10.3389/fimmu.2018.00456.s004 Florencia Díaz-Viraqué Florencia Díaz-Viraqué María Laura Chiribao María Laura Chiribao Andrea Trochine Andrea Trochine Fabiola González-Herrera Fabiola González-Herrera Christian Castillo Christian Castillo Ana Liempi Ana Liempi Ulrike Kemmerling Ulrike Kemmerling Juan Diego Maya Juan Diego Maya Carlos Robello Carlos Robello image_4.tif Frontiers 2018 Trypanosoma cruzi prostaglandin F2α synthase Old Yellow Enzyme differentially expressed gene benznidazol and nifurtimox activation 2018-03-07 04:28:53 Figure https://frontiersin.figshare.com/articles/figure/image_4_tif/5954809 <p>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<sub>2</sub>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<sub>2α</sub> 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<sub>2</sub>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.</p>