Effects of Histone deacetylation inhibitors on T. cruzi replication, differentiation, infectivity and gene expression

CAMPO VA; FRASCH, ALBERTO C. C.

Buenos Aires

Congreso; Molecular mechanisms in cell signaling and gene expression; 2013

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Epigenetic events like acetylation and deacetylation of histones affect gene expression in protozoan parasites such as T. brucei and P. falciparum. Here we show the effect of histone deacetylases inhibitors (HDACis) on T. cruzi differentiation, replication, infectivity and gene expression. We found that epimastigotes replication rate is barely affected after treatment with inhibitors Trichostatin A (TSA), Apicidin (Api), Sirtinol (Sir) and Nicotinamide (Nic). Differentiation to metacyclic trypomastioges forms was inhibited with all HDACis tested, but differentiation to amastigote forms was not affected. Also, pre-incubation of cell derived trypomastigote with TSA, Api and Sir produced a 10% increase on in vitro infections, but the opposite effect was observed with Nicotinamide. Finally, we tested the effects of Api on trypomastigote gene expression. We found a two fold increase for Bromodomain factor 2 and two T. cruzi HDACs transcripts. Genes coding for cell cycle division, cell programmed death proteins, PCNA and a Trypomastigote surface antigen decreased to half comparing to control parasites. These results show that enrichment in acetylated histones derived from HDACis treatment is sufficient to produce changes on gene expression, affecting differentiation and infectivity thus suggesting that this epigenetic event may play a role in controlling transcription rate in T. cruzi.