Old Yellow Enzyme from Trypanosoma cruzi exhibits in vivo Prostaglandin F2α synthase activity and has a key role in parasite infection and drug susceptibility

Autores
Díaz-Viraqué, Florencia; Chiribao, María Laura; Trochine, Andrea; González Herrera, Fabiola; Castillo, Christian; Liempi, Ana; Kemmerling, Ulrike; Maya, Juan Diego; Robello, Carlos
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The discovery that trypanosomatids, unicellular organisms of the order Kinetoplastida, are capable of synthesizing prostaglandins raised questions about the role of these molecules during parasitic infections. Multiple studies indicate that prostaglandins could be related to the infection processes and pathogenesis in trypanosomatids. This work aimed to unveil the role of the prostaglandin F2α synthase TcOYE in the establishment of Trypanosoma cruzi infection, the causative agent of Chagas disease. This chronic disease affects several million people in Latin America causing high morbidity and mortality. Here, we propose a prokaryotic evolutionary origin for TcOYE, and then we used in vitro and in vivo experiments to show that T. cruzi prostaglandin F2α synthase plays an important role in modulating the infection process. TcOYE overexpressing parasites were less able to complete the infective cycle in cell culture infections and increased cardiac tissue parasitic load in infected mice. Additionally, parasites overexpressing the enzyme increased PGF2α synthesis from arachidonic acid. Finally, an increase in benznidazole and nifurtimox susceptibility in TcOYE overexpressing parasites showed its participation in activating the currently anti-chagasic drugs, which added to its observed ability to confer resistance to hydrogen peroxide, highlights the relevance of this enzyme in multiple events including host-parasite interaction.
Fil: Díaz-Viraqué, Florencia. Instituto Pasteur de Montevideo; Uruguay
Fil: Chiribao, María Laura. Instituto Pasteur de Montevideo; Uruguay. Universidad de la República; Uruguay
Fil: Trochine, Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto Andino Patagónico de Tecnologías Biológicas y Geoambientales. Universidad Nacional del Comahue. Instituto Andino Patagónico de Tecnologías Biológicas y Geoambientales.; Argentina. Instituto Pasteur de Montevideo; Uruguay
Fil: González Herrera, Fabiola. Universidad de Chile; Chile
Fil: Castillo, Christian. Universidad de Chile; Chile
Fil: Liempi, Ana. Universidad de Chile; Chile
Fil: Kemmerling, Ulrike. Universidad de Chile; Chile
Fil: Maya, Juan Diego. Universidad de Chile; Chile
Fil: Robello, Carlos. Instituto Pasteur de Montevideo; Uruguay. Universidad de la República; Uruguay
Materia
BENZNIDAZOL AND NIFURTIMOX ACTIVATION
DIFFERENTIALLY EXPRESSED GENE
OLD YELLOW ENZYME
PROSTAGLANDIN F2A SYNTHASE
TRYPANOSOMA CRUZI
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/89314
Acceder
id CONICETDig_78468ea6be581fed6099a5908acc83e9
oai_identifier_str oai:ri.conicet.gov.ar:11336/89314
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Old Yellow Enzyme from Trypanosoma cruzi exhibits in vivo Prostaglandin F2α synthase activity and has a key role in parasite infection and drug susceptibilityDíaz-Viraqué, FlorenciaChiribao, María LauraTrochine, AndreaGonzález Herrera, FabiolaCastillo, ChristianLiempi, AnaKemmerling, UlrikeMaya, Juan DiegoRobello, CarlosBENZNIDAZOL AND NIFURTIMOX ACTIVATIONDIFFERENTIALLY EXPRESSED GENEOLD YELLOW ENZYMEPROSTAGLANDIN F2A SYNTHASETRYPANOSOMA CRUZIhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The discovery that trypanosomatids, unicellular organisms of the order Kinetoplastida, are capable of synthesizing prostaglandins raised questions about the role of these molecules during parasitic infections. Multiple studies indicate that prostaglandins could be related to the infection processes and pathogenesis in trypanosomatids. This work aimed to unveil the role of the prostaglandin F2α synthase TcOYE in the establishment of Trypanosoma cruzi infection, the causative agent of Chagas disease. This chronic disease affects several million people in Latin America causing high morbidity and mortality. Here, we propose a prokaryotic evolutionary origin for TcOYE, and then we used in vitro and in vivo experiments to show that T. cruzi prostaglandin F2α synthase plays an important role in modulating the infection process. TcOYE overexpressing parasites were less able to complete the infective cycle in cell culture infections and increased cardiac tissue parasitic load in infected mice. Additionally, parasites overexpressing the enzyme increased PGF2α synthesis from arachidonic acid. Finally, an increase in benznidazole and nifurtimox susceptibility in TcOYE overexpressing parasites showed its participation in activating the currently anti-chagasic drugs, which added to its observed ability to confer resistance to hydrogen peroxide, highlights the relevance of this enzyme in multiple events including host-parasite interaction.Fil: Díaz-Viraqué, Florencia. Instituto Pasteur de Montevideo; UruguayFil: Chiribao, María Laura. Instituto Pasteur de Montevideo; Uruguay. Universidad de la República; UruguayFil: Trochine, Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto Andino Patagónico de Tecnologías