A Study on the Pathogenic Mechanism of Salmonella

Salmonella is a food-borne zoonotic pathogen that causes human gastroenteritis and potentially fatal systemic infections. The invasion of intestinal epithelial cells and the survival and replication within host macrophages are essential for the intestinal and systemic infections caused by Salmonella, respectively. To precisely regulate the expression of virulence-related genes, Salmonella relies on a series of regulatory proteins. In this study, we have identified STM1082, a putative AraC-type transcriptional regulator, as a novel virulence activator in Salmonella. We found that the expression of the STM1082 gene is significantly up-regulated when Salmonella invades HeLa epithelial cells and replicates within RAW264.7 macrophages. Mutation of STM1082 impairs the ability of Salmonella to invade HeLa cells and replicate in RAW264.7 cells, and also decreased the colonization of Salmonella in the mouse intestine and systemic sites (liver and spleen). These results suggest that STM1082 facilitates Salmonella pathogenicity by promoting both its intestinal and systemic infections. Additionally, we found that under intestinal-mimicking conditions, STM1082 upregulates the expression of genes involved in 1, 2-propanediol and ethanolamine metabolism, which have been reported to be associated with the intestinal survival of Salmonella. Under macrophage-mimicking conditions, it upregulates the expression of genes involved in purine biosynthesis, which have been reported to be associated with the systemic virulence of Salmonella. Together, these findings highlight the significant role of STM1082 in modulating the pathogenic mechanisms of Salmonella.

沙门氏菌（Salmonella）是一种食源性人兽共患病原菌，可引发人类胃肠炎以及潜在致命性全身感染。沙门氏菌侵袭肠上皮细胞，以及在宿主巨噬细胞内存活并增殖，分别是其引发肠道感染和全身感染的关键致病环节。为精准调控毒力相关基因的表达，沙门氏菌依赖一系列调控蛋白。本研究中，我们将假定的AraC型转录调节因子（AraC-type transcriptional regulator）STM1082鉴定为沙门氏菌中一种新型毒力激活因子。我们发现，当沙门氏菌侵袭海拉（HeLa）上皮细胞并在RAW264.7巨噬细胞内增殖时，STM1082基因的表达显著上调。STM1082基因的突变会削弱沙门氏菌侵袭HeLa细胞以及在RAW264.7细胞内增殖的能力，同时还会降低沙门氏菌在小鼠肠道及全身定植部位（肝脏与脾脏）的载菌量。上述结果表明，STM1082可通过促进沙门氏菌的肠道感染与全身感染，增强其致病能力。此外，我们发现，在模拟肠道环境的条件下，STM1082可上调参与1,2-丙二醇与乙醇胺代谢的基因的表达，这类基因此前已有报道与沙门氏菌的肠道存活相关。在模拟巨噬细胞环境的条件下，STM1082可上调参与嘌呤生物合成的基因的表达，这类基因此前已有报道与沙门氏菌的全身毒力相关。综上，这些研究结果凸显了STM1082在调控沙门氏菌致病机制中的重要作用。