Transcriptomic response to different heme sources in Trypanosoma cruzi epimastigotes

Abstract

Heme is an essential molecule for most organisms, yet someparasites, 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 insectvector, T. cruzi epimastigotes are exposed to both hemoglobin (Hb) andfree heme resulting from its degradation. Despite the importance of thisnutrient, how different heme sources influence parasite gene expressionremains poorly understood.Here, we showed that heme restitution either as hemin or Hb to hemestarvedparasites induces an early and distinct transcriptional responsein T. cruzi epimastigotes. Using RNA sequencing at 4- and 24-hours postsupplementation,we identified gene subsets commonly or uniquely regulatedby each heme source, including genes putatively linked to hemeacquisition and metabolism. The study includes the first focused characterizationof CRAL/TRIO domain-containing protein (TcCRAL/TRIO), anovel heme-responsive hemoprotein. Our results provide a more detailedpicture of T. cruzi biology and highlights heme acquisition as a promisingpoint of vulnerability to control parasite proliferation.