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The QseG lipoprotein impacts the virulence of enterohemorrhagic E. coli and Citrobacter rodentium and regulates flagellar phase variation in Salmonella enterica serovar Typhimurium

Cameron, E, Gruber, C, Ritchie, Jennifer, Waldor, M and Sperandio, V (2018) The QseG lipoprotein impacts the virulence of enterohemorrhagic E. coli and Citrobacter rodentium and regulates flagellar phase variation in Salmonella enterica serovar Typhimurium Infection and Immunity.

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Abstract

The QseEF histidine kinase/response regulator system modulates expression of enterohemorrhagic E. coli (EHEC) and Salmonella enterica serovar Typhimurium (Stm) virulence genes in response to the host neurotransmitters epinephrine and norepinephrine. QseG, which encodes an outer membrane lipoprotein, is co-transcribed with qseEF in these enteric pathogens, but there is little knowledge of its role in virulence. Here, we found that in EHEC QseG interacts with the type three secretion system (T3SS) gate protein SepL, and modulates the kinetics of attaching and effacing (AE) lesion formation on tissue-cultured cells. Moreover, an EHEC ΔqseG mutant had reduced intestinal colonization in the infant rabbit model. Additionally, in Citrobacter rodentium, an AE lesion-forming pathogen like EHEC, QseG is required for full virulence in a mouse model. In Stm, we found that QseG regulates the phase switch between the two flagellin types, FliC and FljB. In an Stm ΔqseG mutant, the phase variable promoter for fljB is preferentially switched into the ‘on’ position, leading to an overproduction of this ‘phase two’ flagellin. In infection of tissue-cultured cells, the ΔqseG Stm mutant provokes increased inflammatory cytokine production vs wild-type; in vivo, in a murine infection model, the ΔqseG strain caused a more severe inflammatory response, and was attenuated vs the wild-type strain. Collectively, our findings demonstrate that QseG is important for full virulence in several enteric pathogens and controls flagellar phase variation in Stm, and highlight both the complexity and conservation of the regulatory networks that control the virulence of enteric pathogens.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
Cameron, E
Gruber, C
Ritchie, Jenniferj.ritchie@surrey.ac.uk
Waldor, M
Sperandio, V
Date : 22 January 2018
Identification Number : 10.1128/IAI.00936-17
Copyright Disclaimer : Copyright © 2018 American Society for Microbiology. All Rights Reserved
Depositing User : Melanie Hughes
Date Deposited : 31 Jan 2018 10:32
Last Modified : 31 Jan 2018 10:32
URI: http://epubs.surrey.ac.uk/id/eprint/845714

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