Transcriptomic response to different heme sources in Trypanosoma cruzi epimastigotes

Authors:

Evelyn Tevere1,a, María G. Mediavilla1,a, Cecilia B. Di Capua1, Marcelo L. Merli1, Carlos Robello2,3, Luisa Berná2,4 and Julia A. Cricco

doi: 10.15698/mic2026.01.865
Volume 13, pp. 13 to 27, published 23/01/2026.

Affiliations:

1 Instituto de Biología Molecular y Celular de Rosario (IBR), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)— Universidad Nacional de Rosario (UNR), Rosario, Argentina. 2 Laboratorio de Interacciones Hospedero-patógeno — UBM, Institut Pasteur de Montevideo, Montevideo, Uruguay. 3 Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. 4 Laboratory of Apicomplexan Biology, Institut Pasteur de Montevideo, Uruguay. 5 Bioinformatic Unit, Institut Pasteur de Montevideo, Uruguay. 6 Laboratorio de Genómica Evolutiva, Facultad de Ciencias, Universidad de la República, Uruguay.

a Equal contribution as first authors.

Keywords: 

Chagas disease, Trypanosoma cruzi, heme, hemoglobin, transcriptome

Corresponding Author(s):

Julia A. Cricco , cricco@ibr-conicet.gov.ar

Conflict of interest statement:

The authors declare no conflict of interest.

Please cite this article as:

Evelyn Tevere, María G. Mediavilla, Cecilia B. Di Capua, Marcelo L. Merli, Carlos Robello, Luisa Berná, Julia A. Cricco (2026). Transcriptomic response to different heme sources in Trypanosoma cruzi epimastigotes. Microbial Cell 13: 13-27. doi: 10.15698/mic2026.01.865

© 2026 Tevere et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.

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.