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

CHIRIBAO ML; CASTILLO C; MAYA JD; DIAZ-VIRAQUÉ F; GONZALEZ F; KEMMERLING U; TROCHINE A; LIEMPI A; ROBELLO C

Frontiers in Immunology

Frontiers

Lugar: Lausanne; Año: 2018 vol. 9 p. 456 - 469

The discovery that trypanosomatids, unicellular organisms of the order Kinetoplastida, are capable of synthesizing prostaglandinsraised questions about the role of these molecules during parasitic infections. Multiple studies indicate that prostaglandins could berelated to the infection processes and pathogenesis in trypanosomatids. This work aimed to unveil the role of the prostaglandinF2α synthase TcOYE in the establishment of Trypanosoma cruzi infection, the causative agent of Chagas disease. This chronicdiseases affects several million people in Latin America causing high morbidity and mortality. Here we propose a prokaryoticevolutionary origin for TcOYE, and then we used in vitro and in vivo experiments to show that T. cruzi prostaglandin F2α synthasehas an important role modulating the infection process. TcOYE overexpressing parasites were less able to complete the infectivecycle in cell culture infections and increased cardiac tissue parasitic load in infected mice. Additionally, parasites overexpressingthe enzyme increased PGF2α synthesis from arachidonic acid. Finally, an increase in Benznidazole and Nifurtimox susceptibility inTcOYE overexpressing parasites showed its participation in activating the currently anti-chagasic drugs, which added to itsobserved ability to confer resistance to hydrogen peroxide, highlights the relevance of this enzyme in multiple events includinghost-parasite interaction.