Ding Xuan Z, Bhattacharjee Apurba, Nikolich Mikeljon P, Paulsen Ian T, Myers Gary, Seshadri Rekha, L Hoover David
Division of CD&I, Department of Bacterial Diseases, Walter Reed Army Institute of Research, Washington, DC, USA.
Protein Expr Purif. 2005 Mar;40(1):134-41. doi: 10.1016/j.pep.2004.12.017.
Brucella, an aerobic, nonsporeforming, nonmotile Gram-negative coccobacillus, is a NIH/CDC category B bioterror threat agent that causes incapacitating human illness. Medical defense against the bioterror threat posed by Brucella would be strengthened by development of a human vaccine and improved diagnostic tests. Central to advancement of these goals is discovery of bacterial constituents that are immunogenic or antigenic for humans. Outer membrane proteins (OMPs) are particularly attractive for this purpose. In this study, we cloned, expressed, and purified seven predicted OMPs of Brucella suis. The recombinant proteins were fused with 6-His and V5 epitope tags at their C termini to facilitate detection and purification. The B. suis surface genes were PCR synthesized based on their ORF sequences and directly cloned into an entry vector. The recombinant entry constructs were propagated in TOP 10 cells, recombined into a destination vector, pET-DEST42, then transformed into Escherichia coli BL21 cells for IPTG-induced protein expression. The expressed recombinant proteins were confirmed with Western blot analysis using anti-6-His antibody conjugated with alkaline phosphatase. These B. suis OMPs were captured and purified using a HisGrab plate. The purified recombinant proteins were examined for their binding activity with antiserum. Serum derived from a rabbit immunized intramuscularly with dialyzed cell lysate of Brucella rough mutant WRR51. The OMPs were screened using the rabbit antiserum and purified IgG. The results suggested that recombinant B. suis OMPs were successfully cloned, expressed and purified. Some of the expressed OMPs showed high binding activity with immunized rabbit antiserum.
布鲁氏菌是一种需氧、不形成芽孢、无运动性的革兰氏阴性球杆菌,是美国国立卫生研究院/疾病控制与预防中心指定的B类生物恐怖威胁病原体,可导致人类患上使人衰弱的疾病。开发人类疫苗和改进诊断测试将加强针对布鲁氏菌构成的生物恐怖威胁的医学防御。实现这些目标的核心是发现对人类具有免疫原性或抗原性的细菌成分。外膜蛋白(OMPs)为此目的特别具有吸引力。在本研究中,我们克隆、表达并纯化了猪布鲁氏菌的7种预测OMPs。重组蛋白在其C末端与6-His和V5表位标签融合,以促进检测和纯化。猪布鲁氏菌表面基因根据其开放阅读框序列进行PCR合成,并直接克隆到一个入门载体中。重组入门构建体在TOP 10细胞中繁殖,重组到目的载体pET-DEST42中,然后转化到大肠杆菌BL21细胞中进行IPTG诱导的蛋白表达。使用与碱性磷酸酶偶联的抗6-His抗体通过蛋白质印迹分析确认表达的重组蛋白。使用HisGrab平板捕获并纯化这些猪布鲁氏菌OMPs。检查纯化的重组蛋白与抗血清的结合活性。血清取自一只经肌肉注射布鲁氏菌粗糙突变体WRR51的透析细胞裂解物免疫的兔子。使用兔抗血清和纯化的IgG筛选OMPs。结果表明,猪布鲁氏菌重组OMPs成功克隆、表达和纯化。一些表达的OMPs与免疫兔抗血清显示出高结合活性。