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

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 characterized. In this study, we analyzed the interaction of L. interrogans with renal proximal tubule epithelial cells (RPTECs) and found that at 24 h post-infection, L. interrogans remains in close contact with the plasma membrane of the RPTEC by extracellularly adhering or crawling. L. 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), mislocalization 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. This article is protected by copyright. All rights reserved.