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dc.contributor.authorPearson, J.S.
dc.contributor.authorGiogha, C.
dc.contributor.authorOng, Sze Ying
dc.contributor.authorKennedy, C.L.
dc.contributor.authorKelly, Michelle
dc.contributor.authorRobinson, K.S.
dc.contributor.authorLung, Tania Wong Fok
dc.contributor.authorMansell, Ashley
dc.contributor.authorRiedmaier, P.
dc.contributor.authorOates, C.V.L.
dc.contributor.authorZaid, Ali
dc.contributor.authorMuhlen, S.
dc.contributor.authorCrepin, V.F.
dc.contributor.authorMarches, O.
dc.contributor.authorAng, Ching-Seng
dc.contributor.authorWilliamson, N.A.
dc.contributor.authorO'Reilly, L.A.
dc.contributor.authorBankovacki, A.
dc.contributor.authorNachbur, U.
dc.contributor.authorInfusini, G.
dc.contributor.authorWebb, A.I.
dc.contributor.authorSilke, J.
dc.contributor.authorStrasser, Andreas
dc.contributor.authorFrankel, G.
dc.contributor.authorHartland, E.L.
dc.date.accessioned2018-04-27T04:02:03Z
dc.date.available2018-04-27T04:02:03Z
dc.date.issued2013
dc.identifier.issn0028-0836en_US
dc.identifier.doi10.1038/nature12524en_US
dc.identifier.urihttp://hdl.handle.net/10072/173031
dc.description.abstractSuccessful infection by enteric bacterial pathogens depends on the ability of the bacteria to colonize the gut, replicate in host tissues and disseminate to other hosts. Pathogens such as Salmonella, Shigella and enteropathogenic and enterohaemorrhagic (EPEC and EHEC, respectively) Escherichia coli use a type III secretion system (T3SS) to deliver virulence effector proteins into host cells during infection that promote colonization and interfere with antimicrobial host responses1,2,3. Here we report that the T3SS effector NleB1 from EPEC binds to host cell death-domain-containing proteins and thereby inhibits death receptor signalling. Protein interaction studies identified FADD, TRADD and RIPK1 as binding partners of NleB1. NleB1 expressed ectopically or injected by the bacterial T3SS prevented Fas ligand or TNF-induced formation of the canonical death-inducing signalling complex (DISC) and proteolytic activation of caspase-8, an essential step in death-receptor-induced apoptosis. This inhibition depended on the N-acetylglucosamine transferase activity of NleB1, which specifically modified Arg 117 in the death domain of FADD. The importance of the death receptor apoptotic pathway to host defence was demonstrated using mice deficient in the FAS signalling pathway, which showed delayed clearance of the EPEC-like mouse pathogen Citrobacter rodentium and reversion to virulence of an nleB mutant. The activity of NleB suggests that EPEC and other attaching and effacing pathogens antagonize death-receptor-induced apoptosis of infected cells, thereby blocking a major antimicrobial host response.en_US
dc.description.peerreviewedYesen_US
dc.languageEnglishen_US
dc.publisherNature Publishingen_US
dc.relation.ispartofpagefrom247en_US
dc.relation.ispartofpageto251en_US
dc.relation.ispartofjournalNatureen_US
dc.relation.ispartofvolume501en_US
dc.subject.fieldofresearchImmunology not elsewhere classifieden_US
dc.subject.fieldofresearchcode110799en_US
dc.titleA type III effector antagonizes death receptor signalling during bacterial gut infectionen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.rights.copyright© 2013 Nature Publishing Group. This is the author-manuscript version of this paper. Reproduced in accordance with the copyright policy of the publisher. Please refer to the journal website for access to the definitive, published version.en_US
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