持留菌是慢性感染复发、细菌耐药以及生物膜形成等临床治疗难题的根本原因。然而，持留菌的形成机制和影响持留菌形成与存活的关键分子尚不明确。我们前期发现大肠埃希菌surA基因缺失菌株（E. coli ΔsurA）持留菌的形成和存活能力明显小于野生菌株E. coli BW25113和其他基因缺失菌株，而且该菌株的持留能力在回补surA基因后恢复到野生菌株的水平，提示surA与持留菌的形成相关。SurA是细菌周质中的伴侣分子，参与外膜蛋白的合成、组装及转运，但其在持留菌形成中的作用尚没有研究报道。本项目拟运用SurA蛋白特异性光交联探针、结合蛋白质组学及基因敲除等技术手段，研究在持留菌形成过程中SurA的靶蛋白、其伴侣作用对靶蛋白的保护效应以及毒素-抗毒素原件效应，从而揭示SurA影响持留菌形成与存活的分子机制。SurA可能会成为抗持留菌药物的靶点，本研究对慢性感染的机制研究和药物设计奠定基础。

Certain infectious diseases caused by pathogenic bacteria are typically chronic in nature. Chronic infections are recalcitrance to treatment with antibiotics in clinical, and consequently follow up with the problems of recurrence infection, drug-resistance and bacterial bio-films. Recently, studies have attributed these clinical problems with persister which is a small fraction of multi-drug tolerance bacteria. But, the mechanism of persister formation, especially the related key molecular, eluded us for a very long time. In our previous studies, we found that E. coli ΔsurA, surA knockout strain, was more susceptible to stresses than the wild type strain E. coli BW25113 and the other gene knockout strains, and its mutant phenotypes could be complemented by surA, which showed that surA was related to persister. SurA is one of periplasmic chaperones, which assists the biogenesis, assembly and transit of outer membrane proteins. However, how does SurA involve in the formation and maintance of persisters is not clear. In this study, we try to use SurA-specific photocrosslinker, in combination with proteomics and gene knockout technologies, to explore the target of SurA，the effect of SurA on persister as chaperone and toxin. SurA might be an effective target for drug against persister, and the results of this research would lay a foundation of the research in chronic infections.