Laboratory of Biochemistry of Tryps-LaBTryps, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 1374, 05508000 Sao Paulo, Brazil.
Molecules. 2020 Apr 2;25(7):1628. doi: 10.3390/molecules25071628.
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, 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 survival. Recently, we described that 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 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.
克氏锥虫是恰加斯病的病原体，影响着美洲和世界各地的人群。寄生虫具有复杂的生命周期，在哺乳动物宿主和昆虫媒介之间交替。在其生命周期中，克氏锥虫会经历不同的环境并面临营养短缺。已经确定，氨基酸（如脯氨酸、组氨酸、丙氨酸和谷氨酸）对克氏锥虫的生存至关重要。最近，我们描述了克氏锥虫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谷氨酰胺，并且谷氨酰胺在能量代谢和循环转化中发挥作用。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。结果表明，谷氨酰胺类似物会损害细胞增殖、哺乳动物宿主细胞感染过程中的发育周期和循环转化。综上所述，这些结果表明谷氨酰胺是克氏锥虫生存的重要代谢物，并提示谷氨酰胺类似物可以作为开发新型杀锥虫药物的支架。这些数据还进一步证实了谷氨酰胺代谢是一个未被探索的潜在治疗靶点。
