Promiscuity of response regulators for thioredoxin steers bacterial virulence

The exquisite specificity between a sensor kinase and its cognate response regulator ensures faithful partner selectivity within two-component pairs concurrently firing in a single bacterium, minimizing crosstalk with other members of this conserved family of paralogous proteins. We show that conser...

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Bibliographic Details
Published in:Nature communications Vol. 13; no. 1; pp. 6210 - 15
Main Authors: Kim, Ju-Sim, Born, Alexandra, Till, James Karl A., Liu, Lin, Kant, Sashi, Henen, Morkos A., Vögeli, Beat, Vázquez-Torres, Andrés
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 20.10.2022
Nature Publishing Group
Nature Portfolio
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Allosteric properties
Animals
Bacteria
Bacterial Outer Membrane Proteins - metabolism
Bacterial Proteins - metabolism
DNA
DNA-directed RNA polymerase
EnvZ protein
Escherichia coli Proteins - metabolism
Gene Expression Regulation, Bacterial
Humanities and Social Sciences
Hydrophobicity
In vivo methods and tests
Information flow
Kinases
Macrophages
Mice
multidisciplinary
OmpR protein
Pathogenicity
Pathogens
Proteins
Regulators
Residues
RNA polymerase
Salmonella
Science
Science (multidisciplinary)
Selectivity
Signalling systems
Thioredoxin
Thioredoxins - genetics
Thioredoxins - metabolism
Transcription Factors - metabolism
Virulence
ISSN:2041-1723, 2041-1723
Online Access:Get full text
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Summary:The exquisite specificity between a sensor kinase and its cognate response regulator ensures faithful partner selectivity within two-component pairs concurrently firing in a single bacterium, minimizing crosstalk with other members of this conserved family of paralogous proteins. We show that conserved hydrophobic and charged residues on the surface of thioredoxin serve as a docking station for structurally diverse response regulators. Using the OmpR protein, we identify residues in the flexible linker and the C-terminal β-hairpin that enable associations of this archetypical response regulator with thioredoxin, but are dispensable for interactions of this transcription factor to its cognate sensor kinase EnvZ, DNA or RNA polymerase. Here we show that the promiscuous interactions of response regulators with thioredoxin foster the flow of information through otherwise highly dedicated two-component signaling systems, thereby enabling both the transcription of Salmonella pathogenicity island-2 genes as well as growth of this intracellular bacterium in macrophages and mice. The response regulator SsrB, a master activator of the Salmonella pathogenicity island-2 gene cluster, is under allosteric control of thioredoxin. Authors utilise in vitro and in vivo models to investigate if other members of the response regulator family might have adopted thioredoxin as a regulator.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-022-33983-6