Disruption of multiple copies of the Prostaglandin F2alpha synthase gene affects oxidative stress response and infectivity in Trypanosoma cruzi

Santi, Ana Maria Murta; Ribeiro, Juliana Martins; Reis-Cunha, João Luís; Burle-Caldas, Gabriela de Assis; Santos, Isabella Fernandes Martins; Silva, Paula Alves; Resende, Daniela de Melo; Bartholomeu, Daniella Castanheira; Teixeira, Santuza Maria Ribeiro; Murta, Silvane Maria Fonseca

Disruption of multiple copies of the Prostaglandin F2alpha synthase gene affects oxidative stress response and infectivity in Trypanosoma cruzi

Detalhes bibliográficos
Autor(a) principal:	Santi, Ana Maria Murta
Data de Publicação:	2022
Outros Autores:	Ribeiro, Juliana Martins, Reis-Cunha, João Luís, Burle-Caldas, Gabriela de Assis, Santos, Isabella Fernandes Martins, Silva, Paula Alves, Resende, Daniela de Melo, Bartholomeu, Daniella Castanheira, Teixeira, Santuza Maria Ribeiro, Murta, Silvane Maria Fonseca
Tipo de documento:	Artigo
Idioma:	eng
Título da fonte:	Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo:	https://www.arca.fiocruz.br/handle/icict/56914
Resumo:	Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Genômica Funcional de Parasitos. Belo Horizonte, MG, Brazil.

