Chan Conrad E, Götze Sebastian, Seah Geok T, Seeberger Peter H, Tukvadze Nestan, Wenk Markus R, Hanson Brendon J, MacAry Paul A
1] Department of Microbiology, National University of Singapore [2] Defense Medical and Environmental Research Institute, DSO National Laboratories, Singapore.
1] Max Planck Institute of Colloids and Interfaces, Department of Biomolecular Systems, Germany [2] Department of Chemistry and Biochemistry, Freie Universität Berlin.
Sci Rep. 2015 May 15;5:10281. doi: 10.1038/srep10281.
The current clinical management of TB is complicated by the lack of suitable diagnostic tests that can be employed in infrastructure and resource poor regions. The mannose-capped form of lipoarabinomannan (ManLAM) is unique to the surface envelope of slow-growing, pathogenic mycobacteria such as M.tuberculosis (M.tb) and facilitates passive invasion of mononuclear phagocytes. The detection of this virulence factor in urine, sputum and serum has engendered interest in its employment as a biomarker for M.tb infection. In this study, we utilize a subtractive screening methodology to engineer the first high affinity recombinant antibody (My2F12) with exquisite specificity for the α1-2 mannose linkages enriched in ManLAM from M.tb. My2F12 binds to pathogenic mycobacterial species but not fast growing non-pathogenic species. Testing on matched urine and serum samples from TB patients indicates that My2F12 works in patient cohorts missed by other diagnostic methodologies.
目前结核病的临床管理因缺乏适用于基础设施和资源匮乏地区的诊断测试而变得复杂。甘露糖封端的脂阿拉伯甘露聚糖（ManLAM）形式是诸如结核分枝杆菌（M.tb）等生长缓慢的致病性分枝杆菌表面包膜所特有的，并且有助于单核吞噬细胞的被动侵袭。在尿液、痰液和血清中检测这种毒力因子引发了人们将其用作结核分枝杆菌感染生物标志物的兴趣。在本研究中，我们利用一种消减筛选方法构建了首个对来自结核分枝杆菌的富含α1-2甘露糖连接的ManLAM具有高度特异性的高亲和力重组抗体（My2F12）。My2F12与致病性分枝杆菌物种结合，但不与快速生长的非致病性物种结合。对结核病患者匹配的尿液和血清样本进行检测表明，My2F12在其他诊断方法遗漏的患者群体中有效。
