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Hydrogen peroxide\u2010 or nitric oxide (NO<\/jats:roman><\/jats:styled-content>)\u2010mediated modifications of thiols in the DksA<\/jats:styled-content> 4\u2010cysteine zinc\u2010finger motif release the metal cofactor and drive reversible changes in the \u03b1\u2010helicity of the protein. Wild\u2010type and relA<\/jats:italic><\/jats:styled-content> spoT<\/jats:italic><\/jats:styled-content><\/jats:italic> mutant S<\/jats:italic><\/jats:styled-content>almonella<\/jats:italic>, but not isogenic dksA<\/jats:italic><\/jats:styled-content>\u2010deficient bacteria, experience the downregulation of r\u2010protein and amino acid transport expression after NO<\/jats:roman><\/jats:styled-content> treatment, suggesting that DksA<\/jats:styled-content> can regulate gene expression in response to NO<\/jats:roman><\/jats:styled-content> congeners independently of the ppGpp<\/jats:styled-content> alarmone. Oxidative stress enhances the DksA<\/jats:styled-content>\u2010dependent repression of rpsM<\/jats:italic><\/jats:styled-content>, while preventing the activation of livJ<\/jats:italic><\/jats:styled-content> and hisG<\/jats:italic><\/jats:styled-content> gene transcription that is supported by reduced, zinc\u2010bound DksA<\/jats:styled-content>. The inhibitory effects of oxidized DksA<\/jats:styled-content> on transcription are reversible with dithiothreitol. Our investigations indicate that sensing of reactive species by DksA<\/jats:styled-content> redox active thiols fine\u2010tunes 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<\/jats:styled-content>114<\/jats:sup>, and neighbouring hydrophobic and charged amino acids in DksA<\/jats:styled-content> orthologues, phylogenetically diverse microorganisms may use the DksA<\/jats:styled-content> thiol switch to regulate transcriptional responses to oxidative and nitrosative stress.<\/jats:p>","DOI":"10.1111\/mmi.12498","type":"journal-article","created":{"date-parts":[[2013,12,20]],"date-time":"2013-12-20T07:22:46Z","timestamp":1387524166000},"page":"790-804","source":"Crossref","is-referenced-by-count":68,"title":["The 4\u2010cysteine zinc\u2010finger motif of the RNA<\/scp> polymerase regulator DksA<\/scp> serves as a thiol switch for sensing oxidative and nitrosative stress"],"prefix":"10.1111","volume":"91","author":[{"given":"Calvin A.","family":"Henard","sequence":"first","affiliation":[{"name":"Department of Microbiology University of Colorado School of Medicine Aurora CO 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