LoiA directly represses lon gene expression to activate the expression of Salmonella pathogenicity island-1 genes

Salmonella enterica serovar Typhimurium uses virulence factors encoded by Salmonella pathogenicity island 1 (SPI-1) to invade the intestinal epithelium. The low oxygen-induced transcriptional regulator LoiA is established to be a positive regulator of SPI-1 genes and can also repress the expression of the ATP-dependent Lon protease, a negative regulator of SPI-1 genes. Whether the repression of Ion by LoiA is associated with its regulation of SPI-1 genes, as well as the regulatory mechanism involved, is unknown. In this study, we showed that LoiA directly represses the expression of the Ion gene during invasion by binding to the promoter region of Ion. The activation of S. Typhimurium SPI-1 gene expression by LoiA is associated with its repression of Ion. Moreover, through invasion and mouse infection assays, we found that the repression of Ion by LoiA contributes to S. Typhimurium invasion of intestinal epithelial cells and virulence in mice. However, LoiA does not influence Ion expression during S. Typhimurium growth in macrophages, which may be associated with the low expression level of LoiA in macrophages. Collectively, these findings establish the direct regulation of Ion by LoiA and describe a novel mechanism by which LoiA regulates SPI-1 gene expression. (C) 2019 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.