Biológicas y Geoambientales. Universidad Nacional del Comahue. Instituto Andino Patagónico de Tecnologías Biológicas y Geoambientales.; Argentina. Instituto Pasteur de Montevideo; UruguayFil: González Herrera, Fabiola. Universidad de Chile; ChileFil: Castillo, Christian. Universidad de Chile; ChileFil: Liempi, Ana. Universidad de Chile; ChileFil: Kemmerling, Ulrike. Universidad de Chile; ChileFil: Maya, Juan Diego. Universidad de Chile; ChileFil: Robello, Carlos. Instituto Pasteur de Montevideo; Uruguay. Universidad de la República; UruguayFrontiers Media SA2018-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/89314Díaz-Viraqué, Florencia; Chiribao, María Laura; Trochine, Andrea; González Herrera, Fabiola; Castillo, Christian; et al.; Old Yellow Enzyme from Trypanosoma cruzi exhibits in vivo Prostaglandin F2α synthase activity and has a key role in parasite infection and drug susceptibility; Frontiers Media SA; Frontiers in Immunology; 9; 3-2018; 456-4691664-3224CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2018.00456info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fimmu.2018.00456/fullinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:02:05Zoai:ri.conicet.gov.ar:11336/89314instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:02:05.534CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Old Yellow Enzyme from Trypanosoma cruzi exhibits in vivo Prostaglandin F2α synthase activity and has a key role in parasite infection and drug susceptibility
title Old Yellow Enzyme from Trypanosoma cruzi exhibits in vivo Prostaglandin F2α synthase activity and has a key role in parasite infection and drug susceptibility
spellingShingle Old Yellow Enzyme from Trypanosoma cruzi exhibits in vivo Prostaglandin F2α synthase activity and has a key role in parasite infection and drug susceptibility
Díaz-Viraqué, Florencia
BENZNIDAZOL AND NIFURTIMOX ACTIVATION
DIFFERENTIALLY EXPRESSED GENE
OLD YELLOW ENZYME
PROSTAGLANDIN F2A SYNTHASE
TRYPANOSOMA CRUZI
title_short Old Yellow Enzyme from Trypanosoma cruzi exhibits in vivo Prostaglandin F2α synthase activity and has a key role in parasite infection and drug susceptibility
title_full Old Yellow Enzyme from Trypanosoma cruzi exhibits in vivo Prostaglandin F2α synthase activity and has a key role in parasite infection and drug susceptibility
title_fullStr Old Yellow Enzyme from Trypanosoma cruzi exhibits in vivo Prostaglandin F2α synthase activity and has a key role in parasite infection and drug susceptibility
title_full_unstemmed Old Yellow Enzyme from Trypanosoma cruzi exhibits in vivo Prostaglandin F2α synthase activity and has a key role in parasite infection and drug susceptibility
title_sort Old Yellow Enzyme from Trypanosoma cruzi exhibits in vivo Prostaglandin F2α synthase activity and has a key role in parasite infection and drug susceptibility
dc.creator.none.fl_str_mv Díaz-Viraqué, Florencia
Chiribao, María Laura
Trochine, Andrea
González Herrera, Fabiola
Castillo, Christian
Liempi, Ana
Kemmerling, Ulrike
Maya, Juan Diego
Robello, Carlos
author Díaz-Viraqué, Florencia
author_facet Díaz-Viraqué, Florencia
Chiribao, María Laura
Trochine, Andrea
González Herrera, Fabiola
Castillo, Christian
Liempi, Ana
Kemmerling, Ulrike
Maya, Juan Diego
Robello, Carlos
author_role author
author2 Chiribao, María Laura
Trochine, Andrea
González Herrera, Fabiola
Castillo, Christian
Liempi, Ana
Kemmerling, Ulrike
Maya, Juan Diego
Robello, Carlos
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv BENZNIDAZOL AND NIFURTIMOX ACTIVATION
DIFFERENTIALLY EXPRESSED GENE
OLD YELLOW ENZYME
PROSTAGLANDIN F2A SYNTHASE
TRYPANOSOMA CRUZI
topic BENZNIDAZOL AND NIFURTIMOX ACTIVATION
DIFFERENTIALLY EXPRESSED GENE
OLD YELLOW ENZYME
PROSTAGLANDIN F2A SYNTHASE
TRYPANOSOMA CRUZI
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The discovery that trypanosomatids, unicellular organisms of the order Kinetoplastida, are capable of synthesizing prostaglandins raised questions about the role of these molecules during parasitic infections. Multiple studies indicate that prostaglandins could be related to the infection processes and pathogenesis in trypanosomatids. This work aimed to unveil the role of the prostaglandin F2α synthase TcOYE in the establishment of Trypanosoma cruzi infection, the causative agent of Chagas disease. This chronic disease affects several million people in Latin America causing high morbidity and mortality. Here, we propose a prokaryotic evolutionary origin for TcOYE, and then we used in vitro and in vivo experiments to show that T. cruzi prostaglandin F2α synthase plays an important role in modulating the infection process. TcOYE overexpressing parasites were less able to complete the infective cycle in cell culture infections and increased cardiac tissue parasitic load in infected mice. Additionally, parasites overexpressing the enzyme increased PGF2α synthesis from arachidonic acid. Finally, an increase in benznidazole and nifurtimox susceptibility in TcOYE overexpressing parasites showed its participation in activating the currently anti-chagasic drugs, which added to its observed ability to confer resistance to hydrogen peroxide, highlights the relevance of this enzyme in multiple events including host-parasite interaction.
