title: Escherichia coli producing CNF1 toxin hijacks Tollip to trigger Rac1-dependent cell invasion.
abstract: 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.
authors.affiliation: INSERM, U895, Centre Méditerranéen de Médecine Moléculaire, C3M, Toxines Microbiennes dans la relation hôte pathogènes, Nice, F-06204 Cedex 3, France.
authors.forename: Orane
authors.initials: O
authors.lastname: Visvikis
authors.forename: Laurent
authors.initials: L
authors.lastname: Boyer
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Torrino
authors.forename: Anne
authors.initials: A
authors.lastname: Doye
authors.forename: Marc
authors.initials: M
authors.lastname: Lemonnier
authors.forename: Patrick
authors.initials: P
authors.lastname: Lorès
authors.forename: Monica
authors.initials: M
authors.lastname: Rolando
authors.forename: Gilles
authors.initials: G
authors.lastname: Flatau
authors.forename: Amel
authors.initials: A
authors.lastname: Mettouchi
authors.forename: Daniel
authors.initials: D
authors.lastname: Bouvard
authors.forename: Esteban
authors.initials: E
authors.lastname: Veiga
authors.forename: Gérard
authors.initials: G
authors.lastname: Gacon
authors.forename: Pascale
authors.initials: P
authors.lastname: Cossart
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Lemichez
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000378:metabolism*; D001427:Bacterial Toxins / Q000378:metabolism*; D002460:Cell Line; D004705:Endocytosis / Q000502:physiology; D029968:Escherichia coli Proteins / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D011506:Proteins / Q000378:metabolism; D056689:Uropathogenic Escherichia coli / Q000166:cytology / Q000378:metabolism* / Q000472:pathogenicity*; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D001427:Bacterial Toxins; D029968:Escherichia coli Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C410602:TOLLIP protein, human; C120296:TOM1 protein, human; C060296:cytotoxic necrotizing factor type 1; D020830:rac1 GTP-Binding Protein