Miles Sebastián, Navatta Marco, Dematteis Sylvia, Mourglia-Ettlin Gustavo
Cátedra de Inmunología, DEPBIO/IQB. Facultad de Química/Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.
Cátedra de Inmunología, DEPBIO/IQB. Facultad de Química/Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.
Infect Genet Evol. 2017 Oct;54:338-346. doi: 10.1016/j.meegid.2017.07.020. Epub 2017 Jul 17.
Neglected tropical diseases caused by helminth infections currently affect millions of people worldwide. Among them, there are three tapeworm species of outstanding importance: Echinococcus granulosus, E. multilocularis, and Taenia solium, which are responsible for cystic echinococcosis, alveolar echinococcosis, and cysticercosis, respectively. Despite several attempts, there is still a need for an effective and low-cost serological diagnostic test that can be used in endemic countries. In the present work, we described an innovative bioinformatic workflow for a rational prediction of putative peptide candidates for one-step serological diagnosis of any of these infections. First, we predicted the theoretical secretome shared by the three tapeworms starting from their full reported proteomes. Then, through immunoinformatics, we identified proteins within the shared secretome displaying high antigenicity scores and bearing T cell epitopes able to bind most human MHC-II alleles. Secondly, in such proteins, we identified linear B cell epitopes without post-translational modifications, and mapped them on 3D modelled structures to visualize their antibody accessibilities. As a result, we finally suggested two antigenic peptides shared between the secretomes of the three parasite species, which could be further tested for their immunodiagnostic potential.
由蠕虫感染引起的被忽视的热带病目前影响着全球数百万人。其中,有三种绦虫具有突出的重要性:细粒棘球绦虫、多房棘球绦虫和猪带绦虫,它们分别导致囊型包虫病、泡型包虫病和囊尾蚴病。尽管进行了多次尝试,但仍需要一种有效且低成本的血清学诊断测试,可用于流行国家。在本研究中,我们描述了一种创新的生物信息学工作流程,用于合理预测可用于这些感染中任何一种的一步血清学诊断的假定肽候选物。首先,我们从已报道的三种绦虫的完整蛋白质组出发,预测它们共有的理论分泌蛋白组。然后,通过免疫信息学,我们在共享的分泌蛋白组中鉴定出具有高抗原性评分且带有能够结合大多数人类MHC-II等位基因的T细胞表位的蛋白质。其次,在这些蛋白质中,我们鉴定出无翻译后修饰的线性B细胞表位,并将它们映射到三维建模结构上以可视化其抗体可及性。结果,我们最终提出了三种寄生虫物种分泌蛋白组之间共有的两种抗原肽,可进一步测试它们的免疫诊断潜力。