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Old Yellow Enzyme from Trypanosoma cruzi Exhibits In Vivo Prostaglandin F(2)α Synthase Activity and Has a Key Role in Parasite Infection and Drug Susceptibility

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...

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Autores principales: Díaz-Viraqué, Florencia, Chiribao, María Laura, Trochine, Andrea, González-Herrera, Fabiola, Castillo, Christian, Liempi, Ana, Kemmerling, Ulrike, Maya, Juan Diego, Robello, Carlos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845897/
https://www.ncbi.nlm.nih.gov/pubmed/29563916
http://dx.doi.org/10.3389/fimmu.2018.00456
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author Díaz-Viraqué, Florencia
Chiribao, María Laura
Trochine, Andrea
González-Herrera, Fabiola
Castillo, Christian
Liempi, Ana
Kemmerling, Ulrike
Maya, Juan Diego
Robello, Carlos
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_sort Díaz-Viraqué, Florencia
collection PubMed
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 F(2)α 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 F(2α) 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 PGF(2)α 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.
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spelling pubmed-58458972018-03-21 Old Yellow Enzyme from Trypanosoma cruzi Exhibits In Vivo Prostaglandin F(2)α Synthase Activity and Has a Key Role in Parasite Infection and Drug Susceptibility Díaz-Viraqué, Florencia Chiribao, María Laura Trochine, Andrea González-Herrera, Fabiola Castillo, Christian Liempi, Ana Kemmerling, Ulrike Maya, Juan Diego Robello, Carlos Front Immunol Immunology 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 F(2)α 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 F(2α) 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 PGF(2)α 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. Frontiers Media S.A. 2018-03-07 /pmc/articles/PMC5845897/ /pubmed/29563916 http://dx.doi.org/10.3389/fimmu.2018.00456 Text en Copyright © 2018 Díaz-Viraqué, Chiribao, Trochine, González-Herrera, Castillo, Liempi, Kemmerling, Maya and Robello. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Díaz-Viraqué, Florencia
Chiribao, María Laura
Trochine, Andrea
González-Herrera, Fabiola
Castillo, Christian
Liempi, Ana
Kemmerling, Ulrike
Maya, Juan Diego
Robello, Carlos
Old Yellow Enzyme from Trypanosoma cruzi Exhibits In Vivo Prostaglandin F(2)α Synthase Activity and Has a Key Role in Parasite Infection and Drug Susceptibility
title Old Yellow Enzyme from Trypanosoma cruzi Exhibits In Vivo Prostaglandin F(2)α 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 F(2)α 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 F(2)α 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 F(2)α Synthase Activity and Has a Key Role in Parasite Infection and Drug Susceptibility
title_short Old Yellow Enzyme from Trypanosoma cruzi Exhibits In Vivo Prostaglandin F(2)α 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 f(2)α synthase activity and has a key role in parasite infection and drug susceptibility
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845897/
https://www.ncbi.nlm.nih.gov/pubmed/29563916
http://dx.doi.org/10.3389/fimmu.2018.00456
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