A post-transcriptional link between Salmonella metabolism and virulence

本项目旨在探索一种新型的糖代谢和毒力因子表达的转录后整合模式病原体，沙门氏菌肠血清型鼠伤寒沙门氏菌。我们将研究双功能SgrS RNA，该RNA最近被描述为非致病性大肠杆菌中编码主要葡萄糖转运蛋白IICBGlc的ptsG mRNA的磷酸糖应激诱导的阻遏物。杆菌我们在沙门氏菌中的初步工作不仅证实了ptsG的调控，而且发现了SgrS的新靶点。这些包括抑制sopD编码水平获得的蛋白质，该蛋白质通过沙门氏菌3型分泌装置易位到宿主细胞中，以及激活yigL，其基因产物是对葡萄糖-6-磷酸具有高亲和力的推定水解酶。鉴于葡萄糖是细胞内沙门氏菌的主要碳源，我们推测SgrS可能构成一个新的转录后节点，有助于协调代谢和毒力因子的表达。利用SPP 1316的专业知识，我们将建立相关的生长条件和细胞类型，研究SgrS在感染过程中的活性。转录组学和代谢分析将用于确定SgrS介导的调节其靶基因的碳通量和利用的生理后果，以重建SgrS入侵后和细胞内复制期间的遗传控制网络。

This project aims to explore a novel type of post-transcriptional integration of sugar metabolism and virulence factor expression in the model pathogen, Salmonella enterica serovar Typhimurium. We will investigate the bifunctional SgrS RNA which has recently been described as a phosphosugar stress-induced repressor of ptsG mRNA encoding the primary glucose transporter IICBGlc in nonpathogenic E. coli. Our preliminary work in Salmonella has not only confirmed the regulation of ptsG but also discovered new targets of SgrS. These include a repression of sopD encoding a horizontally acquired protein that is translocated into host cells by the Salmonella type 3 secretion apparatus, and an activation of yigL whose gene product is a putative hydrolase with high affinity for glucose-6-phosphate. Given that glucose is the major carbon source of intracellular Salmonella, we speculate that SgrS might constitute a novel post-transcriptional node that helps coordinate metabolism and virulence factor expression. Exploiting the expertise available in SPP1316, we will establish relevant growth conditions and cell types study the activity of SgrS during the course of infection. Transcriptomics and metabolic profiling will be used to determine the physiological consequences of SgrS-mediated regulation of its target genes for carbon flux and utilization to reconstruct a network of genetic control by SgrS upon invasion and during intracellular replication.