已知葡萄糖可作为信号分子参与细菌的基因表达调控。最近我们研究发现，在伤寒沙门菌中有一双组分调控系统QseBC，能够参与调节细菌的鞭毛及毒力相关基因表达，且环境中加入葡萄糖能显著增强该系统对细菌侵袭力的调节作用。因此我们认为，肠道中食物淀粉水解生成的葡萄糖，可以协助伤寒沙门菌QseBC系统，通过上调侵袭相关基因的表达而提高侵袭力，其相应分子机制有待深入研究。 本项目拟通过基因敲除和DNA芯片比较转录谱分析，结合生物信息学预测，鉴定QseBC的调控元；进而运用定量RT-PCR和凝胶阻滞实验，鉴定QseBC直接调控的靶基因；采用LacZ融合报告基因、引物延伸和DNA酶I足迹实验技术，深入研究QseBC是否并如何直接调控相应基因的转录；最后，将表型和分子实验数据结合起来，认识葡萄糖作用下的QseBC系统是如何通过调控某些关键毒力、鞭毛、生物膜等相关基因的转录，来增强伤寒沙门菌在人体肠道的侵袭力。

Glucose serves as a signaling molecule involved in the regulation of gene expression of bacteria. Recently, we found out that the two-component regulatory system QseBC in Salmonella typhi participates in the regulation of the bacterial flagella and virulence gene expression and glucose can significantly enhances the bacterial invasion of the host. It is our belief therefore that the hydrolysis of intestinal food starch into glucose can activate Salmonella typhi's QseBC system and up-regulate the expression of invasion-related genes. The molecular mechanism for this phenomenon however, remains unknown or is yet to be elucidated. The project intends to apply gene deletion and whole-genome DNA microarray analysis, combined with bioinformatics prediction to identify the QseBC regulon. Quantitative RT-PCR and electrophoretic mobility shift assay will be used to identify genes that are directly regulated by QseBC. LacZ reporter fusion, primer extension and the DNase I footprint assays will reveal the possible mechanism of transcriptional regulation of the target genes by QseBC. Finally, phenotypic observations combined with molecular experimental data will provide significant in-depth knowledge of the mechanism by which glucose can act as a signal for the QseBC system in the transcription of virulence, flagella, and biofilm related genes to enhance the invasiveness of Salmonella typhi of the human gut.