Metabolomic profiling reveals a finely tuned, starvation-induced metabolic switch in Trypanosoma cruzi epimastigotes
Metabolomic profiling reveals a finely tuned, starvation-induced metabolic switch in Trypanosoma cruzi epimastigotes
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DOI：
10.1074/jbc.m117.778522
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发表时间：
2017-05-26
影响因子：
4.8
通讯作者：
Cassera, Maria Belen
中科院分区：
文献类型：
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作者：
Barison, Maria Julia;Rapado, Ludmila Nakamura;Cassera, Maria Belen
克氏锥虫是恰加斯病的病原，是一种具有复杂生命周期的原生动物寄生虫，涉及锥虫和哺乳动物。在整个生命周期中，克氏锥虫面临着细胞分裂和细胞分化的几个交替事件，其中指数生长和平稳生长阶段起着关键的生物学作用。人们普遍认为，无论是在三角蝽昆虫的中肠还是在体外，在附生毛囊阶段，细胞分裂的停止都是细胞形成所必需的。以前的研究表明，寄生虫在进入这一静止阶段时改变了几种蛋白质的表达谱。然而，在它们发展到元环锥马鞭毛体阶段之前，我们对它们所经历的代谢变化知之甚少。我们应用靶向代谢组学技术测量了指数生长和停滞生长的附马马体虫中能量代谢和氧化失衡最相关途径中的代谢中间体。我们首次表明，从指数期过渡到固定期的克氏T.克氏黏液菌表现出一种精细调节的适应性代谢机制，能够从葡萄糖消耗转换到氨基酸消耗，而氨基酸消耗在固定期更为丰富。这种代谢可塑性似乎对克氏锥虫在其生命周期中所暴露的无数不同环境条件下的生存至关重要。
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 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.