Kifle Desalegn Woldeyohannes, Pearson Mark S, Becker Luke, Pickering Darren, Loukas Alex, Sotillo Javier
Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, 4878, Queensland, Australia; Aklilu Lemma Institute of Pathobiology, Addis Ababa University, 1176, Addis Ababa, Ethiopia.
Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, 4878, Queensland, Australia.
Mol Biochem Parasitol. 2020 Mar;236:111264. doi: 10.1016/j.molbiopara.2020.111264. Epub 2020 Jan 31.
Helminth parasites secrete extracellular vesicles (EVs) into their environment that have potential roles in host-parasite communication, and thus represent potentially useful targets for novel control strategies. Here, we carried out a comprehensive proteomic analysis of two different populations of EVs - 15k pellet and 120k pellet EVs - from Schistosoma mansoni adult worms. We characterised the proteins present in the membranes of the EVs (including external trypsin-liberated peptides, integral membrane proteins (IMPs) and peripheral membrane proteins (PMPs)), as well as cargo proteins, using LC-MS/MS. A total of 286 and 716 proteins were identified in 15k and 120k pellets, respectively. Some of the most abundant proteins identified from both 15k and 120k pellets include known vaccine candidates such as Sm-TSP-2, saponin B domain-containing proteins, calpain glutathione-S-transferase, Sm29 and cathepsin domain-containing proteins. Other abundant proteins that have not been tested as vaccines include DM9 domain-containing protein, 13 kDa tegumental antigen and histone H4-like protein. Sm23, a member of the tetraspanin family with known vaccine efficacy, was identified in the cargo and IMP compartments of only 15k pellet vesicles. Moreover, a collection of proteins with known or potential relevance in host-parasite communication including proteases, antioxidants and EV biogenesis/trafficking of both vesicle types were identified. Our results provide the first report of a comprehensive compartmental proteomic analysis of adult S. mansoni-derived EVs. Future research should investigate recombinant forms of these proteins as vaccine and serodiagnostic antigens as well as the roles of EV proteins in host-parasite communication.
蠕虫寄生虫会向其生存环境中分泌细胞外囊泡（EVs），这些囊泡在宿主与寄生虫的交流中可能发挥作用，因此是新型控制策略潜在的有用靶点。在此，我们对来自曼氏血吸虫成虫的两种不同群体的细胞外囊泡——15k沉淀囊泡和120k沉淀囊泡进行了全面的蛋白质组学分析。我们使用液相色谱-串联质谱法（LC-MS/MS）对细胞外囊泡膜中存在的蛋白质（包括外部胰蛋白酶释放的肽、整合膜蛋白（IMPs）和外周膜蛋白（PMPs））以及货物蛋白进行了表征。在15k和120k沉淀中分别鉴定出了286种和716种蛋白质。从15k和120k沉淀中鉴定出的一些最丰富的蛋白质包括已知的疫苗候选物，如Sm-TSP-2、含皂苷B结构域的蛋白质、钙蛋白酶谷胱甘肽-S-转移酶、Sm29和含组织蛋白酶结构域的蛋白质。其他尚未作为疫苗进行测试的丰富蛋白质包括含DM9结构域的蛋白质、13 kDa体壁抗原和组蛋白H4样蛋白。Sm23是具有已知疫苗效力的四跨膜蛋白家族成员，仅在15k沉淀囊泡的货物和IMPs区室中被鉴定出来。此外，还鉴定出了一系列在宿主与寄生虫交流中具有已知或潜在相关性的蛋白质，包括蛋白酶、抗氧化剂以及两种囊泡类型的细胞外囊泡生物发生/运输相关蛋白。我们的结果首次报道了对曼氏血吸虫成虫来源的细胞外囊泡进行的全面区室蛋白质组学分析。未来的研究应调查这些蛋白质的重组形式作为疫苗和血清诊断抗原，以及细胞外囊泡蛋白在宿主与寄生虫交流中的作用。
