GogB is an anti-inflammatory effector that limits tissue damage during Salmonella infection through interaction with human FBXO22 and Skp1

Ana Victoria C. Pilar, Sarah A. Reid-Yu, Colin A. Cooper, David T. Mulder, Brian K. Coombes

Research output: Contribution to journalArticlepeer-review

68 Citations (Scopus)


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.
Original languageEnglish
Article numbere1002773
JournalPLoS Pathogens
Issue number6
Publication statusPublished - 28 Jun 2012


  • Animals
  • Bacterial Proteins
  • Blotting, Western
  • F-Box Proteins
  • Female
  • Gene Knockdown Techniques
  • Gene Transfer, Horizontal
  • Host-Parasite Interactions
  • Humans
  • Immunoprecipitation
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B
  • Real-Time Polymerase Chain Reaction
  • Receptors, Cytoplasmic and Nuclear
  • S-Phase Kinase-Associated Proteins
  • Salmonella Infections

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