Department of Pathobiology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran.
Animal Health Division, Central Institute for Research on Goats, Makhdoom, Farah, Mathura Uttar Pradesh, India.
PLoS One. 2020 Jun 1;15(6):e0233695. doi: 10.1371/journal.pone.0233695. eCollection 2020.
Johne's disease (JD) is an infectious wasting condition of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP) in domestic livestock of every country that has been investigated. Controlling JD is problematic due to the lack of sensitive, specific, efficient, and cost-effective diagnostic tests. A major challenge in the development of diagnostics like ELISA is the selection of an ideal antigen/(s) that is pathogen-specific and allows sensitive recognition. Therefore, the purpose of this study was to identify and use Mce-truncated protein-based ELISA assay for the diagnosis of MAP infection with high sensitivity and specificity. In silico epitope prediction by epitope mapping throughout the whole length of MAP2191 protein revealed that C-terminal portion of this protein presented potential T- and B-cell epitopes. Therefore, a novel Mce-truncated protein encoded by the selected region of MAP2191 gene was expressed, purified with Ni-NTA gel matrix and confirmed by SDS PAGE and western blot. A profiling ELISA assay was developed to evaluate sera from MAP infected and non-infected ruminant species for antibodies against Mce-truncated protein to infer the immunogenicity of this protein in the host. Using this Mce protein-based ELISA, 251 goats, 53 sheep, 117 buffaloes, and 33 cattle serum samples were screened and 49.4, 51.0, 69.2, and 54.6% animals, respectively, were found positive. Comparing with i-ELISA, the new Mce-based ELISA kit showed a relatively higher specificity but suffered from slightly reduced sensitivity. Mce-based ELISA excluded apparently false positive results of i-ELISA. Mce protein was found to be antigenic and Mce-ELISA test could be employed as a diagnostic test for JD in domestic livestock in view of the a relatively higher specificity and accuracy. The antigenic potential of Mce antigen can also be exploited for the development of a new vaccine for the control of MAP infection.
约翰氏病(JD)是一种传染性消耗性疾病,由每个调查国家的家畜中的分枝杆菌 avium subsp. paratuberculosis(MAP)引起。由于缺乏敏感、特异、高效和具有成本效益的诊断测试,控制 JD 是一个问题。在 ELISA 等诊断方法的开发中,主要挑战是选择具有病原体特异性和允许敏感识别的理想抗原/(s)。因此,本研究的目的是鉴定和使用基于 Mce 截断蛋白的 ELISA 检测法,以具有高灵敏度和特异性来诊断 MAP 感染。通过对 MAP2191 蛋白全长进行表位作图的表位预测,发现该蛋白的 C 端部分存在潜在的 T 细胞和 B 细胞表位。因此,选择 MAP2191 基因的选定区域编码的新型 Mce 截断蛋白被表达、用 Ni-NTA 凝胶基质纯化,并通过 SDS PAGE 和 Western blot 进行确认。开发了一种分析 ELISA 检测法,以评估来自 MAP 感染和未感染反刍动物物种的血清中的抗体,以推断该蛋白在宿主中的免疫原性。使用这种基于 Mce 蛋白的 ELISA,对 251 只山羊、53 只绵羊、117 头水牛和 33 头牛血清样本进行了筛选,分别有 49.4%、51.0%、69.2%和 54.6%的动物呈阳性。与 i-ELISA 相比,新的基于 Mce 的 ELISA 试剂盒显示出相对较高的特异性,但敏感性略有降低。Mce 基于的 ELISA 排除了 i-ELISA 的明显假阳性结果。鉴于相对较高的特异性和准确性,Mce 蛋白被发现是抗原,Mce-ELISA 检测可以作为家畜 JD 的诊断检测方法。Mce 抗原的抗原性也可以被利用来开发控制 MAP 感染的新型疫苗。