Spermidine facilitates the adhesion and subsequent invasion of Salmonella Typhimurium into epithelial cells via the regulation of surface adhesive structures and the SPI-1

Abstract

Polyamines are poly-cationic molecules ubiquitously present in all organisms. Salmonella synthesizes and also harbors specialized ABC transporters to uptake polyamines. Polyamines assist in pathogenesis and stress resistance in Salmonella; however, the mechanism remains elusive. The virulence trait of Salmonella depends on the injection of effector proteins into the host cell and modulation of host machinery and employs an array of arsenals to colonize in the host niche successfully. However, prior to this, Salmonella utilizes multiple surface structures to attach and adhere to the surface of the target cells. Our study solves the enigma of how polyamine spermidine assists in the pathogenesis of Salmonella. We show that spermidine mediates the initial attachment and adhesion of Salmonella Typhimurium to Caco-2 cells, facilitating its invasion. In-vivo studies showed that polyamines are required for invasion into the murine Peyers patches. Polyamines have previously been shown to regulate the transcription of multiple genes in both eukaryotes and prokaryotes. We show that spermidine controls the RNA expression of the two-component system, BarA/SirA, that further regulates multiple fimbrial and non-fimbrial adhesins in Salmonella. Flagella is also a vital surface structure aiding in motility and attachment to surfaces of host cells and gall stones. Spermidine regulated the expression of flagellin genes by enhancing the translation of s28, which features an unusual start codon and a poor Shine-Dalgarno sequence. Besides regulating the formation of the adhesive structures, spermidine tunes the expression of the Salmonella pathogenicity island-1 encoded genes. Thus, our study unravels a novel mechanism by which spermidine aids in the adhesion and the subsequent invasion of Salmonella into host cells.