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.

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谷氨酰胺类似物损害克氏锥虫的细胞增殖、细胞内循环和元循环发生

克氏锥虫是南美锥虫病的病原体，该病影响美洲和世界各地的人们。寄生虫具有复杂的生命周期，在哺乳动物宿主和昆虫载体之间交替。在其生命周期中，T. cruzi 经历了不同的环境并面临营养短缺。已经确定氨基酸，例如脯氨酸、组氨酸、丙氨酸和谷氨酸对 T. cruzi 的存活至关重要。最近，我们描述了 T. cruzi 可以从谷氨酸生物合成谷氨酰胺和/或从细胞外环境中获取它，并证明了谷氨酰胺在能量代谢和元环发生中的作用。在这项研究中，我们分析了谷氨酰胺类似物对寄生虫生命周期的影响。在这里，我们表明谷氨酰胺类似物会损害细胞增殖，哺乳动物宿主细胞感染和后形成过程中的发育周期。总之，这些结果表明谷氨酰胺是 T. cruzi 存活的重要代谢物，并表明谷氨酰胺类似物可用作开发新的锥虫杀灭剂药物的支架。这些数据还强化了谷氨酰胺代谢是一个尚未探索的可能治疗靶点的假设。