Global impact of Salmonella type III secretion effector SteA on host cells

Abstract

Salmonella enterica is a Gram-negative bacterium that causes gastroenteritis, bacteremia and typhoid fever in several animal species including humans. Its virulence is greatly dependent on two type III secretion systems, encoded in pathogenicity islands 1 and 2. These systems translocate proteins called effectors into eukaryotic host cell. Effectors interfere with host signal transduction pathways to allow the internalization of pathogens and their survival and proliferation inside vacuoles. SteA is one of the few Salmonella effectors that are substrates of both type III secretion systems. Here, we used gene arrays and bioinformatics analysis to study the genetic response of human epithelial cells to SteA. We found that constitutive synthesis of SteA in HeLa cells leads to induction of genes related to extracellular matrix organization and regulation of cell proliferation and serine/threonine kinase signaling pathways. SteA also causes repression of genes related to immune processes and regulation of purine nucleotide synthesis and pathway-restricted SMAD protein phosphorylation. In addition, a cell biology approach revealed that epithelial cells expressing steA show altered cell morphology, and decreased cytotoxicity, cell-cell adhesion and migration.

Dynamics and Outcome of Macrophage Interaction Between Salmonella Gallinarum, Salmonella Typhimurium, and Salmonella Dublin and Macrophages From Chicken and Cattle

“…Salmonella has been reported to induce a high level of cell death in both epithelial and phagocytic cells after infections (Santos et al, 2001;Cardenal-Munoz et al, 2014). It is not known whether there are serovar-specific differences in this trait depending on the normal host association of the serovar, and we set out to determine whether cytotoxicity was correlated to the host specificity/host adaptation of the serovar.…”

Salmonellae interactions with host processes

“…In addition, the SPI-1/2 effector SpvC reduces inflammation by inhibiting the production of IL-8 and TNF-α 71 . Another SPI-1/2 effector, SteA elicits changes in the expression of several genes in HeLa cells, including the activation of genes that regulate extracellular matrix organization, cell proliferation and serine/threonine kinase signaling pathways; and the repression of genes involved in regulating immune processes, cell death, adhesion and migration 72 , which suggests that this effector can also modulate inflammation in the host. The effectors SseF, SifA, SspH2, SlrP, PipB2 and SseI can inhibit the migration of dendritic cells 73 , and several of these effectors (SspH2, SlrP, PipB2, SifA, SopD2 and SseFG) also inhibit antigen presentation by dendritic cells and inhibit T-cell proliferation 74 .…”

Expanding the genetic code of Salmonella with non-canonical amino acids

“…As for the target protein for validation, we chose a native Salmonella protein, SteA, a type III secretion effector which contributes to the control of membrane dynamics of Salmonella -containing vacuoles34, globally affecting host cell proliferation, morphology, adhesion and migration35. For minimal perturbation to the protein structure, we selected two tyrosine residues at positions 40 and 155 for Bpa incorporation, individually.…”