Centre for Immunity, Infection and Evolution and Centre for Translational and Chemical Biology, School of Biological Sciences, The University of Edinburgh, Edinburgh, United Kingdom.
Laboratoire de Microbiologie Fondamentale et Pathogénicité (MFP), Université de Bordeaux, CNRS UMR-5234, France.
Exp Parasitol. 2021 May;224:108102. doi: 10.1016/j.exppara.2021.108102. Epub 2021 Mar 26.
The human pathogenic trypanosomatid species collectively called the "TriTryp parasites" - Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp. - have complex life cycles, with each of these parasitic protists residing in a different niche during their successive developmental stages where they encounter diverse nutrients. Consequently, they adapt their metabolic network accordingly. Yet, throughout the life cycles, carbohydrate metabolism - involving the glycolytic, gluconeogenic and pentose-phosphate pathways - always plays a central role in the biology of these parasites, whether the available carbon and free energy sources are saccharides, amino acids or lipids. In this paper, we provide an updated review of the carbohydrate metabolism of the TriTryps, highlighting new data about this metabolic network, the interconnection of its pathways and the compartmentalisation of its enzymes within glycosomes, cytosol and mitochondrion. Differences in the expression of the branches of the metabolic network between the successive life-cycle stages of each of these parasitic trypanosomatids are discussed, as well as differences between them. Recent structural and kinetic studies have revealed unique regulatory mechanisms for some of the network's key enzymes with important species-specific variations. Furthermore, reports of multiple post-translational modifications of trypanosomal glycolytic enzymes suggest that additional mechanisms for stage- and/or environmental cues that regulate activity are operational in the parasites. The detailed comparison of the carbohydrate metabolism of the TriTryps has thus revealed multiple differences and a greater complexity, including for the reduced metabolic network in bloodstream-form T. brucei, than previously appreciated. Although these parasites are related, share many cytological and metabolic features and are grouped within a single taxonomic family, the differences highlighted in this review reflect their separate evolutionary tracks from a common ancestor to the extant organisms. These differences are indicative of their adaptation to the different insect vectors and niches occupied in their mammalian hosts.
人类病原体原生动物物种统称为“三鞭毛寄生虫” - 布氏锥虫、克氏锥虫和利什曼原虫属。 - 具有复杂的生命周期，这些寄生原生动物在其连续发育阶段中分别存在于不同的小生境中，在那里它们遇到不同的营养物质。因此，它们相应地调整了它们的代谢网络。然而，在整个生命周期中，碳水化合物代谢 - 涉及糖酵解、糖异生和戊糖磷酸途径 - 在这些寄生虫的生物学中始终起着核心作用，无论可用的碳和自由能源来源是糖、氨基酸还是脂质。在本文中，我们提供了对三鞭毛寄生虫碳水化合物代谢的最新综述，强调了有关该代谢网络、其途径的相互连接以及其酶在糖体、细胞质和线粒体中的区室化的新数据。讨论了这些寄生原生动物的每个连续生命周期阶段的代谢网络分支的表达差异，以及它们之间的差异。最近的结构和动力学研究揭示了一些网络关键酶的独特调节机制，具有重要的种特异性变化。此外，报道了多个糖酵解酶的翻译后修饰，表明在寄生虫中存在调节活性的阶段和/或环境线索的其他机制。因此，对三鞭毛寄生虫碳水化合物代谢的详细比较揭示了多种差异和更高的复杂性，包括血液阶段 T. brucei 的简化代谢网络，比以前的认识更为复杂。尽管这些寄生虫是相关的，具有许多细胞学和代谢特征，并被归类在单一的分类科内，但本综述中强调的差异反映了它们从共同祖先到现存生物的独立进化轨迹。这些差异表明它们适应了不同的昆虫媒介和在哺乳动物宿主中占据的小生境。
