持留菌能够在遗传物质不变的前提下表现抗生素耐受特性，它与生物被膜形成，以及慢性感染的顽固性密切相关。前期研究表明，胸膜肺炎放线杆菌具有形成持留菌的能力。与野生型相比(p)ppGpp缺失株形成持留菌的能力增强30倍、形成生物膜及对多种抗生素的耐受能力增强，这与之前已报道的(p)ppGpp的缺失使大肠杆菌形成持留菌的能力降低现象截然相反，提示(p)ppGpp调控不同病原菌形成持留菌过程可能存在差异，但具体机制尚未阐明。因此本研究拟通过基因敲除及组学方法从所观察到的差异现象出发，进一步深入分析(p)ppGpp在不同生理状态及压力下对胸膜肺炎放线杆菌形成持留菌的影响，同时对可能参与调控的相关蛋白进行功能验证，并鉴定持留菌形成及恢复过程中参与的新基因及新蛋白。研究结果将为从一个全新的角度解读持留菌的形成机制奠定基础，为揭示细菌慢性感染机制提供有力的参考。

The persisters are cells that have entered a state of low metabolic activity, here referred to as dormant or slow-growing cells under antibiotics treatment, it may contribute significantly to the biofilm formation and the failure to treat chronic infections. In our early research, we found the Actinobacillus pleuropneumoniae can form persister cells. The relA mutant had 30 times higher than the wild-type strain in the ability of forming persister cells. At the same time, the ability of form biofilm and resistant to antibiotics was increased. It was different from the phenomenon that had been reported in the E.coli. So, we speculated that it may have some new mechanism. Thus, we try to explore how the (p)ppGpp influence the persister cells of Actinobacillus pleuropneumoniae under different physiological state and pressure. We prepared to identify the genes that are related to the persister cells formation. And then, we want to discovered some new genes and proteins by the omics method. They may play important role when the wild-type strain entering the persistence and switching back to a growing state. These results would be the foundation for clarify the mechanism of persister cells from a new perspective, and provide powerful reference to solve the problem of bacterial chronic infection.