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Crawford MA, Henard CA, Tapscott T, et al. DksA-Dependent Transcriptional Regulation in Salmonella Experiencing Nitrosative Stress. Front Microbiol. 2016;7:444doi: 10.3389/fmicb.2016.00444.
Crawford, M. A., Henard, C. A., Tapscott, T., Porwollik, S., McClelland, M., & Vázquez-Torres, A. (2016). DksA-Dependent Transcriptional Regulation in Salmonella Experiencing Nitrosative Stress. Frontiers in microbiology, 7444. https://doi.org/10.3389/fmicb.2016.00444
Crawford, Matthew A, et al. "DksA-Dependent Transcriptional Regulation in Salmonella Experiencing Nitrosative Stress." Frontiers in microbiology vol. 7 (2016): 444. doi: https://doi.org/10.3389/fmicb.2016.00444
Crawford MA, Henard CA, Tapscott T, Porwollik S, McClelland M, Vázquez-Torres A. DksA-Dependent Transcriptional Regulation in Salmonella Experiencing Nitrosative Stress. Front Microbiol. 2016 Mar 31;7:444. doi: 10.3389/fmicb.2016.00444. eCollection 2016. PMID: 27065993; PMCID: PMC4815678.
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Front Microbiol. 2016 Mar 31;7:444. doi: 10.3389/fmicb.2016.00444. eCollection 2016.

DksA-Dependent Transcriptional Regulation in Salmonella Experiencing Nitrosative Stress.

Frontiers in microbiology

Matthew A Crawford, Calvin A Henard, Timothy Tapscott, Steffen Porwollik, Michael McClelland, Andrés Vázquez-Torres

Affiliations

  1. Department of Immunology and Microbiology, University of Colorado School of Medicine Aurora, CO, USA.
  2. Molecular Biology Program, University of Colorado School of Medicine Aurora, CO, USA.
  3. Department of Pathology and Laboratory Medicine, University of California, Irvine Irvine, CA, USA.
  4. Department of Immunology and Microbiology, University of Colorado School of MedicineAurora, CO, USA; Veterans Affairs Eastern Colorado Health Care SystemDenver, CO, USA.

PMID: 27065993 PMCID: PMC4815678 DOI: 10.3389/fmicb.2016.00444

Abstract

Redox-based signaling is fundamental to the capacity of bacteria to sense, and respond to, nitrosative and oxidative stress encountered in natural and host environments. The conserved RNA polymerase regulatory protein DksA is a thiol-based sensor of reactive nitrogen and oxygen species. DksA-dependent transcriptional control promotes antinitrosative and antioxidative defenses that contribute to Salmonella pathogenesis. The specific adaptive changes mediated by DksA in response to reactive species, however, have not been elucidated. Herein, we characterize DksA-dependent changes in gene expression in Salmonella enterica experiencing nitrosative stress. Genome-wide expression analysis of wild-type and ΔdksA Salmonella exposed to the nitric oxide ((•)NO) donor DETA NONOate demonstrated (•)NO- and DksA-dependent regulatory control of 427 target genes. Transcriptional changes centered primarily on genes encoding aspects of cellular metabolism. Several antioxidants and oxidoreductases important in redox buffering, (•)NO detoxification, and damage repair were also observed to be up-regulated in an (•)NO- and DksA-dependent manner. Compared to wild-type bacteria, (•)NO-treated ΔdksA Salmonella exhibited a de-repression of genes encoding components of iron homeostasis and failed to activate sulfur assimilation and cysteine biosynthetic operons. As cysteine is integral to efficient antinitrosative and antioxidative defense and repair programs, we further examined the redox-responsive transcriptional control of cysteine biosynthesis by DksA. These investigations revealed that the activation of genes comprising cysteine biosynthesis also occurs in response to hydrogen peroxide, is dependent upon the redox-sensing zinc finger motif of DksA, and requires the transcriptional regulator CysB. