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曼氏血吸虫童虫体表蛋白的定量蛋白质组学分析揭示了新的潜在治疗靶点。

A quantitative proteomic analysis of the tegumental proteins from Schistosoma mansoni schistosomula reveals novel potential therapeutic targets.

作者信息

Sotillo Javier, Pearson Mark, Becker Luke, Mulvenna Jason, Loukas Alex

机构信息

Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia.

Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia.

出版信息

Int J Parasitol. 2015 Jul;45(8):505-16. doi: 10.1016/j.ijpara.2015.03.004. Epub 2015 Apr 21.

DOI:10.1016/j.ijpara.2015.03.004
PMID:25910674
Abstract

The tegument of Schistosoma mansoni plays an integral role in host-parasite interactions, particularly during the transition from the free-living cercariae to the intra-mammalian schistosomula stages. This developmental period is characterised by the transition from a trilaminate surface to a heptalaminate tegument that plays key roles in immune evasion, nutrition and excretion. Proteins exposed at the surface membranes of newly transformed schistosomula are therefore thought to be prime targets for the development of new vaccines and drugs for schistosomiasis. Using a combination of tegumental labelling and high-throughput quantitative proteomics, more than 450 proteins were identified on the apical membrane of S. mansoni schistosomula, of which 200 had significantly regulated expression profiles at different stages of schistosomula development in vitro, including glucose transporters, sterols, heat shock proteins, antioxidant enzymes and peptidases. Current vaccine antigens were identified on the apical membrane (Sm-TSP-1, calpain) or sub-tegumental (Sm-TSP-2, Sm29) fractions of the schistosomula, displaying localisation patterns that, in some cases, differ from that in the adult stage fluke. This work provides the first known in-depth proteomic analysis of the surface-exposed proteins in the schistosomula tegument, and some of the proteins identified are clear targets for the generation of new vaccines and drugs against schistosomiasis.

摘要

曼氏血吸虫的皮层在宿主-寄生虫相互作用中起着不可或缺的作用,特别是在从自由生活的尾蚴转变为哺乳动物体内的童虫阶段。这个发育时期的特点是从三层表面转变为七层皮层,这在免疫逃避、营养和排泄中起着关键作用。因此,新转化的童虫表面膜上暴露的蛋白质被认为是开发治疗血吸虫病新疫苗和药物的主要靶点。通过结合皮层标记和高通量定量蛋白质组学,在曼氏血吸虫童虫的顶端膜上鉴定出了450多种蛋白质,其中200种在体外童虫发育的不同阶段具有显著调控的表达谱,包括葡萄糖转运蛋白、固醇、热休克蛋白、抗氧化酶和肽酶。目前的疫苗抗原在童虫的顶端膜(Sm-TSP-1、钙蛋白酶)或皮层下(Sm-TSP-2、Sm29)组分中被鉴定出来,其定位模式在某些情况下与成虫期吸虫不同。这项工作首次对童虫皮层表面暴露的蛋白质进行了深入的蛋白质组学分析,并且鉴定出的一些蛋白质显然是开发抗血吸虫病新疫苗和药物的靶点。

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