GogB Is an Anti-Inflammatory Effector that Limits Tissue Damage during Salmonella Infection through Interaction with Human FBXO22 and Skp1

PLoS Pathogens

Ana Victoria C. Pilar¹  Colin A. Cooper¹  Sarah A. Reid-Yu¹  David T. Mulder¹  Brian K. Coombes¹ 

[1] Michael G. DeGroote Institute for Infectious Disease Research and the Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada

关键词: Salmonellosis;    Salmonella;    Inflammation;    Cecum;    HeLa cells;    Host cells;    Glutathione chromatography;    Macrophages;   

DOI  :  10.1371/journal.ppat.1002773

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY