Polyamine metabolism and autophagy in the Trypanosoma cruzi‐host cell interplay

ROMANO PATRICIA SILVIA

Buenos Aires

Conferencia; Buenos Aires Conferences 2013; 2013

Facultad de Medicina. Universidad de Buenos Aires

Autophagy is a cell process implicated in many physiological and pathological situations, even during the infection by intracellular pathogens. Although many compounds are currently used to modulate autophagy, many of them are nonspecific and potentially toxic. Recently it was demonstrated that the polyamine spermidine is a physiological inducer of autophagy. Otherwise, autophagy induction significantly increases host cell colonization by T. cruzi, the etiological agent of Chagas disease. In this study we have characterized the effect of polyamine depletion on autophagy and T. cruzi infectivity. Our data show that spermidine depletion by treatment of cells with the ornithine decarboxylase inhibitor difluoromethylornithine (DFMO) suppressed the autophagic response to starvation and rapamycin treatment. This effect was associated with a decrease in the levels of the autophagic proteins LC3 and ATG5. Moreover, as a consequence of inhibiting host cell autophagy, DFMO impaired T. cruzi infection under autophagy induced or even control conditions. Thus, our results point to DFMO as a novel autophagy inhibitor that may have value in limiting autophagy and the spread of the infection in Chagas disease and possibly other pathological settings.