Metadados do item

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spelling	Santi, Ana Maria MurtaRibeiro, Juliana MartinsReis-Cunha, João LuísBurle-Caldas, Gabriela de AssisSantos, Isabella Fernandes MartinsSilva, Paula AlvesResende, Daniela de MeloBartholomeu, Daniella CastanheiraTeixeira, Santuza Maria RibeiroMurta, Silvane Maria Fonseca2023-02-07T13:22:14Z2023-02-07T13:22:14Z2022SANTI, Ana Maria Murta et al. Disruption of multiple copies of the Prostaglandin F2alpha synthase gene affects oxidative stress response and infectivity in Trypanosoma cruzi. PLoS Negl Trop Dis., v. 16, n. 10, e0010845, 2022. doi: 10.1371/journal.pntd.0010845.1935-2735https://www.arca.fiocruz.br/handle/icict/56914engPublic Library of ScienceDisruption of multiple copies of the Prostaglandin F2alpha synthase gene affects oxidative stress response and infectivity in Trypanosoma cruziinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto René Rachou. Grupo Genômica Funcional de Parasitos. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Genômica Funcional de Parasitos. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Parasitologia. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Escola de Veterinária. Departamento de Medicina Veterinária Preventiva. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Genômica Funcional de Parasitos. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Genômica Funcional de Parasitos. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Genômica Funcional de Parasitos. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Parasitologia. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Genômica Funcional de Parasitos. Belo Horizonte, MG, Brazil.Chagas disease, caused by the protozoan Trypanosoma cruzi, is a serious chronic parasitic disease, currently treated with Nifurtimox (NFX) and Benznidazole (BZ). In addition to high toxicity, these drugs have low healing efficacy, especially in the chronic phase of the disease. The existence of drug-resistant T. cruzi strains and the occurrence of cross-resistance between BZ and NFX have also been described. In this context, it is urgent to study the metabolism of these drugs in T. cruzi, to better understand the mechanisms of resistance. Prostaglandin F2α synthase (PGFS) is an enzyme that has been correlated with parasite resistance to BZ, but the mechanism by which resistance occurs is still unclear. Our results show that the genome of the CL Brener clone of T. cruzi, contains five PGFS sequences and three potential pseudogenes. Using CRISPR/Cas9 we generated knockout cell lines in which all PGFS sequences were disrupted, as shown by PCR and western blotting analyses. The PGFS deletion did not alter the growth of the parasites or their susceptibility to BZ and NFX when compared to wild-type (WT) parasites. Interestingly, NTR-1 transcripts were shown to be upregulated in ΔPGFS mutants. Furthermore, the ΔPGFS parasites were 1.6 to 1.7-fold less tolerant to oxidative stress generated by menadione, presented lower levels of lipid bodies than the control parasites during the stationary phase, and were less infective than control parasites.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/56914/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALDisruption of multiple copies of the Prostaglandin.pdfDisruption of multiple copies of the Prostaglandin.pdfapplication/pdf2090982https://www.arca.fiocruz.br/bitstream/icict/56914/2/Disruption%20of%20multiple%20copies%20of%20the%20Prostaglandin.pdf46ff4f0b17dedb79b9b8debc3714ac69MD52icict/569142023-02-07 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dc.title.en_US.fl_str_mv	Disruption of multiple copies of the Prostaglandin F2alpha synthase gene affects oxidative stress response and infectivity in Trypanosoma cruzi
title	Disruption of multiple copies of the Prostaglandin F2alpha synthase gene affects oxidative stress response and infectivity in Trypanosoma cruzi
spellingShingle	Disruption of multiple copies of the Prostaglandin F2alpha synthase gene affects oxidative stress response and infectivity in Trypanosoma cruzi Santi, Ana Maria Murta
title_short	Disruption of multiple copies of the Prostaglandin F2alpha synthase gene affects oxidative stress response and infectivity in Trypanosoma cruzi
title_full	Disruption of multiple copies of the Prostaglandin F2alpha synthase gene affects oxidative stress response and infectivity in Trypanosoma cruzi
title_fullStr	Disruption of multiple copies of the Prostaglandin F2alpha synthase gene affects oxidative stress response and infectivity in Trypanosoma cruzi
title_full_unstemmed	Disruption of multiple copies of the Prostaglandin F2alpha synthase gene affects oxidative stress response and infectivity in Trypanosoma cruzi
title_sort	Disruption of multiple copies of the Prostaglandin F2alpha synthase gene affects oxidative stress response and infectivity in Trypanosoma cruzi
author	Santi, Ana Maria Murta
author_facet	Santi, Ana Maria Murta Ribeiro, Juliana Martins Reis-Cunha, João Luís Burle-Caldas, Gabriela de Assis Santos, Isabella Fernandes Martins Silva, Paula Alves Resende, Daniela de Melo Bartholomeu, Daniella Castanheira Teixeira, Santuza Maria Ribeiro Murta, Silvane Maria Fonseca
author_role	author
author2	Ribeiro, Juliana Martins Reis-Cunha, João Luís Burle-Caldas, Gabriela de Assis Santos, Isabella Fernandes Martins Silva, Paula Alves Resende, Daniela de Melo Bartholomeu, Daniella Castanheira Teixeira, Santuza Maria Ribeiro Murta, Silvane Maria Fonseca
author2_role	author author author author author author author author author
dc.contributor.author.fl_str_mv	Santi, Ana Maria Murta Ribeiro, Juliana Martins Reis-Cunha, João Luís Burle-Caldas, Gabriela de Assis Santos, Isabella Fernandes Martins Silva, Paula Alves Resende, Daniela de Melo Bartholomeu, Daniella Castanheira Teixeira, Santuza Maria Ribeiro Murta, Silvane Maria Fonseca
description	Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Genômica Funcional de Parasitos. Belo Horizonte, MG, Brazil.
publishDate	2022
dc.date.issued.fl_str_mv	2022
dc.date.accessioned.fl_str_mv	2023-02-07T13:22:14Z
dc.date.available.fl_str_mv	2023-02-07T13:22:14Z
dc.type.status.fl_str_mv	info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv	info:eu-repo/semantics/article
format	article
status_str	publishedVersion
dc.identifier.citation.fl_str_mv	SANTI, Ana Maria Murta et al. Disruption of multiple copies of the Prostaglandin F2alpha synthase gene affects oxidative stress response and infectivity in Trypanosoma cruzi. PLoS Negl Trop Dis., v. 16, n. 10, e0010845, 2022. doi: 10.1371/journal.pntd.0010845.
dc.identifier.uri.fl_str_mv	https://www.arca.fiocruz.br/handle/icict/56914
dc.identifier.issn.en_US.fl_str_mv	1935-2735
identifier_str_mv	SANTI, Ana Maria Murta et al. Disruption of multiple copies of the Prostaglandin F2alpha synthase gene affects oxidative stress response and infectivity in Trypanosoma cruzi. PLoS Negl Trop Dis., v. 16, n. 10, e0010845, 2022. doi: 10.1371/journal.pntd.0010845. 1935-2735
url	https://www.arca.fiocruz.br/handle/icict/56914
dc.language.iso.fl_str_mv	eng
language	eng
dc.rights.driver.fl_str_mv	info:eu-repo/semantics/openAccess
eu_rights_str_mv	openAccess
dc.publisher.none.fl_str_mv	Public Library of Science
publisher.none.fl_str_mv	Public Library of Science
dc.source.none.fl_str_mv	reponame:Repositório Institucional da FIOCRUZ (ARCA) instname:Fundação Oswaldo Cruz (FIOCRUZ) instacron:FIOCRUZ
instname_str	Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str	FIOCRUZ
institution	FIOCRUZ
reponame_str	Repositório Institucional da FIOCRUZ (ARCA)
collection	Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv	https://www.arca.fiocruz.br/bitstream/icict/56914/1/license.txt https://www.arca.fiocruz.br/bitstream/icict/56914/2/Disruption%20of%20multiple%20copies%20of%20the%20Prostaglandin.pdf
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repository.name.fl_str_mv	Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
repository.mail.fl_str_mv	repositorio.arca@fiocruz.br
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Disruption of multiple copies of the Prostaglandin F2alpha synthase gene affects oxidative stress response and infectivity in Trypanosoma cruzi

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