Swapna Lakshmipuram Seshadri, Parkinson John
a Program in Molecular Structure and Function , Hospital for Sick Children , Toronto , Ontario , Canada.
b Departments of Biochemistry, Molecular Genetics and Computer Science , University of Toronto , Toronto , Ontario , Canada.
Crit Rev Biochem Mol Biol. 2017 Jun;52(3):254-273. doi: 10.1080/10409238.2017.1290043. Epub 2017 Feb 22.
The increasing prevalence of infections involving intracellular apicomplexan parasites such as Plasmodium, Toxoplasma, and Cryptosporidium (the causative agents of malaria, toxoplasmosis, and cryptosporidiosis, respectively) represent a significant global healthcare burden. Despite their significance, few treatments are available; a situation that is likely to deteriorate with the emergence of new resistant strains of parasites. To lay the foundation for programs of drug discovery and vaccine development, genome sequences for many of these organisms have been generated, together with large-scale expression and proteomic datasets. Comparative analyses of these datasets are beginning to identify the molecular innovations supporting both conserved processes mediating fundamental roles in parasite survival and persistence, as well as lineage-specific adaptations associated with divergent life-cycle strategies. The challenge is how best to exploit these data to derive insights into parasite virulence and identify those genes representing the most amenable targets. In this review, we outline genomic datasets currently available for apicomplexans and discuss biological insights that have emerged as a consequence of their analysis. Of particular interest are systems-based resources, focusing on areas of metabolism and host invasion that are opening up opportunities for discovering new therapeutic targets.
涉及细胞内顶复门寄生虫（如疟原虫、弓形虫和隐孢子虫，分别为疟疾、弓形虫病和隐孢子虫病的病原体）的感染日益普遍，这是一个重大的全球医疗负担。尽管它们很重要，但可用的治疗方法却很少；随着新的寄生虫耐药菌株的出现，这种情况可能会恶化。为了为药物发现和疫苗开发计划奠定基础，已经生成了许多此类生物体的基因组序列，以及大规模表达和蛋白质组数据集。对这些数据集的比较分析开始识别支持在寄生虫生存和持续存在中发挥基本作用的保守过程以及与不同生命周期策略相关的谱系特异性适应的分子创新。挑战在于如何最好地利用这些数据来深入了解寄生虫毒力并识别那些最适合作为靶点的基因。在这篇综述中，我们概述了目前可用于顶复门寄生虫的基因组数据集，并讨论了因其分析而产生的生物学见解。特别感兴趣的是基于系统的资源，重点关注代谢和宿主入侵领域，这些领域为发现新的治疗靶点提供了机会。
