Overexpression of Trypanosoma cruzi High Mobility Group B protein (TcHMGB) alters the nuclear structure, impairs cytokinesis and reduces the parasite infectivity

Kinetoplastid parasites, included Trypanosoma cruzi , the causal agent of Chagas disease, present a unique genome organization and gene expression. Although they control gene expression mainly post-transcriptionally, chromatin accessibility plays a fundamental role in transcription initiation control. We have previously shown that High Mobility Group B protein from Trypanosoma cruzi ( Tc HMGB) can bind DNA in vitro . Here, we show that Tc HMGB also acts as an architectural protein in vivo , since the overexpression of this protein induces changes in the nuclear structure, mainly the reduction of the nucleolus and a decrease in the heterochromatin:euchromatin ratio. Epimastigote replication rate was markedly reduced presumably due to a delayed cell cycle progression with accumulation of parasites in G2/M phase and impaired cytokinesis. Some functions involved in pathogenesis were also altered in Tc HMGB-overexpressing parasites, like the decreased efficiency of trypomastigotes to infect cells in vitro , the reduction of intracellular amastigotes replication and the number of released trypomastigotes. Taken together, our results suggest that the Tc HMGB protein is a pleiotropic player that controls cell phenotype and it is involved in key cellular processes.