# Transcriptomic response to different heme sources in Trypanosoma cruzi epimastigotes

## TL;DR

This study explores how Trypanosoma cruzi parasites respond to different heme sources, revealing distinct gene expression patterns and a new heme-responsive protein.

## Contribution

The first focused characterization of a novel heme-responsive hemoprotein in T. cruzi and distinct transcriptional responses to heme sources.

## Key findings

- Heme restitution as hemin or hemoglobin induces distinct transcriptional responses in T. cruzi epimastigotes.
- RNA sequencing identified gene subsets regulated by each heme source, including those linked to heme acquisition and metabolism.
- A novel heme-responsive hemoprotein, TcCRAL/TRIO, was characterized for the first time in this study.

## Abstract

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. The study includes the first focused characterization of CRAL/TRIO domain-containing protein (TcCRAL/TRIO), a novel heme-responsive hemoprotein. Our results provide a more detailed picture of T. cruzi biology and highlights heme acquisition as a promising point of vulnerability to control parasite proliferation.