Krishnan Aarti, Soldati-Favre Dominique
Department of Microbiology and Molecular Medicine, University of Geneva, CMU, Rue Michel-Servet 1, 1211 Geneva, Switzerland.
Metabolites. 2021 Jan 20;11(2):61. doi: 10.3390/metabo11020061.
Obligate intracellular pathogens have coevolved with their host, leading to clever strategies to access nutrients, to combat the host's immune response, and to establish a safe niche for intracellular replication. The host, on the other hand, has also developed ways to restrict the replication of invaders by limiting access to nutrients required for pathogen survival. In this review, we describe the recent advancements in both computational methods and high-throughput -omics techniques that have been used to study and interrogate metabolic functions in the context of intracellular parasitism. Specifically, we cover the current knowledge on the presence of amino acid biosynthesis and uptake within the Apicomplexa phylum, focusing on human-infecting pathogens: and . Given the complex multi-host lifecycle of these pathogens, we hypothesize that amino acids are made, rather than acquired, depending on the host niche. We summarize the stage specificities of enzymes revealed through transcriptomics data, the relevance of amino acids for parasite pathogenesis in vivo, and the role of their transporters. Targeting one or more of these pathways may lead to a deeper understanding of the specific contributions of biosynthesis versus acquisition of amino acids and to design better intervention strategies against the apicomplexan parasites.
专性细胞内病原体与其宿主共同进化,从而形成了获取营养、对抗宿主免疫反应以及为细胞内复制建立安全微环境的巧妙策略。另一方面,宿主也已开发出通过限制病原体生存所需营养物质的获取来限制入侵者复制的方法。在本综述中,我们描述了用于在细胞内寄生环境中研究和探究代谢功能的计算方法和高通量组学技术的最新进展。具体而言,我们涵盖了关于顶复门内氨基酸生物合成和摄取情况的当前知识,重点关注感染人类的病原体: 和 。鉴于这些病原体复杂的多宿主生命周期,我们推测氨基酸是根据宿主微环境合成而非获取的。我们总结了通过转录组学数据揭示的酶的阶段特异性、氨基酸在体内对寄生虫致病作用的相关性以及它们转运蛋白的作用。针对这些途径中的一种或多种可能会使我们更深入地了解氨基酸生物合成与获取的具体作用,并设计出更好的针对顶复门寄生虫的干预策略。