Shigella senses environmental cue leucine to promote its colonization and virulence in colon

Shigella is a Gram-negative enteropathogenic bacteria that cause severe bacillary dysentery in humans. Shigella primarily colonizes human large intestine and causes disease via invasion of colon epithelial cells. However, the signal regulatory mechanisms associated with its colonization and pathogenesis in colon remains poorly defined. Here, we report a leucine-mediated regulatory mechanism that promote Shigella colonization and invasion of colon epithelial cells. Shigella in response to leucine, which is highly abundant in the colon, via the leucine-responsive regulator Lrp and the binding of Lrp with leucine induces the expression of a newly identified small RNA SsrV. SsrV then induces the expression of VirF and the downstream invasion-related virulence genes via increasing the protein level of a LysR-type transcription regulator LrhA, therefore enabling Shigella invasion of colon epithelial cells. Shigella lacking either SsrV or lrhA displays impaired invasion ability. Collectively, these findings suggest that Shigella employees the leucine-responsive environmental activation mechanism to establish colonization and pathogenicity.