Edited by Chris WhitfieldTrypanosoma cruzi, the etiological agent of Chagas disease, is a protozoan parasite with a complex life cycle involving a triatomine insect and mammals. Throughout its life cycle, the T. cruzi parasite faces several alternating events of cell division and cell differentiation in which exponential and stationary growth phases play key biological roles. It is well accepted that arrest of the cell division in the epimastigote stage, both in the midgut of the triatomine insect and in vitro, is required for metacyclogenesis, and it has been previously shown that the parasites change the expression profile of several proteins when entering this quiescent stage. However, little is known about the metabolic changes that epimastigotes undergo before they develop into the metacyclic trypomastigote stage. We applied targeted metabolomics to measure the metabolic intermediates in the most relevant pathways for energy metabolism and oxidative imbalance in exponentially growing and stationary growth-arrested epimastigote parasites. We show for the first time that T. cruzi epimastigotes transitioning from the exponential to the stationary phase exhibit a finely tuned adaptive metabolic mechanism that enables switching from glucose to amino acid consumption, which is more abundant in the stationary phase. This metabolic plasticity appears to be crucial for survival of the T. cruzi parasite in the myriad different environmental conditions to which it is exposed during its life cycle.Cell growth, both in natural environments or in in vitro culture, usually presents in two phases: the exponential phase where cells divide at a roughly constant rate, and the stationary phase where cells slow down or stop the cell cycle and division. During the exponential phase, cells go through the well described canonical cell cycle of G 1 3 S 3 G 2 3 M. In the stationary phase, cells leave the regular cell cycle to enter a resting state known as quiescence, which is highly relevant because it corresponds to the physiological state in which most cells from both unicellular and multicellular organisms spend most of their life (1).Trypanosoma cruzi, the etiological agent of Chagas disease, is a protozoan parasite with a complex life cycle involving a triatomine insect and mammals. Throughout its life cycle, the T. cruzi parasite faces several alternated events of cell division and cell differentiation. Briefly, insects are infected during a blood meal from a mammal having non-dividing forms of the parasite, denominated trypomastigotes, present in their blood. Once in the midgut of the triatomine insect, the trypomastigotes differentiate to replicative non-infective epimastigotes, which proliferate and colonize the digestive tube. After the blood meal, nutrients are consumed by the intestinal epithelium, the parasite, and the intestinal microbiota population; therefore, the replicative epimastigotes eventually face nutrient starvation. Under this situation of metabolic stress, cell division is arrested, and the parasites adhe...
