肠炎沙门氏菌是迄今发现的唯一能够在完整鸡蛋内部生存与增殖的沙门氏菌血清型，它们应对鸡蛋中抑（杀）菌物质的抗逆机制已成为一个重要的科学问题。本项目通过对鸡蛋贮藏过程中和临床儿童病例中肠炎沙门氏菌进行监测、分离鉴定与基因分型，探索二者之间的遗传相关性；将各亚型代表菌株分别采用全蛋液和蛋清组分进行培养与抑菌测试，结合蛋清蛋白质组学研究结果，建立肠炎沙门氏菌的生存与增殖动力学模型和蛋清组分抑菌模型；选取高生长率和不存活的代表菌株、流行克隆株和多重耐药菌株进行全基因组测序和表达芯片分析，并利用自主研发的特异靶点发掘平台筛选出抗逆候选基因和差异位点；结合前人预测的相关基因，采用自主优化的稳定沙门氏菌定点突变系统，实现抗逆基因的突变，以验证其功能；借助蛋白质双向电泳和表达芯片技术，分析抗逆基因间的协同作用，从而在基因组水平上较系统地揭示肠炎沙门氏菌在鸡蛋中生存与增殖的抗逆分子机制。

Salmonella enterica serovar Enteritidis is the only bacterium routinely transmitted to humans through intact chicken eggs, and it means that this bacterium must be able to persist inside chicken eggs. Therefore, the survival and multiplication mechanism of S. Enteritidis against those stress conditions inside chicken eggs has become a key scientific issue. In this study, the monitoring, isolation, identification and genotyping of S. Enteritidis isolates from stored chicken eggs and clinic children patients will be conducted in order to find out the genetic relationship between the two kinds of isolates. The typical subtype isolates will be selected and involved in the cultivation and tests for their abilities of survival and multiplication against effective components of albumen so that the dynamic model of the bacterial survival and multiplication in chicken eggs and the inhibition model of chicken egg albumen to the bacterial isolates will be established. Those typical survival isolates and non-survival isolates (control), epidemic clone strains and multi-drug resistant isolates will be selected for the full-genome sequencing and analysis in gene expression microarray. Possible anti-stress genes (loci) related to the survival and multiplication of S. Enteritidis in chicken egg will be found out by screening with a mining tool for specific gene (loci) in microbial pathogens (SMM-system) developed in our lab. Those possible anti-stress genes (loci) and related genes previously hypothesized will be further characterized and confirmed for their functions by deletion or site-directed mutagenesis. The interaction network among those anti-stress genes (loci) will be developed based on the results of two-dimensional protein electrophoresis and gene expression microarray. Consequently, the anti-stress molecular mechanism for survival and multiplication of S. Enteritidis in chicken eggs will be systematically disclosed at the genomic level.