Mitochondrial Gene Expression Is Responsive to Starvation Stress and Developmental Transition in Trypanosoma cruzi

Abstract

Chagas disease is caused by insect-transmitted Trypanosoma cruzi. Halting T. cruzi’s life cycle in one of its various human and insect life stages would effectively stop the parasite’s infection cycle. T. cruzi is exposed to a variety of environmental conditions in its different life stages, and gene expression must be remodeled to survive these changes. In this work, we look at the impact that one of these changes, nutrient depletion, has on the expression of the 20 gene products encoded in the mitochondrial genome that is neglected by whole-genome studies. We show increases in mitochondrial RNA abundances in starved insect-stage cells, under two conditions in which transition to the infectious stage occurs or does not. This report is the first to show that T. cruzi mitochondrial gene expression is sensitive to environmental perturbations, consistent with mitochondrial gene expression regulatory pathways being potential antiparasitic targets.

A link between mitochondrial gene expression and life stage morphologies inTrypanosoma cruzi

“…Our previous 109 work is the impetuous for these experiments, in which we showed that culture-derived 110 trypomastigotes exhibit higher levels of many mitochondrial RNAs relative to log-stage 111 epimastigotes. However, mRNA abundance is actually highest in the starved epimastigotes 112 rather than in the trypomastigotes of a mixed culture (Shaw et al, 2016). Therefore, we 113 wondered how transient the changes in gene expression upon starvation actually were.…”

“…Theoretically these conditions 229 could reduce rather than increase the need for these RNAs. This is particularly true as most 230 mitochondrial mRNAs encode ETC subunits, and two nuclear-encoded ETC subunits were not 231 found to increase in abundance during starvation ( (Shaw et al, 2016); antibodies cannot be 232 generated to subunits encoded in the mitochondrial genome). To explore this further we asked 233 whether the rRNAs that were increased in starved epimastigotes were incorporated into 234 ribosomes or instead accumulated as non-associated RNAs.…”

“…In a 76 previous study, we found that some of the mitochondrial RNAs that do not require editing in T. 77 cruzi are increased in abundance upon starvation, a fate that is most likely attributable to an 78 increase in stability. However, an even greater increase in abundance was seen specifically for 79 the edited form of mRNAs that require editing, while pre-edited mRNA levels remained largely 80 constant (Shaw et al, 2016). Therefore, some aspect of the editing process is particularly 81 responsive to the starvation signal.…”

Development of a Motion-Based Cell-Counting System for Trypanosoma Parasite Using a Pattern Recognition Approach

“…The infectious stage of T. cruzi (trypomastigote) was obtained by in vitro differentiation of epimastigotes in RPMI medium [5], followed by infection to the host 3T3-Swiss Albino fibroblast cells. The parasitehost co-culture was maintained in DMEM supplemented with 10 FBS at 37C under 5 CO 2 .…”

Benznidazole induces in vitro anaerobic metabolism in Trypanosoma cruzi epimastigotes

“…the metacyclogenesis have been described such as morphology, infectivity and gene expression [10][11][12], the differences in the energetic metabolism throughout the culture growth have not yet been explored. Shah-Simpson et al [13] described the glucose metabolism in epimastigotes, metacyclic trypomastigotes and amastigotes determining the differences in excretion of pyruvate, acetate and alanine.…”