Metabolic interplay and flexibility in the intracellular Trypanosoma cruzi‐host cell interaction

Abstract

The mammalian stages of the protozoan parasite and causative agent of Chagas disease, Trypanosoma cruzi, exhibit a wide host species range and extensive within‐host tissue distribution. These features, coupled with the ability of T. cruzi to persist for the lifetime of its mammalian host, suggest an inherent capacity of the parasite to respond flexibly to local changing environments. To explore this potential, the population‐level response of intracellular T. cruzi amastigotes to various metabolic perturbations was examined by measuring proliferation rates and cell cycle dynamics. Intracellular amastigotes responded to transient perturbations with a rapid and reversible suppression of proliferation rates, that in most instances, was accompanied by the reversible accumulation of parasites in the G1 phase of the cell cycle. Further, our examination of the impact of the immediate metabolic environment on the susceptibility of intracellular T. cruzi amastigotes to trypanocidal drugs lead to the finding that a single change in the composition of the cell culture medium, restriction of glutamine, protects intracellular T. cruzi amastigotes from the lethal effects of the ergosterol biosynthesis inhibitors, ketoconazole and posaconazole. The implications of this finding will be discussed along with the results of ongoing molecular genetic experiments designed to elucidate the metabolic basis of this finding.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.