title: GogB is an anti-inflammatory effector that limits tissue damage during Salmonella infection through interaction with human FBXO22 and Skp1.
abstract: Bacterial pathogens often manipulate host immune pathways to establish acute and chronic infection. Many Gram-negative bacteria do this by secreting effector proteins through a type III secretion system that alter the host response to the pathogen. In this study, we determined that the phage-encoded GogB effector protein in Salmonella targets the host SCF E3 type ubiquitin ligase through an interaction with Skp1 and the human F-box only 22 (FBXO22) protein. Domain mapping and functional knockdown studies indicated that GogB-containing bacteria inhibited IκB degradation and NFκB activation in macrophages, which required Skp1 and a eukaryotic-like F-box motif in the C-terminal domain of GogB. GogB-deficient Salmonella were unable to limit NFκB activation, which lead to increased proinflammatory responses in infected mice accompanied by extensive tissue damage and enhanced colonization in the gut during long-term chronic infections. We conclude that GogB is an anti-inflammatory effector that helps regulate inflammation-enhanced colonization by limiting tissue damage during infection.
authors: Michael G. DeGroote Institute for Infectious Disease Research and the Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
authors: Ana Victoria C
authors: AV
authors: Pilar
authors: Sarah A
authors: SA
authors: Reid-Yu
authors: Colin A
authors: CA
authors: Cooper
authors: David T
authors: DT
authors: Mulder
authors: Brian K
authors: BK
authors: Coombes
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism*; D015153:Blotting, Western; D044783:F-Box Proteins / Q000276:immunology / Q000378:metabolism*; D005260:Female; D055785:Gene Knockdown Techniques; D022761:Gene Transfer, Horizontal; D006790:Host-Parasite Interactions / Q000276:immunology*; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D018160:Receptors, Cytoplasmic and Nuclear / Q000276:immunology / Q000378:metabolism*; D044786:S-Phase Kinase-Associated Proteins / Q000276:immunology / Q000378:metabolism*; D012480:Salmonella Infections / Q000276:immunology / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D044783:F-Box Proteins; C561886:FBXO22 protein, human; D016328:NF-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D044786:S-Phase Kinase-Associated Proteins; C097351:SKP1 protein, human