Downregulation of Salmonella Virulence Gene Expression During Invasion of Epithelial Cells Treated with Lactococcus lactis subsp. cremoris JFR1 Requires OppA

Invasion ofSalmonellainto host intestinal epithelial cells requires the expression of virulence genes. In this study, cell culture models of human intestinal cells (mucus-producing HT29-MTX cells, absorptive Caco-2 cells, and combined cocultures of the two) were used to determine the effects ofLactococcus lactissubsp.cremoristreatments (exopolysaccharide producing and nonproducing strains) on the virulence gene expression ofSalmonellaTyphimurium and its mutant lacking the oligopeptide permease subunit A (Delta oppA). During the course of epithelial cell (HT29-MTX, Caco-2, and combined) infection bySalmonellaTyphimurium DT104, improved barrier function was reflected by increased transepithelial electrical resistance in cells treated with both strains ofL. lactissubsp.cremoris.In addition, virulence gene expression was downregulated, accompanied with lower numbers of invasive bacteria into epithelial cells in the presence ofL. lactissubsp.cremoristreatments. Similarly, virulence gene expression ofSalmonellawas also suppressed when coincubated with overnight cultures of bothL. lactissubsp.cremorisstrains in the absence of epithelial cells. However, in medium or in the presence of cell cultures,Salmonellalacking the OppA permease function remained virulent. HT29-MTX cells and combined cultures stimulated bySalmonellaTyphimurium DT104 showed significantly lower secretion levels of pro-inflammatory cytokine IL-8 after treatment withL. lactissubsp.cremoriscell suspensions. Contrarily, these responses were not observed during infection withS.Typhimurium Delta oppA.Both the exopolysaccharide producing and nonproducing strains ofL. lactissubsp.cremorisJFR1 exhibited an antivirulence effect againstS.Typhimurium DT104 although no significant difference between the two strains was observed. Our results show that an intact peptide transporter is essential for the suppression ofSalmonellavirulence genes which leads to the protection of the barrier function in the cell culture models studied.