Bennett Adam P S, Robinson Mark W
School of Biological Sciences, Queen's University Belfast, 19 Chlorine Gardens, Belfast BT9 5DL, Northern Ireland, UK.
Pathogens. 2021 Mar 16;10(3):348. doi: 10.3390/pathogens10030348.
Trematodes cause disease in millions of people worldwide, but the absence of commercial vaccines has led to an over-reliance on a handful of monotherapies to control infections. Since drug-resistant fluke populations are emerging, a deeper understanding of parasite biology and host interactions is required to identify new drug targets and immunogenic vaccine candidates. Mass spectrometry-based proteomics represents a key tool to that end. Recent studies have capitalised on the wider availability of annotated helminth genomes to achieve greater coverage of trematode proteomes and discover new aspects of the host-parasite relationship. This review focusses on these latest advances. These include how the protein components of fluke extracellular vesicles have given insight into their biogenesis and cellular interactions. In addition, how the integration of transcriptome/proteome datasets has revealed that the expression and secretion of selected families of liver fluke virulence factors and immunomodulators are regulated in accordance with parasite development and migration within the mammalian host. Furthermore, we discuss the use of immunoproteomics as a tool to identify vaccine candidates associated with protective antibody responses. Finally, we highlight how established and emerging technologies, such as laser microdissection and single-cell proteomics, could be exploited to resolve the protein profiles of discrete trematode tissues or cell types which, in combination with functional tools, could pinpoint optimal targets for fluke control.
吸虫在全球范围内导致数百万人患病，但由于缺乏商业疫苗，人们过度依赖少数几种单一疗法来控制感染。鉴于耐药吸虫种群不断出现，需要更深入地了解寄生虫生物学和宿主相互作用，以确定新的药物靶点和具有免疫原性的疫苗候选物。基于质谱的蛋白质组学是实现这一目标的关键工具。最近的研究利用已注释的蠕虫基因组的更广泛可得性，以实现吸虫蛋白质组的更大覆盖范围，并发现宿主 - 寄生虫关系的新方面。本综述聚焦于这些最新进展。这些进展包括吸虫细胞外囊泡的蛋白质成分如何为其生物发生和细胞相互作用提供了见解。此外，转录组/蛋白质组数据集的整合如何揭示了肝吸虫毒力因子和免疫调节剂特定家族的表达和分泌是根据寄生虫在哺乳动物宿主体内的发育和迁移进行调节的。此外，我们讨论了免疫蛋白质组学作为一种工具来鉴定与保护性抗体反应相关的疫苗候选物的用途。最后，我们强调如何利用已有的和新兴的技术，如激光显微切割和单细胞蛋白质组学，来解析离散的吸虫组织或细胞类型的蛋白质谱，这些技术与功能工具相结合，可以确定吸虫控制的最佳靶点。
