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

Bibliographic Details
Main Author: Santi, Ana Maria Murta
Publication Date: 2022
Other Authors: 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
Format: Article
Language: eng
Source: Repositório Institucional da FIOCRUZ (ARCA)
Download full: https://www.arca.fiocruz.br/handle/icict/56914
Summary: Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Genômica Funcional de Parasitos. Belo Horizonte, MG, Brazil.
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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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