Trypanosoma brucei, as well as Trypanosoma cruzi and more than 20 species of the genus Leishmania, form a group of flagellated protists that threaten human health. These organisms are transmitted by insects that, together with mammals, are their natural hosts. This implies that during their life cycles each of them faces environments with different physical, chemical, biochemical, and biological characteristics. In this work we review how amino acids are obtained from such environments, how they are metabolized, and how they and some of their intermediate metabolites are used as a survival toolbox to cope with the different conditions in which these parasites should establish the infections in the insects and mammalian hosts.

Trypanosoma cruzi, the parasite causing Chagas disease, is a digenetic flagellated protist that infects mammals (including humans) and reduviid insect vectors. Therefore, T. cruzi must colonize different niches in order to complete its life cycle in both hosts. This fact determines the need of adaptations to face challenging environmental cues. The primary environmental challenge, particularly in the insect stages, is poor nutrient availability. In this regard, it is well known that T. cruzi has a flexible metabolism able to rapidly switch from carbohydrates (mainly glucose) to amino acids (mostly proline) consumption. Also established has been the capability of T. cruzi to use glucose and amino acids to support the differentiation process occurring in the insect, from replicative non-infective epimastigotes to non-replicative infective metacyclic trypomastigotes. However, little is known about the possibilities of using externally available and internally stored fatty acids as resources to survive in nutrient-poor environments, and to sustain metacyclogenesis. In this study, we revisit the metabolic fate of fatty acid breakdown in T. cruzi. Herein, we show that during parasite proliferation, the glucose concentration in the medium can regulate the fatty acid metabolism. At the stationary phase, the parasites fully oxidize fatty acids. [U-¹⁴C]-palmitate can be taken up from the medium, leading to CO₂ production. Additionally, we show that electrons are fed directly to oxidative phosphorylation, and acetyl-CoA is supplied to the tricarboxylic acid (TCA) cycle, which can be used to feed anabolic pathways such as the de novo biosynthesis of fatty acids. Finally, we show as well that the inhibition of fatty acids mobilization into the mitochondrion diminishes the survival to severe starvation, and impairs metacyclogenesis.

Acute diarrhea is the second leading cause of death among children in developing countries and is strongly related with the socioeconomic conditions of the population. In Brazil, data show a drop in the diarrhea mortality rate. Nevertheless, the northeastern region still has the most deaths. Considering this, we analyze high-risk areas for diarrhea- and gastroenteritis-related deaths, and their association with social determinants of health (SDH) in the state with one of the worst human development indicators in Brazil (Alagoas) between 2000 and 2019. We applied temporal, spatial, and space–time risk modelling. We used a log-linear regression model to assess temporal trends and the local empirical Bayesian estimator, the global and local Moran indices for spatial analysis. Spearman’s correlation was used to correlate mortality rates with SDH. A total of 3472 diarrhea-related deaths were reported during this period in Alagoas. We observed a decreasing time trend of deaths in the state (9.41/100,000 in 2000 to 2.21 in 2019; APC = −6.7; p-value < 0.001), especially in children under one year of age. However, there was stability among adults and the elderly. We identified two high-risk spatiotemporal clusters of mortality in inland municipalities. Lastly, mortality rates correlated significantly with 90% of SDH. Taken together, these findings indicate that diarrhea diseases remain a serious public health concern in Alagoas, mainly in the poorest and inland municipalities. Thereby, it is urgently necessary to invest in measures to control and prevent cases, and improve the living conditions of the poorest populations and those with the highest social vulnerability index.

Trypanosoma cruzi is the aetiologic agent of Chagas disease, which affects people in the Americas and worldwide. The parasite has a complex life cycle that alternates among mammalian hosts and insect vectors. During its life cycle, T. cruzi passes through different environments and faces nutrient shortages. It has been established that amino acids, such as proline, histidine, alanine, and glutamate, are crucial to T. cruzi survival. Recently, we described that T. cruzi can biosynthesize glutamine from glutamate and/or obtain it from the extracellular environment, and the role of glutamine in energetic metabolism and metacyclogenesis was demonstrated. In this study, we analysed the effect of glutamine analogues on the parasite life cycle. Here, we show that glutamine analogues impair cell proliferation, the developmental cycle during the infection of mammalian host cells and metacyclogenesis. Taken together, these results show that glutamine is an important metabolite for T. cruzi survival and suggest that glutamine analogues can be used as scaffolds for the development of new trypanocidal drugs. These data also reinforce the supposition that glutamine metabolism is an unexplored possible therapeutic target.