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In silico identification of immunotherapeutic and diagnostic targets in the glycosylphosphatidylinositol metabolism of the coccidian Sarcocystis aucheniae.
Transboundary and Emerging Diseases ( IF 3.5 ) Pub Date : 2019-12-27 , DOI: 10.1111/tbed.13438
Cecilia Decker Franco 1, 2 , Sarah N Wieser 1 , Marcelo Soria 2, 3 , Paloma de Alba 1 , Mónica Florin-Christensen 1, 2 , Leonhard Schnittger 1, 2
Affiliation  

Meat of the South American camelids (SACs) llama and alpaca is an important source of animal protein and income for rural families in the Andes, and a product with significant growth potential for local and international markets. However, infestation with macroscopic cysts of the coccidian protozoon Sarcocystis aucheniae, a parasitosis known as SAC sarcocystosis, significantly hampers its commercialization. There are no validated methods to diagnose the presence of S. aucheniae cysts other than carcass examination. Moreover, there are no available drugs or vaccines to cure or prevent SAC sarcocystosis. Identification of relevant molecules that act at the host-pathogen interface can significantly contribute to the control of this disease. It has been shown for other pathogenic protozoa that glycosylphosphatidylinositol (GPI) is a critical molecule implicated in parasite survival and pathogenicity. This study focused on the identification of the enzymes that participate in the S. aucheniae GPI biosynthetic pathway and the repertoire of the parasite GPI-anchored proteins (GPI-APs). To this aim, RNA was extracted from parasite cysts and the transcriptome was sequenced and translated into amino acid sequences. The generated database was mined using sequences of well-characterized GPI biosynthetic enzymes of Saccharomyces cerevisiae and Toxoplasma gondii. Eleven enzymes predicted to participate in the S. aucheniae GPI biosynthetic pathway were identified. On the other hand, the database was searched for proteins carrying an N-terminal signal peptide and a single C-terminal transmembrane region containing a GPI anchor signal. Twenty-four GPI-anchored peptides were identified, of which nine are likely S. aucheniae-specific, and 15 are homologous to membrane proteins of other coccidians. Among the latter, 13 belong to the SRS domain superfamily, an extensive group of coccidian GPI-anchored proteins that mediate parasite interaction with their host. Phylogenetic analysis showed a great degree of intra- and inter-specific divergence among SRS family proteins. In vitro and in vivo experiments are needed to validate S. aucheniae GPI biosynthetic enzymes and GPI-APs as drug targets and/or as vaccine or diagnostic antigens.

中文翻译:

在计算机上鉴定球虫Sarcocystis aucheniae的糖基磷脂酰肌醇代谢中的免疫治疗和诊断靶标。

南美骆驼科动物的羊驼和羊驼的肉是安第斯山脉农村家庭重要的动物蛋白和收入来源,也是一种在本地和国际市场具有巨大增长潜力的产品。但是,球虫子原虫Sarcocystis aucheniae的宏观囊肿(一种被称为SAC囊虫病的寄生虫)的侵害显着阻碍了其商业化。除了car体检查以外,没有经过验证的方法可以诊断存在奥氏假单胞菌囊肿。而且,没有可用的药物或疫苗来治疗或预防SAC囊肿。鉴定在宿主-病原体界面上起作用的相关分子可以大大有助于控制这种疾病。对于其他致病原虫,已经显示糖基磷脂酰肌醇(GPI)是与寄生虫存活和致病性有关的关键分子。这项研究的重点是鉴定参与葡萄球菌GPI生物合成途径的酶和寄生虫GPI锚定蛋白(GPI-AP)的组成。为此,从寄生虫囊肿中提取RNA,并对转录组测序并翻译成氨基酸序列。使用酿酒酵母和弓形虫的特性良好的GPI生物合成酶的序列来挖掘生成的数据库。确定了11种预计参与到葡萄球菌GPI生物合成途径中的酶。另一方面,在数据库中搜索携带N端信号肽和一个包含GPI锚信号的C端跨膜区的蛋白质。鉴定出二十四种GPI锚定的肽,其中九种可能是奥氏链球菌特异性的,而十五种与其他球虫的膜蛋白同源。在后者中,有13个属于SRS域超家族,这是一大组由球虫GPI锚定的蛋白质,介导寄生虫与其宿主的相互作用。系统发育分析表明SRS家族蛋白之间的种内和种间差异很大。需要进行体外和体内实验,以验证葡萄球菌GPI生物合成酶和GPI-APs作为药物靶标和/或疫苗或诊断抗原。其中九个可能是奥氏酵母特异的,而十五个与其他球虫的膜蛋白同源。在后者中,有13个属于SRS域超家族,这是一大组由球虫GPI锚定的蛋白质,介导寄生虫与其宿主的相互作用。系统发育分析表明SRS家族蛋白之间的种内和种间差异很大。需要进行体外和体内实验,以验证葡萄球菌GPI生物合成酶和GPI-APs作为药物靶标和/或疫苗或诊断抗原。其中九个可能是奥氏酵母特异的,而十五个与其他球虫的膜蛋白同源。在后者中,有13个属于SRS域超家族,这是一大组由球虫GPI锚定的蛋白质,介导寄生虫与其宿主的相互作用。系统发育分析表明SRS家族蛋白之间的种内和种间差异很大。需要进行体外和体内实验,以验证葡萄球菌GPI生物合成酶和GPI-APs作为药物靶标和/或疫苗或诊断抗原。系统发育分析表明SRS家族蛋白之间的种内和种间差异很大。需要进行体外和体内实验,以验证葡萄球菌GPI生物合成酶和GPI-APs作为药物靶标和/或疫苗或诊断抗原。系统发育分析表明SRS家族蛋白之间的种内和种间差异很大。需要进行体外和体内实验,以验证葡萄球菌GPI生物合成酶和GPI-APs作为药物靶标和/或疫苗或诊断抗原。
更新日期:2019-12-27
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