Retooling Leishmania metabolism:: from sand fly gut to human macrophage
Retooling Leishmania metabolism:: from sand fly gut to human macrophage
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DOI：
10.1096/fj.07-9254com
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发表时间：
2008-02-01
期刊：
影响因子：
4.8
通讯作者：
Zilberstein, Dan
中科院分区：
文献类型：
--
作者：
Rosenzweig, Doron;Smith, Derek;Zilberstein, Dan
为了在非常不同的环境中生存，细胞内寄生虫需要高度适应的生理和代谢系统。杜氏利什曼原虫胞外前鞭毛虫生活在沙蝇媒介消化道富含葡萄糖、略有碱性的环境中。在进入人巨噬细胞吞噬溶酶体后，前鞭毛体分化为细胞内的无鞭毛体。这些都能适应酸性环境，在那里葡萄糖稀少，而氨基酸丰富。在这里，我们使用无菌分化模型和一种新的高覆盖率的比较蛋白质组学方法来详细分析分化过程中蛋白质表达的变化。该分析在分化过程中的7个时间点鉴定和量化了21%的寄生虫蛋白质组。数据显示糖异生酶的延迟增加，与糖酵解能力的下降相吻合。同时，β-氧化、氨基酸分解代谢、三羧酸循环、线粒体呼吸链和氧化磷酸化能力都被上调。结果表明，分化型寄生虫由葡萄糖向以脂肪酸和氨基酸为主要能量来源转变。此外，甘油和氨基酸被用作糖合成的前体，弥补了外源糖的缺乏。这些变化发生在前鞭毛体进行形态转换的过程中。我们的发现为单细胞生物体在发育过程中发生的变化提供了新的见解。
To survive extremely different environments, intracellular parasites require highly adaptable physiological and metabolic systems. Leishmania donovani extracellular promastigotes reside in a glucose-rich, slightly alkaline environment in the sand fly vector alimentary tract. On entry into human macrophage phagolysosomes, promastigotes differentiate into intracellular amastigotes. These cope with an acidic milieu, where glucose is scarce while amino acids are abundant. Here, we use an axenic differentiation model and a novel high-coverage, comparative proteomic methodology to analyze in detail protein expression changes throughout the differentiation process. The analysis identified and quantified 21% of the parasite proteome across 7 time points during differentiation. The data reveal a delayed increase in gluconeogenesis enzymes, coinciding with a decrease in glycolytic capacity. At the same time, beta-oxidation, amino acid catabolism, tricarboxylic acid cycle, mitochondrial respiration chain, and oxidative phosphorylation capacities are all up-regulated. The results indicate that the differentiating parasite shifts from glucose to fatty acids and amino acids as its main energy source. Furthermore, glycerol and amino acids are used as precursors for sugar synthesis, compensating for lack of exogenous sugars. These changes occur while promastigotes undergo morphological transformation. Our findings provide new insight into changes occurring in single-cell organisms during a developmental process.