Participation of autophagy and polyamines on Trypanosoma cruzi differentiation processes.

MARÍA CRISTINA VANRELL

Encuentro; Young Scientist Program; 2015

T. cruzi, the etiologic agent of Chagas disease adopts different forms during its biology cycle. In the vector gut, Triatoma infestans, the replicative epimastigote form (E) differentiates into infective metacyclic trypomastigotes (MT) in a process called metacyclogenesis. Trypomastigotes (T) can invade a wide range of nucleated cells passing to amastigote form (A) in the host cells. Due to amastigotes are the intracellular replicative form of T. cruzi, amastigogenesis is crucial to continue the parasitic cycle. Although the mechanisms that govern these changes are little know, it has been accepted that low nutrient levels are one of the major stimulus during E to MT differentiation. Autophagy is an intracellular process mainly activated under starvation conditions. On the other hand, polyamines (PA) are ubiquitous polycations that participate in multiple known and unknown biological processes, including autophagy induction. Previously results from our lab have shown by different approaches that E subjected to metacyclogenesis exhibits high number of autophagic-like compartments. In this work, we have studied the effect of PA and other modulators of autophagy during E to MT and T to A differentiation of T. cruzi. Our data show that autophagy inducers significantly increase both processes whereas inhibitors such as wortmannin reduce this response. Furthermore, a T. cruzi mutant that produces endogenous PA displays more autophagic activity and differentiation capacity. From these results we can conclude that autophagy is required during both T. cruzi differentiation processes and that PA are key players activating it.