Universidad Abierta Interamericana (UAI), Centro de Altos Estudios en Ciencias Humanas y de la Salud (CAECIHS), Buenos Aires, Argentina.
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
Front Cell Infect Microbiol. 2022 Jun 13;12:901994. doi: 10.3389/fcimb.2022.901994. eCollection 2022.
Cystic echinococcosis (CE) is a zoonotic disease worldwide distributed, caused by the cestode sensu lato (), with an incidence rate of 50/100,000 person/year and a high prevalence in humans of 5-10%. Serology has variable sensitivity and specificity and low predictive values. Antigens used are from the hydatid fluid and recombinant antigens have not demonstrated superiority over hydatid fluid. A cell line called EGPE was obtained from sensu lato G1 strain from bovine liver. Serum from CE patients recognizes protein extracts from EGPE cells with higher sensitivity than protein extracts from hydatid fluid. In the present study, EGPE cell protein extracts and supernatants from cell colonies were eluted from a protein G affinity column performed with sera from 11 CE patients. LC-MS/MS proteomic analysis of the eluted proteins identified four histones: one histone H4 in the cell extract and supernatant, one histone H2A only in the cell extract, and two histones H2A only in the supernatant. This differential distribution of histones could reflect different parasite viability stages regarding their role in gene transcription and silencing and could interact with host cells. Bioinformatics tools characterized the linear and conformational epitopes involved in antibody recognition. The three-dimensional structure of each histone was obtained by molecular modeling and validated by molecular dynamics simulation and PCR confirmed the presence of the epitopes in the parasite genome. The three histones H2A were very different and had a less conserved sequence than the histone H4. Comparison of the histones of with those of other organisms showed exclusive regions for . Since histones play a role in the host-parasite relationship they could be good candidates to improve the predictive value of serology in CE.
包虫病(CE)是一种全球性分布的人畜共患疾病,由广义绦虫()引起,发病率为 50/100,000 人/年,人类患病率高达 5-10%。血清学具有可变的敏感性和特异性,预测值较低。使用的抗原来自包虫液,重组抗原并未显示优于包虫液的优势。从牛肝中获得的广义绦虫 G1 株获得了一种称为 EGPE 的细胞系。CE 患者的血清可识别 EGPE 细胞蛋白提取物的敏感性高于包虫液蛋白提取物。在本研究中,从 11 例 CE 患者的血清中进行了蛋白 G 亲和柱洗脱,对 EGPE 细胞蛋白提取物和细胞集落上清液进行了 LC-MS/MS 蛋白质组分析。洗脱蛋白的分析鉴定出四种组蛋白:细胞提取物和上清液中的一种组蛋白 H4,仅在细胞提取物中的一种组蛋白 H2A,以及仅在上清液中的两种组蛋白 H2A。组蛋白的这种差异分布可能反映了寄生虫在基因转录和沉默方面的不同存活阶段,并且可以与宿主细胞相互作用。生物信息学工具描述了参与抗体识别的线性和构象表位。通过分子建模获得了每个组蛋白的三维结构,并通过分子动力学模拟进行了验证,PCR 证实了这些表位存在于寄生虫基因组中。三种组蛋白 H2A 差异很大,与组蛋白 H4 的序列保守性较低。与其他生物体的组蛋白进行比较显示了 的特有区域。由于组蛋白在宿主-寄生虫关系中发挥作用,因此它们可能是提高 CE 血清学预测值的良好候选物。