Fil: Díaz-Viraqué, Florencia. Instituto Pasteur de Montevideo; Uruguay
Fil: Chiribao, María Laura. Instituto Pasteur de Montevideo; Uruguay. Universidad de la República; Uruguay
Fil: Trochine, Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto Andino Patagónico de Tecnologías Biológicas y Geoambientales. Universidad Nacional del Comahue. Instituto Andino Patagónico de Tecnologías Biológicas y Geoambientales.; Argentina. Instituto Pasteur de Montevideo; Uruguay
Fil: González Herrera, Fabiola. Universidad de Chile; Chile
Fil: Castillo, Christian. Universidad de Chile; Chile
Fil: Liempi, Ana. Universidad de Chile; Chile
Fil: Kemmerling, Ulrike. Universidad de Chile; Chile
Fil: Maya, Juan Diego. Universidad de Chile; Chile
Fil: Robello, Carlos. Instituto Pasteur de Montevideo; Uruguay. Universidad de la República; Uruguay
description The discovery that trypanosomatids, unicellular organisms of the order Kinetoplastida, are capable of synthesizing prostaglandins raised questions about the role of these molecules during parasitic infections. Multiple studies indicate that prostaglandins could be related to the infection processes and pathogenesis in trypanosomatids. This work aimed to unveil the role of the prostaglandin F2α synthase TcOYE in the establishment of Trypanosoma cruzi infection, the causative agent of Chagas disease. This chronic disease affects several million people in Latin America causing high morbidity and mortality. Here, we propose a prokaryotic evolutionary origin for TcOYE, and then we used in vitro and in vivo experiments to show that T. cruzi prostaglandin F2α synthase plays an important role in modulating the infection process. TcOYE overexpressing parasites were less able to complete the infective cycle in cell culture infections and increased cardiac tissue parasitic load in infected mice. Additionally, parasites overexpressing the enzyme increased PGF2α synthesis from arachidonic acid. Finally, an increase in benznidazole and nifurtimox susceptibility in TcOYE overexpressing parasites showed its participation in activating the currently anti-chagasic drugs, which added to its observed ability to confer resistance to hydrogen peroxide, highlights the relevance of this enzyme in multiple events including host-parasite interaction.
publishDate 2018
dc.date.none.fl_str_mv 2018-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/89314
Díaz-Viraqué, Florencia; Chiribao, María Laura; Trochine, Andrea; González Herrera, Fabiola; Castillo, Christian; et al.; Old Yellow Enzyme from Trypanosoma cruzi exhibits in vivo Prostaglandin F2α synthase activity and has a key role in parasite infection and drug susceptibility; Frontiers Media SA; Frontiers in Immunology; 9; 3-2018; 456-469
1664-3224
CONICET Digital
CONICET
url http://hdl.handle.net/11336/89314
identifier_str_mv Díaz-Viraqué, Florencia; Chiribao, María Laura; Trochine, Andrea; González Herrera, Fabiola; Castillo, Christian; et al.; Old Yellow Enzyme from Trypanosoma cruzi exhibits in vivo Prostaglandin F2α synthase activity and has a key role in parasite infection and drug susceptibility; Frontiers Media SA; Frontiers in Immunology; 9; 3-2018; 456-469
1664-3224
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2018.00456
info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fimmu.2018.00456/full
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media SA
publisher.none.fl_str_mv Frontiers Media SA
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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