ArticleMolecular microbiology2014
The 4-cysteine zinc-finger motif of the RNA polymerase regulator DksA serves as a thiol switch for sensing oxidative and nitrosative stress.
Article in Molecular microbiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 62 citations in OpenAlex.
- Host-microbiota-pathogen interactions drive Salmonella enterica serovar Typhimurium pathogenesis.Nature reviews. Microbiology · 2026Review
- DksA inhibitors against intracellular and persistentScience advances · 2026Article
- DksA, ppGpp, and RegAB Regulate Nitrate Respiration in Paracoccus denitrificans.Journal of bacteriology · 2023Article
- Gre factors help Salmonella adapt to oxidative stress by improving transcription elongation and fidelity of metabolic genes.PLoS biology · 2023Article
- Promiscuity of response regulators for thioredoxin steers bacterial virulence.Nature communications · 2022Article
- Transposon-Directed Insertion-Site Sequencing Reveals Glycolysis GeneAntioxidants (Basel, Switzerland) · 2022Article
- Interrelation between Stress Management and Secretion Systems ofPathogens (Basel, Switzerland) · 2022Article
- The Pseudomonas aeruginosa DksA1 protein is involved in HScientific reports · 2022Article
- Expression and structure of the Chlamydia trachomatis DksA ortholog.Pathogens and disease · 2022Article
- Nitric Oxide Inhibition of Rickettsia rickettsii.Infection and immunity · 2021Article
- Article
- Impact of the Resistance Responses to Stress Conditions Encountered in Food and Food Processing Environments on the Virulence and Growth Fitness of Non-TyphoidalFoods (Basel, Switzerland) · 2021Review
- Frontline Science: LPS-inducible SLC30A1 drives human macrophage-mediated zinc toxicity against intracellular Escherichia coli.Journal of leukocyte biology · 2021Article
- DksA-dependent regulation of RpoS contributes to Borrelia burgdorferi tick-borne transmission and mammalian infectivity.PLoS pathogens · 2021Article
- Mutational analysis of Escherichia coli GreA protein reveals new functional activity independent of antipause and lethal when overexpressed.Scientific reports · 2020Article
- Interactions between DksA and Stress-Responsive Alternative Sigma Factors Control Inorganic Polyphosphate Accumulation in Escherichia coli.Journal of bacteriology · 2020Article
- Transcriptome analysis reveals that the RNA polymerase-binding protein DksA1 has pleiotropic functions inThe Journal of biological chemistry · 2020Article
- SpoT Induces IntracellularmBio · 2020Article
- Bacillus subtilis FolE is sustained by the ZagA zinc metallochaperone and the alarmone ZTP under conditions of zinc deficiency.Molecular microbiology · 2019Article
- Spx, a versatile regulator of the Bacillus subtilis stress response.Current genetics · 2019Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
We show that thiols in the 4-cysteine zinc-finger motif of DksA, an RNA polymerase accessory protein known to regulate the stringent response, sense oxidative and nitrosative stress. Hydrogen peroxide- or nitric oxide (NO)-mediated modifications of thiols in the DksA 4-cysteine zinc-finger motif release the metal cofactor and drive reversible changes in the α-helicity of the protein. Wild-type and relA spoT mutant Salmonella, but not isogenic dksA-deficient bacteria, experience the downregulation of r-protein and amino acid transport expression after NO treatment, suggesting that DksA can regulate gene expression in response to NO congeners independently of the ppGpp alarmone. Oxidative stress enhances the DksA-dependent repression of rpsM, while preventing the activation of livJ and hisG gene transcription that is supported by reduced, zinc-bound DksA. The inhibitory effects of oxidized DksA on transcription are reversible with dithiothreitol. Our investigations indicate that sensing of reactive species by DksA redox active thiols fine-tunes the expression of translational machinery and amino acid assimilation and biosynthesis in accord with the metabolic stress imposed by oxidative and nitrosative stress. Given the conservation of Cys(114) , and neighbouring hydrophobic and charged amino acids in DksA orthologues, phylogenetically diverse microorganisms may use the DksA thiol switch to regulate transcriptional responses to oxidative and nitrosative stress.
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