Both inhibition and activation of histone deacetylase activity affect Trypanosoma cruzi replication, differentiation, infectivity and gene expression

CAMPO, VANINA A.

Buenos Aires

Mesa redonda; Sociedad Argentina de Protozoología XXVII Reunión Anual; 2015

Sociedad Argentina de Protozoología

Histonepost-translational modification, mediated by histone acetyltransferases anddeacetylases, is one of the most studied factors affecting gene expression.Recent data showing differential histone acetylation states during the Trypanosomacruzi cell cycle suggest a role for epigenetics in the control of thisprocess. As a starting point to study the role of histone deacetylases in thecontrol of gene expression and the consequences of their inhibition and activationin the biology of T. cruzi, two inhibitors for different histonedeacetylases: trichostatin A for class I/II and sirtinol for class III and theactivator resveratrol specific for class III, were tested on proliferative andinfective forms of this parasite. The results showed that the two inhibitorstested caused histone hyperacetylation whereas resveratrol showed the oppositeeffect on both parasite forms, indicating that histones are substrates forthese enzymes. Histone deacetylase inhibitors caused life stage-specificeffects, increasing trypomastigotes infectivity and blocking metacyclogenesisin a concentration dependent manner. Moreover, these inhibitors differentiallyaffected specific transcript levels, with sirtinol causing the most pronouncedchange. On the other hand, the HDACs activator resveratrol showed strongeranti-parasitic effects than inhibition. Resveratrol killed the proliferativeforms of the parasite, reduced in vitro infection with a concomitant reductionon the expression of trypomastigotes key surface proteins. In addition, thisdrug blocked differentiation and/or replication of intracellular amastigotes.In conclusion, the data presented here supports the notion that modulation ofthe histones acetylation state plays a role on T. cruzi gene expression.Also, the results presented here point out to Resveratrol as an interestingcandidate for further studies on its anti-parasitic effects.