Invasion of pancreatic ductal epithelial cells by Enterococcus faecalis is mediated by fibronectin and enterococcal fibronectin-binding protein A

Abstract

Abstract The poor prognosis of pancreatic cancer is often attributed to difficulties of early detection due to a lack of appropriate risk factors. Previously, we demonstrated the presence of Enterococcus faecalis (E. faecalis) in pancreatic juice and tissues obtained from patients with cancers of the duodeno-pancreato-biliary region, suggesting the possible involvement of this bacterial species in chronic and malignant pancreatic diseases. However, it remains unclear if and how E. faecalis can infect pancreatic ductal cells. In this study, we used immortalized normal human pancreatic ductal epithelial cells (iPDECs) and pancreatic ductal cancer cell lines to demonstrate that E. faecalis adheres to and invades pancreatic ductal lineage epithelial cells. Inhibitors of micropinocytosis or clathrin- or caveolae-mediated endocytosis suppressed iPDEC invasion by E. faecalis. Mechanistically, bacterial expression of enterococcal fibronectin-binding protein A (EfbA) was correlated with adhesive potential of E. faecalis strains. Knockout of fibronectin 1, a binding partner of EfbA, in iPDECs resulted in suppressed E. faecalis adhesion and invasion, suggesting the importance of the EfbA-fibronectin axis in infection of pancreatic ductal epithelial lineage cells. Overall, these results suggest that E. faecalis can colonize pancreatic tissue by infecting iPDECs, at least in part, via the expression of the cell adhesion factor EfbA.