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Designing fusion molecules from antigens of Mycobacterium tuberculosis for detection of multiple antibodies in plasma of TB patients
Tuberculosis ( IF 3.2 ) Pub Date : 2020-09-01 , DOI: 10.1016/j.tube.2020.101981
Mohsina Akhter 1 , Shaista Arif 1 , Aasia Khaliq 2 , Zaib Un Nisa 3 , Imran H Khan 4 , Muhammad Waheed Akhtar 1
Affiliation  

Tuberculosis (TB) is amongst the deadliest diseases worldwide. For effective control of TB a rapid, reliable and sensitive method for its diagnosis is essential. Serodiagnosis detecting multiple antibodies against antigens of Mycobacterium tuberculosis (Mtb) in blood samples could prove beneficial. Based on the epitope position in the molecule, two truncated variants of Rv1984c, i.e., Tn1Rv1984c and Tn2Rv1984c were expressed in Escherichia coli. Screening of the Rv1984c, Tn1Rv1984c and Tn2Rv1984c against 231 sera samples from the culture positive TB patients showed sensitivities of 34.2%, 49.4% and 26.8%, respectively. Another antigen Rv1352 was analyzed for the location of epitopes, which had not been reported before. A fusion molecule consisting of Tn1Rv1984c and Rv1352, expressed in E. coli, showed enhanced sensitivity of 62.8%. Joining another antigen Rv2031c to the N-terminus of Tn1Rv1984c-Rv1352, improved sensitivity to 71.4%. The fusion construct Rv2031c-Tn1Rv1984c-Rv1352 showed comparatively higher sensitivity of 73.4% in the male group as compared to 67% in the female group. Data derived for the secondary structure analysis through Circular Dichroism (CD) spectroscopy and prediction on the basis of molecular modelling was also in agreement. This construct can be a potential base for producing constructs with greater sensitivity through fusion of epitopes from additional Mtb antigens.

中文翻译:

设计来自结核分枝杆菌抗原的融合分子,用于检测结核病患者血浆中的多种抗体

结核病 (TB) 是全世界最致命的疾病之一。为了有效地控制结核病,一种快速、可靠和灵敏的诊断方法是必不可少的。检测血液样本中针对结核分枝杆菌 (Mtb) 抗原的多种抗体的血清诊断可能证明是有益的。基于分子中的表位位置,Rv1984c 的两个截短变体,即 Tn1Rv1984c 和 Tn2Rv1984c 在大肠杆菌中表达。Rv1984c、Tn1Rv1984c 和 Tn2Rv1984c 针对 231 份培养阳性结核病患者的血清样本的筛选显示出分别为 34.2%、49.4% 和 26.8% 的敏感性。对另一种抗原 Rv1352 的表位位置进行了分析,这在以前没有报道过。在大肠杆菌中表达的由 Tn1Rv1984c 和 Rv1352 组成的融合分子显示出 62.8% 的增强灵敏度。将另一个抗原 Rv2031c 连接到 Tn1Rv1984c-Rv1352 的 N 端,将灵敏度提高到 71.4%。融合构建体 Rv2031c-Tn1Rv1984c-Rv1352 在男性组中表现出相对较高的敏感性,为 73.4%,而在女性组中为 67%。通过圆二色性 (CD) 光谱和基于分子建模预测的二级结构分析得出的数据也一致。该构建体可以成为通过融合来自其他 Mtb 抗原的表位来生产具有更高灵敏度的构建体的潜在基础。通过圆二色性 (CD) 光谱和基于分子建模预测的二级结构分析得出的数据也一致。该构建体可以成为通过融合来自其他 Mtb 抗原的表位来生产具有更高灵敏度的构建体的潜在基础。通过圆二色性 (CD) 光谱和基于分子建模预测的二级结构分析得出的数据也一致。该构建体可以成为通过融合来自其他 Mtb 抗原的表位来生产具有更高灵敏度的构建体的潜在基础。
更新日期:2020-09-01
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