NleB, a bacterial effector with glycosyltransferase activity targets GADPH function to inhibit NF-κB activation

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dc.contributor.author Gao, Xiaofei
dc.contributor.author Wang, Xiaogang
dc.contributor.author Pham, Thanh H.
dc.contributor.author Feuerbacher, Leigh Ann
dc.contributor.author Lubos, Marie-Luise
dc.contributor.author Huang, Minzhao
dc.contributor.author Olsen, Rachel
dc.contributor.author Mushegian, Arcady
dc.contributor.author Slawson, Chad
dc.contributor.author Hardwidge, Philip R.
dc.date.accessioned 2013-03-21T13:42:45Z
dc.date.available 2013-03-21T13:42:45Z
dc.date.issued 2013-03-21
dc.identifier.uri http://hdl.handle.net/2097/15388
dc.description.abstract Modulation of NF-κB-dependent responses is critical to the success of attaching/effacing (A/E) human pathogenic E. coli (EPEC and EHEC) and the natural mouse pathogen Citrobacter rodentium. NleB, a highly conserved type III secretion system effector of A/E pathogens, suppresses NF-κB activation, but the underlying mechanisms are unknown. We identified the mammalian glycolysis enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as an NleB interacting protein. Further, we discovered that GAPDH interacts with the TNF receptor associated factor 2 (TRAF2), a protein required for TNF-α-mediated NF-κB activation, and regulates TRAF2 polyubiquitination. During infection, NleB functions as a translocated N-acetyl-D-glucosamine (O-GlcNAc) transferase that modifies GAPDH. NleB-mediated GAPDH O-GlcNAcylation disrupts the TRAF2-GAPDH interaction to suppress TRAF2 polyubiquitination and NF-κB activation. Eliminating NleB OGlcNAcylation activity attenuates C. rodentium colonization of mice. These data identify GAPDH as a TRAF2 signaling cofactor and reveal a virulence strategy employed by A/E pathogens to inhibit NF-κB dependent host innate immune responses. en_US
dc.language.iso en_US en_US
dc.relation.uri http://www.sciencedirect.com/science/article/pii/S1931312812004246 en_US
dc.subject NF-κB en_US
dc.subject NleB en_US
dc.subject Glycosyltransferase en_US
dc.subject GAPDH en_US
dc.title NleB, a bacterial effector with glycosyltransferase activity targets GADPH function to inhibit NF-κB activation en_US
dc.type Article (author version) en_US
dc.date.published 2013 en_US
dc.citation.doi doi:10.1016/j.chom.2012.11.010 en_US
dc.citation.epage 99 en_US
dc.citation.issue 1 en_US
dc.citation.jtitle Cell Host & Microbe en_US
dc.citation.spage 87 en_US
dc.citation.volume 13 en_US
dc.contributor.authoreid philiphardwidge en_US


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