Babaie Jalal, Miri Mandana, Sadeghiani Ghazaleh, Zare Mehrak, Khalili Ghader, Golkar Majid
Department of Parasitology, Pasteur Institute of Iran, Tehran, Iran.
Avicenna J Med Biotechnol. 2011 Apr;3(2):67-77.
Diagnosis of Toxoplasma gondii (T.gondii) infection is of great medical importance especially for pregnant women and immunosuppressed patients. Numerous studies have shown that the recombinant production of several toxoplasma antigens, including dense granule antigens (GRAs) has a great potential as diagnostic reagents. Previous studies reported expression of amino terminal GRA8 protein in fusion with large tags. In the present study, we produced truncated GRA8 (GRA8), excluded from the signal peptide and C-terminal transmembrane domain, with a short fusion tag in Escherichia coli (E.coli). GRA8 was purified using an optimized single-step Immobilized Metal ion Affinity Chromatography (IMAC). The purity and yield of GRA8 was highest at pH = 9.25. At this pH, 13.6 mg of GRA8 was obtained with the purity of 97.97%. Immunogenicity of the protein was evaluated in Western blot analysis showing the serum sample from a rabbit immunized with GRA8 recognized a single antigen of T.gondii tachyzoite at the expected molecular weight of native GRA8. To diagnosis acute toxoplasma infection in pregnant women, an indirect immunoglobulin M (IgM) enzyme-linked immunosorbent assay (ELISA) was developed using GRA8 resulting in a test specificity and sensitivity of 97.1% and 60.6%, respectively. These results demonstrated that immunogenic GRA8 can be produced in fusion with a short tag and purified near to homogeneity using an optimized IMAC. GRA8-IgM-ELISA was useful for detection of acute toxoplasma infection.
弓形虫(T.gondii)感染的诊断具有重要的医学意义,尤其是对孕妇和免疫抑制患者。众多研究表明,包括致密颗粒抗原(GRAs)在内的多种弓形虫抗原的重组生产作为诊断试剂具有巨大潜力。先前的研究报道了氨基末端GRA8蛋白与大标签融合的表达情况。在本研究中,我们在大肠杆菌(E.coli)中生产了截短的GRA8(GRA8),去除了信号肽和C末端跨膜结构域,并带有一个短融合标签。使用优化的单步固定化金属离子亲和色谱法(IMAC)纯化GRA8。GRA8在pH = 9.25时纯度和产量最高。在此pH值下,获得了13.6 mg纯度为97.97%的GRA8。通过蛋白质印迹分析评估该蛋白的免疫原性,结果显示用GRA8免疫的兔血清样本在天然GRA8预期分子量处识别出单个弓形虫速殖子抗原。为诊断孕妇急性弓形虫感染,利用GRA8开发了一种间接免疫球蛋白M(IgM)酶联免疫吸附测定(ELISA),其检测特异性和敏感性分别为97.1%和60.6%。这些结果表明,具有免疫原性的GRA8可以与短标签融合生产,并使用优化的IMAC纯化至接近均一。GRA8-IgM-ELISA可用于检测急性弓形虫感染。