PLOS Neglected Tropical Diseases, v. 7, n. 8, p. 1-17, e2369, Aug. 2013. 1935-2735 10.1371/journal.pntd.0002369 |
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