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Escherichia coli Producing CNF1 Toxin Hijacks Tollip to Trigger Rac1‐Dependent Cell Invasion
Author(s) -
Visvikis Orane,
Boyer Laurent,
Torrino Stéphanie,
Doye Anne,
Lemonnier Marc,
Lorès Patrick,
Rolando Monica,
Flatau Gilles,
Mettouchi Amel,
Bouvard Daniel,
Veiga Esteban,
Gacon Gérard,
Cossart Pascale,
Lemichez Emmanuel
Publication year - 2011
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/j.1600-0854.2011.01174.x
Subject(s) - biology , rac1 , microbiology and biotechnology , internalization , clathrin , gene knockdown , rac gtp binding proteins , endocytosis , cell , cell culture , signal transduction , genetics
Rho GTPases, which are master regulators of both the actin cytoskeleton and membrane trafficking, are often hijacked by pathogens to enable their invasion of host cells. Here we report that the cytotoxic necrotizing factor‐1 (CNF1) toxin of uropathogenic Escherichia coli (UPEC) promotes Rac1‐dependent entry of bacteria into host cells. Our screen for proteins involved in Rac1‐dependent UPEC entry identifies the Toll‐interacting protein (Tollip) as a new interacting protein of Rac1 and its ubiquitinated forms. We show that knockdown of Tollip reduces CNF1‐induced Rac1‐dependent UPEC entry. Tollip depletion also reduces the Rac1‐dependent entry of Listeria monocytogenes expressing InlB invasion protein. Moreover, knockdown of Tollip, Tom1 and clathrin, decreases CNF1 and Rac1‐dependent internalization of UPEC. Finally, we show that Tollip, Tom1 and clathrin associate with Rac1 and localize at the site of bacterial entry. Collectively, these findings reveal a new link between Rac1 and Tollip, Tom1 and clathrin membrane trafficking components hijacked by pathogenic bacteria to allow their efficient invasion of host cells.