Disassembly of the apical junctional complex during the transmigration of Leptospira interrogans across polarized renal proximal tubule epithelial cells. 2021

Isabel Sebastián, and Nobuhiko Okura, and Bruno M Humbel, and Jun Xu, and Idam Hermawan, and Chiaki Matsuura, and Malgorzata Hall, and Chitoshi Takayama, and Tetsu Yamashiro, and Shuichi Nakamura, and Claudia Toma
Department of Bacteriology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.

Bacterial pathogens have evolved multiple strategies to disassemble epithelial cell apical junctional complexes (AJCs) and infect epithelial cells. Leptospirosis is a widespread zoonotic infection, mainly caused by Leptospira interrogans, and its dissemination across host cell barriers is essential for its pathogenesis. However, the mechanism of bacterial dissemination across epithelial cell barriers remains poorly characterised. In this study, we analysed the interaction of L. interrogans with renal proximal tubule epithelial cells (RPTECs) and found that at 24 hr post-infection, L. interrogans remain in close contact with the plasma membrane of the RPTEC by extracellularly adhering or crawling. Leptospira interrogans cleaved E-cadherin and induced its endocytosis with release of the soluble N-terminal fragment into the extracellular medium. Concomitantly, a gradual decrease in transepithelial electrical resistance (TEER), mislocalisation of AJC proteins (occludin, claudin-10, ZO-1, and cingulin) and cytoskeletal rearrangement were observed. Inhibition of clathrin-mediated E-cadherin endocytosis prevented the decrease in TEER. We showed that disassembly of AJCs in epithelial cells and transmigration of bacteria through the paracellular route are important for the dissemination of L. interrogans in the host.

UI MeSH Term Description Entries
D007365 Intercellular Junctions Direct contact of a cell with a neighboring cell. Most such junctions are too small to be resolved by light microscopy, but they can be visualized by conventional or freeze-fracture electron microscopy, both of which show that the interacting CELL MEMBRANE and often the underlying CYTOPLASM and the intervening EXTRACELLULAR SPACE are highly specialized in these regions. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p792) Cell Junctions,Cell Junction,Intercellular Junction,Junction, Cell,Junction, Intercellular,Junctions, Cell,Junctions, Intercellular
D007921 Leptospira interrogans A genus of question mark-shaped bacteria spirochetes which is found in fresh water that is contaminated by animal urine. It causes LEPTOSPIROSIS. Leptospira icteroides,Spirochaeta icterogenes,Spirochaeta icterohaemorrhagiae,Spirochaeta interrogans,Spirochaeta nodosa
D007922 Leptospirosis Infections with bacteria of the genus LEPTOSPIRA. Cane-Cutter Fever,Canicola Fever,Leptospira Canicola Infection,Leptospira Infection,Leptospirosis Canicola,Mud Fever,Rice-Field Fever,Stuttgart Disease,Swineherd's Disease,Cane Cutter Fever,Fever, Canicola,Fever, Mud,Fever, Rice-Field,Fevers, Cane-Cutter,Infection, Leptospira,Infection, Leptospira Canicola,Infections, Leptospira,Infections, Leptospira Canicola,Leptospira Canicola Infections,Leptospira Infections,Leptospiroses,Leptospirosis Canicolas,Rice Field Fever,Swineherd's Diseases
D004705 Endocytosis Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis. Endocytoses
D004847 Epithelial Cells Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells. Adenomatous Epithelial Cells,Columnar Glandular Epithelial Cells,Cuboidal Glandular Epithelial Cells,Glandular Epithelial Cells,Squamous Cells,Squamous Epithelial Cells,Transitional Epithelial Cells,Adenomatous Epithelial Cell,Cell, Adenomatous Epithelial,Cell, Epithelial,Cell, Glandular Epithelial,Cell, Squamous,Cell, Squamous Epithelial,Cell, Transitional Epithelial,Cells, Adenomatous Epithelial,Cells, Epithelial,Cells, Glandular Epithelial,Cells, Squamous,Cells, Squamous Epithelial,Cells, Transitional Epithelial,Epithelial Cell,Epithelial Cell, Adenomatous,Epithelial Cell, Glandular,Epithelial Cell, Squamous,Epithelial Cell, Transitional,Epithelial Cells, Adenomatous,Epithelial Cells, Glandular,Epithelial Cells, Squamous,Epithelial Cells, Transitional,Glandular Epithelial Cell,Squamous Cell,Squamous Epithelial Cell,Transitional Epithelial Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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