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

Pilar, Ana Victoria C., Reid-Yu, Sarah A., Cooper, Colin A. ORCID: https://orcid.org/0000-0003-2013-8042, Mulder, David T. and Coombes, Brian K. (2012) GogB is an anti-inflammatory effector that limits tissue damage during Salmonella infection through interaction with human FBXO22 and Skp1. PLoS Pathogens, 8 (6). ISSN 1553-7366

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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.

Item Type:	Article
Additional Information:	© 2012 Pilar et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Uncontrolled Keywords:	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
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies
Depositing User:	Pure Connector
Date Deposited:	20 Jan 2014 15:58
Last Modified:	24 Oct 2022 05:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/46122
DOI:	10.1371/journal.ppat.1002773

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