Proliferation and Differentiation of Trypanosoma cruzi inside Its Vector Have a New Trigger: Redox Status

Abstract

Trypanosoma cruzi proliferate and differentiate inside different compartments of triatomines gut that is the first environment encountered by T. cruzi. Due to its complex life cycle, the parasite is constantly exposed to reactive oxygen species (ROS). We tested the influence of the pro-oxidant molecules H2O2 and the superoxide generator, Paraquat, as well as, metabolism products of the vector, with distinct redox status, in the proliferation and metacyclogenesis. These molecules are heme, hemozoin and urate. We also tested the antioxidants NAC and GSH. Heme induced the proliferation of epimastigotes and impaired the metacyclogenesis. β-hematin, did not affect epimastigote proliferation but decreased parasite differentiation. Conversely, we show that urate, GSH and NAC dramatically impaired epimastigote proliferation and during metacyclogenesis, NAC and urate induced a significant increment of trypomastigotes and decreased the percentage of epimastigotes. We also quantified the parasite loads in the anterior and posterior midguts and in the rectum of the vector by qPCR. The treatment with the antioxidants increased the parasite loads in all midgut sections analyzed. In vivo, the group of vectors fed with reduced molecules showed an increment of trypomastigotes and decreased epimastigotes when analyzed by differential counting. Heme stimulated proliferation by increasing the cell number in the S and G2/M phases, whereas NAC arrested epimastigotes in G1 phase. NAC greatly increased the percentage of trypomastigotes. Taken together, these data show a shift in the triatomine gut microenvironment caused by the redox status may also influence T. cruzi biology inside the vector. In this scenario, oxidants act to turn on epimastigote proliferation while antioxidants seem to switch the cycle towards metacyclogenesis. This is a new insight that defines a key role for redox metabolism in governing the parasitic life cycle.

Benznidazole induces in vitro anaerobic metabolism in Trypanosoma cruzi epimastigotes

“…The in vitro growth of T. cruzi epimastigotes in LIT cutlure medium has been extensively described in the literature [15][16][17]. Our findings are in accordance with such descriptions.…”

Metabolomic profiling reveals a finely tuned, starvation-induced metabolic switch in Trypanosoma cruzi epimastigotes

“…In addition to the described metabolic uniqueness, our results showed that these processes are differentially used in both phases of epimastigote growth. Interestingly, recently it was suggested that epimastigote proliferation requires an oxidative environment to happen, whereas differentiation occurs in a more reductive setting (34).…”

Trypanosoma cruzi: Morphological and Microtubular Changes Related to Epimastigote Differentiation under Hyperosmotic Stress

“…Several factors have been described as involved in triggering this differentiation, such as availability of nutrients, intracellular cAMP levels and amino acid metabolism (reviewed by Goldenberg and Rodrigues Ávila, [16]) and, more recently, redox status [17]. Although it is known that metacyclogenesis can be induced in vitro by incubating epimastigotes in TAU3AAG, a chemically defined medium that mimics the urine of triatomine bugs [18], the exact events that induce this process are unknown so far.…”