Surface layer (
S-layer) proteins are crystalline arrays of proteinaceous subunits present as the outermost component of the cell wall in several Lactobacillus species. The underlying mechanism for how
S-layer proteins inhibit pathogen
infections remains unclear. To gain insights into the mechanism of the antimicrobial activity of Lactobacillus
S-layer proteins, we examined how Lactobacillus
S-layer proteins impact Salmonella Typhimurium-induced apoptosis in vitro in Caco-2 human colon epithelial cells. When Caco-2 cells infected with Salmonella Typhimurium SL1344, we found that apoptosis was mediated by activation of
caspase-3, but not caspase-1. When Salmonella Typhimurium SL1344 and
S-layer proteins were coincubated simultaneously, Caco-2 cell apoptosis was markedly decreased and the cell damage was modified, as evaluated by flow cytometry and microscopy. Detailed analyses showed that the
S-layer proteins inhibited the
caspase-3 activity and activated the
extracellular signal-regulated kinases 1 and 2 (ERK1/2) signaling pathway. Taken together, these findings suggest that Lactobacillus
S-layer proteins protected against Salmonella-induced apoptosis through reduced
caspase-3 activation. In addition, Salmonella-induced apoptotic cell damage was modified by
S-layer proteins through the ERK1/2 signaling pathway. This mechanism may represent a novel approach for antagonizing
Salmonella infection.