Proteomics

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Shigella flexneri effectors IpaJ and VirA globally impair host conventional secretion

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.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Shigella Flexneri

SUBMITTER: Guillaume Arras  

LAB HEAD: Damarys Loew

PROVIDER: PXD012291 | Pride | 2019-06-04

REPOSITORIES: Pride

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C4719VM.msf Msf
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Publications

<i>Shigella</i> promotes major alteration of gut epithelial physiology and tissue invasion by shutting off host intracellular transport.

Ferrari Mariana L ML   Malardé Valérie V   Grassart Alexandre A   Salavessa Laura L   Nigro Giulia G   Descorps-Declere Stéphane S   Rohde John R JR   Schnupf Pamela P   Masson Vanessa V   Arras Guillaume G   Loew Damarys D   Sansonetti Philippe J PJ   Sauvonnet Nathalie N  

Proceedings of the National Academy of Sciences of the United States of America 20190617 27

Intracellular trafficking pathways in eukaryotic cells are essential to maintain organelle identity and structure, and to regulate cell communication with its environment. <i>Shigella flexneri</i> 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 <i>S. flexneri</i> effectors, IpaJ and VirA, which target small GTPases of the Arf and Rab families, consequently inhibit  ...[more]

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