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


Authors: Gao, X; Wang, X; Pham TH; Feuerbacher LA; Lubos ML; Huang, M.; Olsen R; Mushegian A; Slawson, C. .; Hardwidge, PR
Article Title: NleB, a bacterial effector with glycosyltransferase activity, targets GAPDH function to inhibit NF-κB activation
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 O-GlcNAcylation 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.
Journal Title: Cell host & microbe
Volume: 13
Issue: 1
ISSN: 1934-6069
Publisher: Cell Press  
Date Published: 2013-01-16
Start Page: 87
End Page: 99
Identifier: 10.1016/j.chom.2012.11.010