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中国科学家构建首张结核分枝杆菌全蛋白质组芯片结核病是古老又新发的传染病,死亡人数为各类传染病之首。结核病的防控目前面临三大难题:一是疫苗使用近百年,保护率和保护期受到质疑;二是现有的药物使用历史超过半世纪,耐药性日趋严重;三是诊断缺乏标识物,检出率低。2014年12月11日,中科院生物物理所、武汉病毒所和上海交大、广东省结核病防治中心、广东体必康公司等机构的学者和临床专家近日在Cell Reports杂志上在线发表了题为"Mycobacterium tuberculosis Proteome Microarray for Global Studies of Protein Function and Immunogenicity"的研究成果。该蛋白质组芯含4262个结核分枝杆菌基因组阅读框架编码产物,覆盖其基因组编码蛋白质的95%,可用于全局性蛋白-蛋白相互作用分析,以研究人免疫细胞-结核杆菌的互作机制;小分子与蛋白相互作用分析,以进行药物靶标的全局性发现;高通量血清分析,以系统性地进行结核病诊断生物标识物的发现。本文基于该芯片分析了蛋白激酶PknG及小分子C-di-GMP的相互作用蛋白,发现结核杆菌的鼠李糖通路可能会受到以上两个分子的同步调控,并且还利用芯片发现了14个可以区分结核病人和治愈者的标识蛋白。结核分枝杆菌蛋白质组芯片为结核病研究打开新的窗口,可以系统性发现新的免疫原和新的标志物,从而发展新型高效疫苗、新药和检测技术,是结核病基础研究强有力的新方法学平台。该项研究历时五年完成。得到国家"十二五"传染病重大专项、中科院重点项目、国家863项目以及国家自然科学基金项目等的支持。(生物谷Bioon.com) 参考文献 Mycobacterium Tuberculosis Proteome Microarray for Global Studies of Protein Function and Immunogenicity DOI: http://dx.doi.org/10.1016/j.celrep.2014.11.023 Poor understanding of the basic biology of Mycobacterium tuberculosis (MTB), the etiological agent of tuberculosis, hampers development of much-needed drugs, vaccines, and diagnostic tests. Better experimental tools are needed to expedite investigations of this pathogen at the systems level. Here, we present a functional MTB proteome microarray covering most of the proteome and an ORFome library. We demonstrate the broad applicability of the microarray by investigating global protein-protein interactions, small-molecule-protein binding, and serum biomarker discovery, identifying 59 PknG-interacting proteins, 30 bis-(3′-5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) binding proteins, and 14 MTB proteins that together differentiate between tuberculosis (TB) patients with active disease and recovered individuals. Results suggest that the MTB rhamnose pathway is likely regulated by both the serine/threonine kinase PknG and c-di-GMP. This resource has the potential to generate a greater understanding of key biological processes in the pathogenesis of tuberculosis, possibly leading to more effective therapies for the treatment of this ancient disease. |