Invasion of pancreatic ductal epithelial cells by Enterococcus faecalis is mediated by fibronectin and enterococcal fibronectin-binding protein A
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 th...
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Nature Portfolio
2025-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-025-86531-9 |
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| author | Munefumi Shimosaka Jumpei Kondo Mamika Sonoda Rui Kawaguchi Emika Noda Kaho Nishikori Asuka Ogata Shinji Takamatsu Ken Sasai Hirofumi Akita Hidetoshi Eguchi Yoshihiro Kamada Shigefumi Okamoto Eiji Miyoshi |
| author_facet | Munefumi Shimosaka Jumpei Kondo Mamika Sonoda Rui Kawaguchi Emika Noda Kaho Nishikori Asuka Ogata Shinji Takamatsu Ken Sasai Hirofumi Akita Hidetoshi Eguchi Yoshihiro Kamada Shigefumi Okamoto Eiji Miyoshi |
| author_sort | Munefumi Shimosaka |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-67aab8f8366647a9bc530de5e8a99d82 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-67aab8f8366647a9bc530de5e8a99d822025-01-26T12:30:05ZengNature PortfolioScientific Reports2045-23222025-01-0115111310.1038/s41598-025-86531-9Invasion of pancreatic ductal epithelial cells by Enterococcus faecalis is mediated by fibronectin and enterococcal fibronectin-binding protein AMunefumi Shimosaka0Jumpei Kondo1Mamika Sonoda2Rui Kawaguchi3Emika Noda4Kaho Nishikori5Asuka Ogata6Shinji Takamatsu7Ken Sasai8Hirofumi Akita9Hidetoshi Eguchi10Yoshihiro Kamada11Shigefumi Okamoto12Eiji Miyoshi13Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of MedicineDepartment of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of MedicineDepartment of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of MedicineDepartment of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of MedicineDepartment of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of MedicineDepartment of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of MedicineDepartment of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of MedicineDepartment of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of MedicineDepartment of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of MedicineDepartment of Gastroenterological Surgery, Osaka University Graduate School of MedicineDepartment of Gastroenterological Surgery, Osaka University Graduate School of MedicineDepartment of Advanced Metabolic Hepatology, Osaka University Graduate School of MedicineLaboratory of Medical Microbiology and Microbiome, Department of Clinical Laboratory and Biomedical Sciences, Division of Health Sciences, Osaka University Graduate School of MedicineDepartment of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of MedicineAbstract 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.https://doi.org/10.1038/s41598-025-86531-9 |
| spellingShingle | Munefumi Shimosaka Jumpei Kondo Mamika Sonoda Rui Kawaguchi Emika Noda Kaho Nishikori Asuka Ogata Shinji Takamatsu Ken Sasai Hirofumi Akita Hidetoshi Eguchi Yoshihiro Kamada Shigefumi Okamoto Eiji Miyoshi Invasion of pancreatic ductal epithelial cells by Enterococcus faecalis is mediated by fibronectin and enterococcal fibronectin-binding protein A Scientific Reports |
| title | Invasion of pancreatic ductal epithelial cells by Enterococcus faecalis is mediated by fibronectin and enterococcal fibronectin-binding protein A |
| title_full | Invasion of pancreatic ductal epithelial cells by Enterococcus faecalis is mediated by fibronectin and enterococcal fibronectin-binding protein A |
| title_fullStr | Invasion of pancreatic ductal epithelial cells by Enterococcus faecalis is mediated by fibronectin and enterococcal fibronectin-binding protein A |
| title_full_unstemmed | Invasion of pancreatic ductal epithelial cells by Enterococcus faecalis is mediated by fibronectin and enterococcal fibronectin-binding protein A |
| title_short | Invasion of pancreatic ductal epithelial cells by Enterococcus faecalis is mediated by fibronectin and enterococcal fibronectin-binding protein A |
| title_sort | invasion of pancreatic ductal epithelial cells by enterococcus faecalis is mediated by fibronectin and enterococcal fibronectin binding protein a |
| url | https://doi.org/10.1038/s41598-025-86531-9 |
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