000070593 001__ 70593
000070593 005__ 20190709135618.0
000070593 0247_ $$2doi$$a10.1074/jbc.M117.790675
000070593 0248_ $$2sideral$$a104786
000070593 037__ $$aART-2017-104786
000070593 041__ $$aeng
000070593 100__ $$aEl Qaidi, S.
000070593 245__ $$aNleB/SseK effectors from Citrobacter rodentium, Escherichia coli, and Salmonella enterica display distinct differences in host substrate specificity
000070593 260__ $$c2017
000070593 5060_ $$aAccess copy available to the general public$$fUnrestricted
000070593 5203_ $$aMany Gram-negative bacterial pathogens use a syringe-like apparatus called a type III secretion system to inject virulence factors into host cells. Some of these effectors are enzymes that modify host proteins to subvert their normal functions. NleB is a glycosyltransferase that modifies host proteins with N-acetyl-D-glucosamine to inhibit antibacterial and inflammatory host responses. NleB is conserved among the attaching/effacing pathogens enterohemorrhagic Escherichia coli (EHEC), enteropathogenic E. coli (EPEC), and Citrobacter rodentium. Moreover, Salmonella enterica strains encode up to three NleB orthologs named SseK1, SseK2, and SseK3. However, there are conflicting reports regarding the activities and host protein targets among the NleB/SseK orthologs. Therefore, here we performed in vitro glycosylation assays and cell culture experiments to compare the activities and substrate specificities of these effectors. SseK1, SseK3, EHEC NleB1, EPEC NleB1, and C. rodentium NleB blocked TNF-mediated NF-B pathway activation, whereas SseK2 and NleB2 did not. C. rodentium NleB, EHEC NleB1, and SseK1 glycosylated host GAPDH. C. rodentium NleB, EHEC NleB1, EPEC NleB1, and SseK2 glycosylated the FADD (Fas-associated death domain protein). SseK3 and NleB2 were not active against either substrate. We also found that EHEC NleB1 glycosylated two GAPDH arginine residues, Arg197 and Arg200, and that these two residues were essential for GAPDH-mediated activation of TNF receptor-associated factor 2 ubiquitination. These results provide evidence that members of this highly conserved family of bacterial virulence effectors target different host protein substrates and exhibit distinct cellular modes of action to suppress host responses.
000070593 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/
000070593 590__ $$a4.01$$b2017
000070593 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b75 / 292 = 0.257$$c2017$$dQ2$$eT1
000070593 592__ $$a2.672$$b2017
000070593 593__ $$aBiochemistry$$c2017$$dQ1
000070593 593__ $$aMolecular Biology$$c2017$$dQ1
000070593 593__ $$aCell Biology$$c2017$$dQ1
000070593 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000070593 700__ $$aChen, K.
000070593 700__ $$aHalim, A.
000070593 700__ $$aSiukstaite, L.
000070593 700__ $$aRueter, C.
000070593 700__ $$0(orcid)0000-0002-3122-9401$$aHurtado-Guerrero, R.$$uUniversidad de Zaragoza
000070593 700__ $$aClausen, H.
000070593 700__ $$aHardwidge, P.R.
000070593 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000070593 773__ $$g292, 27 (2017), 11423-11430$$pJ. biol. chem.$$tJournal of Biological Chemistry$$x0021-9258
000070593 8564_ $$s473240$$uhttps://zaguan.unizar.es/record/70593/files/texto_completo.pdf$$yVersión publicada
000070593 8564_ $$s149560$$uhttps://zaguan.unizar.es/record/70593/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000070593 909CO $$ooai:zaguan.unizar.es:70593$$particulos$$pdriver
000070593 951__ $$a2019-07-09-12:26:24
000070593 980__ $$aARTICLE