National Key Laboratory of Agricultural Microbiology, Center for Proteomics Research, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.
J Proteome Res. 2010 Dec 3;9(12):6665-77. doi: 10.1021/pr100808n. Epub 2010 Nov 10.
Analysis of the protein-protein interaction network of a pathogen is a powerful approach for dissecting gene function, potential signal transduction, and virulence pathways. This study looks at the construction of a global protein-protein interaction (PPI) network for the human pathogen Mycobacterium tuberculosis H37Rv, based on a high-throughput bacterial two-hybrid method. Almost the entire ORFeome was cloned, and more than 8000 novel interactions were identified. The overall quality of the PPI network was validated through two independent methods, and a high success rate of more than 60% was obtained. The parameters of PPI networks were calculated. The average shortest path length was 4.31. The topological coefficient of the M. tuberculosis B2H network perfectly followed a power law distribution (correlation = 0.999; R-squared = 0.999) and represented the best fit in all currently available PPI networks. A cross-species PPI network comparison revealed 94 conserved subnetworks between M. tuberculosis and several prokaryotic organism PPI networks. The global network was linked to the protein secretion pathway. Two WhiB-like regulators were found to be highly connected proteins in the global network. This is the first systematic noncomputational PPI data for the human pathogen, and it provides a useful resource for studies of infection mechanisms, new signaling pathways, and novel antituberculosis drug development.
分析病原体的蛋白质-蛋白质相互作用网络是剖析基因功能、潜在信号转导和毒力途径的有力方法。本研究基于高通量细菌双杂交方法，构建了人类病原体结核分枝杆菌 H37Rv 的全局蛋白质-蛋白质相互作用（PPI）网络。几乎克隆了整个 ORFeome，并鉴定了超过 8000 个新的相互作用。通过两种独立的方法验证了 PPI 网络的整体质量，成功率超过 60%。计算了 PPI 网络的参数。平均最短路径长度为 4.31。结核分枝杆菌 B2H 网络的拓扑系数完全遵循幂律分布（相关性=0.999；R 平方=0.999），在所有现有 PPI 网络中表现出最佳拟合。种间 PPI 网络比较显示，结核分枝杆菌和几种原核生物 PPI 网络之间存在 94 个保守子网。全局网络与蛋白质分泌途径相关联。在全局网络中发现了两个 WhiB 样调节剂是高度连接的蛋白质。这是人类病原体的第一个系统的非计算性 PPI 数据，为感染机制、新信号通路和新型抗结核药物开发的研究提供了有用的资源。
