本研究是我们前期首次发现并报道的结核分枝杆菌聚磷酸盐外切酶Rv1026影响分枝杆菌生物膜工作的继续。旨在探索Rv1026调控生物膜形成涉及的靶标以及信号分子等两个关键科学问题。主要研究内容包括：（1）构建分枝杆菌突变菌株；（2）差异发现-研究突变菌株和野生型在生物膜形成过程中，转录组、蛋白质组和代谢物组的差异，生物膜形态和结构差异；（3） 整合转录组、蛋白质组和代谢物组的数据，预测Rv1026调控生物膜形成的可能途径和后续实验验证的重点，（4）三个水平的验证：qPCR在基因转录水平验证，定点突变菌株构建和回补在遗传水平、添加部分化合物在功能水平验证对生物膜形成的影响；（5）建立分子机理模型。上述研究结果可能首先揭示分枝杆菌生物膜形成的调控分子新机理，丰富细菌生物膜形成的分子机理认识，为研发防控生物膜参与的耐药和持留菌措施提供基础。

This proposal aims to elucidate the molecular mechanisms underlying the role of Mycobacterium tuberculosis exopolyphosphatase Rv1026 in the mycobacterial biofilm development, the special emphasis is the underlying target and network, signal molecules involved. The highlighted sections are: (1) construction of the mutants deleted the Rv1026, mutants overexpressed Rv1026; (2) The transcriptome and quantitative proteome dynamics, morphology and structural difference, together with putative signal molecule concentration variation will be depicted and followed; (3) The putative pathway involved in this regulation will be portrayed and crucial nodes will be selected for further validation;(4) quantitative-PCR or small compound entity targetting interested gene or its product will be harnessed to validate their effect upon mycobacterial biofilm formation; (5) a model representing above findings will be formulated. The answer to above scientific questions will shed new lights on the regulation of mycobacterial biofilm and other bacterial biofilm, serving as a basis to discover more targets, especially biofilm related ones, to tackle the drug resistant or persistent bacterial infection.