Biology subjects

Tevere, E.

Publications and source records attributed to Tevere, E..

3 recordsLinked to original sources

bioRxiv2025

Transcriptomic response to different heme sources in Trypanosoma cruzi

Heme is an essential molecule for most organisms, yet some parasites, like Trypanosoma cruzi, the causative agent of Chagas disease, cannot synthesize it. These parasites must acquire heme from their hosts, making this process critical for their survival. In the midgut of the insect vector, T. cruzi epimastigotes are exposed to both hemoglobin (Hb) and free heme resulting from its degradation. Despite the importance of this nutrient, how different heme sources influence parasite gene expression remains poorly understood. Here, we showed that heme restitution either as hemin or Hb to heme-starved parasites induces an early and distinct transcriptional response in T. cruzi epimastigotes. Using RNA sequencing at 4- and 24-hours post-supplementation, we identified gene subsets commonly or uniquely regulated by each heme source, including genes putatively linked to heme acquisition and metabolism. We also presented here the first studies focused on CRAL/TRIO domain-containing protein (TcCRAL/TRIO), a novel heme responsive hemoprotein identified from this study. Our results provide a more detailed picture of T. cruzi biology and highlights heme acquisition as a promising point of vulnerability. These findings may ultimately contribute to the identification of potential molecular targets for the development of new therapeutic strategies against Chagas disease.

biochemistry↗

bioRxiv2023

TcHRG plays a central role in orchestrating heme uptake in Trypanosoma cruzi epimastigotes

Trypanosoma cruzi, a heme auxotrophic parasite, can control intracellular heme content by modulating TcHRG expression when a free heme source is added to axenic culture. Herein, we explore the role of TcHRG protein in regulating the uptake of heme derived from hemoglobin in epimastigotes. It was found that the parasites endogenous TcHRG (protein and mRNA) responds similarly to bound (hemoglobin) and free (hemin) heme. Additionally, the overexpression of TcHRG leads to an increase in intracellular heme content. The localization of TcHRG is also not affected in parasites supplemented with hemoglobin as the sole heme source. Endocytic null epimastigotes do not show a significant difference in growth profile, intracellular heme content and TcHRG protein accumulation compared to WT when feeding with hemoglobin or hemin as a source of heme. These results suggest that the uptake of hemoglobin-derived heme likely occurs through extracellular proteolysis of hemoglobin via the flagellar pocket, and this process is governed by TcHRG. In sum, T. cruzi epimastigotes controls heme homeostasis by modulating TcHRG expression independently of the source of available heme.

biochemistry↗

bioRxiv2020

Trypanosoma cruzi senses intracellular heme levels and regulates heme homeostasis by modulating TcHTE protein expression

Heme is an essential cofactor for many biological processes in aerobic organisms. Unlike most organisms, which can synthesize it de novo through a conserved pathway, the etiological agent of Chagas disease, Trypanosoma cruzi, as well as other trypanosomatids relevant for human health, are heme auxotrophs; thereby they must import it from the hosts. TcHTE protein is involved in T. cruzi heme transport, although its specific role remains elusive. In the present work we studied endogenous TcHTE in the different life cycle stages of the parasite in order to gain insight in its function in heme transport and homeostasis. We have confirmed that TcHTE is predominantly detected in replicative stages (epimastigote and amastigote). We have also demonstrated that T. cruzi epimastigotes can sense intracellular heme content by an unknown mechanism and regulates heme transport to adapt to changing conditions. Based on these results, we propose a model in which T. cruzi senses intracellular heme and regulates heme transport activity adjusting the expression of TcHTE. The elucidation and characterization of heme transport and homeostasis will contribute to a better understanding of T. cruzi biology as well as other trypanosomatids, pointing out this pathway as a novel drug target for therapeutics.

biochemistry↗