The putative AraC-type transcriptional regulator STM1082 facilitates Salmonella pathogenicity through modulation of intestinal invasion and intracellular replication

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 identified STM1082, a putative AraC-type transcriptional regulator, as a new virulence activator in Salmonella. The expression of the STM1082 gene is up-regulated when Salmonella invades HeLa epithelial cells and replicates within RAW264.7 macrophages. Mutation of STM1082 impaired the ability of Salmonella to invade HeLa cells and replicate in RAW264.7 cells, and reduced its colonization in the mouse intestine, liver, and spleen. These results suggest that STM1082 facilitates Salmonella pathogenicity by promoting both its intestinal and systemic infections. Moreover, under intestinal-mimicking conditions, STM1082 increased the expression of genes related to 1,2-propanediol and ethanolamine metabolism, which are linked to Salmonella‘s intestinal survival. Under macrophage-mimicking conditions, it upregulated genes involved in purine biosynthesis, associated with Salmonella‘s systemic virulence. Together, these findings highlight the significant role of STM1082 in modulating the pathogenic mechanisms of Salmonella.