The role of the Trypanosoma cruzi enzyme L-threonine 3-dehydrogenase in combating stressful environments

Abstract

Trypanosoma cruzi is a digenetic parasite that undergoes various transformations to complete its life cycle. Changes between hosts and vectors involve exposure to stressful environments, for which it has developed different strategies to cope with such stress. L-threonine 3-dehydrogenase (TDH) is a key enzyme in trypanosome metabolism, and several studies have shown that inhibiting TDH affects parasite survival. To understand the role of TDH in T. cruzi, we investigated its expression in different benznidazole (Bz)-resistant clones and overexpressed it in a Bz-susceptible clone. After overexpressing TDH and exposing it to reactive oxygen species (ROS), alkylating agents, and drugs such as Bz, we evaluated certain biological parameters. Our results show that TDH led to higher survival rates when exposed to H2O2 and increased tolerance to Bz. Moreover, the parasites were able to infect more cells, and their mitochondrial membrane potential ({Psi}m) remained unchanged, both of which are linked to higher tolerance to ROS. Finally, parasites overexpressing TDH were less vulnerable to genetic damage caused by agents such as MMS and gamma radiation. Overall, our results demonstrate that TDH, a key enzyme in threonine metabolism, helps combat stressful environments and, under certain experimental conditions, supports the survival of parasites.