Dataset Information

Gene expression to mitochondrial metabolism: Variability among cultured Trypanosoma cruzi strains.

ABSTRACT: The insect-transmitted protozoan parasite Trypanosoma cruzi experiences changes in nutrient availability and rate of flux through different metabolic pathways across its life cycle. The species encompasses much genetic diversity of both the nuclear and mitochondrial genomes among isolated strains. The genetic or expression variation of both genomes are likely to impact metabolic responses to environmental stimuli, and even steady state metabolic function, among strains. To begin formal characterization these differences, we compared aspects of metabolism between genetically similar strains CL Brener and Tulahuen with less similar Esmeraldo and Sylvio X10 strains in a culture environment. Epimastigotes of all strains took up glucose at similar rates. However, the degree of medium acidification that could be observed when glucose was absent from the medium varied by strain, indicating potential differences in excreted metabolic byproducts. Our main focus was differences related to electron transport chain function. We observed differences in ATP-coupled respiration and maximal respiratory capacity, mitochondrial membrane potential, and mitochondrial morphology between strains, despite the fact that abundances of two nuclear-encoded proteins of the electron transport chain are similar between strains. RNA sequencing reveals strain-specific differences in abundances of mRNAs encoding proteins of the respiratory chain but also other metabolic processes. From these differences in metabolism and mitochondrial phenotypes we have generated tentative models for the differential metabolic fluxes or differences in gene expression that may underlie these results.

SUBMITTER: Kalem MC

PROVIDER: S-EPMC5976161 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Gene expression to mitochondrial metabolism: Variability among cultured Trypanosoma cruzi strains.

Kalem Murat C MC Gerasimov Evgeny S ES Vu Pamela K PK Zimmer Sara L SL

PloS one 20180530 5

The insect-transmitted protozoan parasite Trypanosoma cruzi experiences changes in nutrient availability and rate of flux through different metabolic pathways across its life cycle. The species encompasses much genetic diversity of both the nuclear and mitochondrial genomes among isolated strains. The genetic or expression variation of both genomes are likely to impact metabolic responses to environmental stimuli, and even steady state metabolic function, among strains. To begin formal character ...[more]

PMID: 29847594

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Project description:Trypanosoma cruzi parasites causing Chagas disease are passed between mammals by the triatomine bug vector. Within the insect, T. cruzi epimastigote-stage cells replicate and progress through the increasingly nutrient-restricted digestive tract, differentiating into infectious, nonreplicative metacyclic trypomastigotes. Thus, we evaluated how nutrient perturbations or metacyclogenesis affects mitochondrial gene expression in different insect life cycle stages. We compared mitochondrial RNA abundances in cultures containing fed, replicating epimastigotes, differentiating cultures containing both starved epimastigotes and metacyclic trypomastigotes and epimastigote starvation cultures. We observed increases in mitochondrial rRNAs and some mRNAs in differentiating cultures. These increases predominated only for the edited CYb mRNA in cultures enriched for metacyclic trypomastigotes. For the other transcripts, abundance increases were linked to starvation and were strongest in culture fractions with a high population of starved epimastigotes. We show that loss of both glucose and amino acids results in rapid increases in RNA abundances that are quickly reduced when these nutrients are returned. Furthermore, the individual RNAs exhibit distinct temporal abundance patterns, suggestive of multiple mechanisms regulating individual transcript abundance. Finally, increases in mitochondrial respiratory complex subunit mRNA abundances were not matched by increases in abundances of nucleus-encoded subunit mRNAs, nor were there statistically significant increases in protein levels of three nucleus-encoded subunits tested. These results show that, similarly to that in T. brucei, the mitochondrial genome in T. cruzi has the potential to alter gene expression in response to environmental or developmental stimuli but for an as-yet-unknown purpose. IMPORTANCE 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.

Dataset Information

Gene expression to mitochondrial metabolism: Variability among cultured Trypanosoma cruzi strains.

Publications

Gene expression to mitochondrial metabolism: Variability among cultured Trypanosoma cruzi strains.

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