Shigellapromotes major alteration of gut epithelial physiology and tissue invasion by shutting off host intracellular transport

Nom de la revue
Proceedings of the National Academy of Sciences
Mariana L. Ferrari, Valérie Malardé, Alexandre Grassart, Laura Salavessa, Giulia Nigro, Stéphane Descorps-Declere, John R. Rohde, Pamela Schnupf, Vanessa Masson, Guillaume Arras, Damarys Loew, Philippe J. Sansonetti, Nathalie Sauvonnet
Abstract

Intracellular trafficking pathways in eukaryotic cells are essential to maintain organelle identity and structure, and to regulate cell communication with its environment.
Shigella flexneri
invades and subverts the human colonic epithelium by the injection of virulence factors through a type 3 secretion system (T3SS). In this work, we report the multiple effects of two
S. flexneri
effectors, IpaJ and VirA, which target small GTPases of the Arf and Rab families, consequently inhibiting several intracellular trafficking pathways. IpaJ and VirA induce large-scale impairment of host protein secretion and block the recycling of surface receptors. Moreover, these two effectors decrease clathrin-dependent and -independent endocytosis. Therefore,
S. flexneri
infection induces a global blockage of host cell intracellular transport, affecting the exchange between cells and their external environment. The combined action of these effectors disorganizes the epithelial cell polarity, disturbs epithelial barrier integrity, promotes multiple invasion events, and enhances the pathogen capacity to penetrate into the colonic tissue in vivo.