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.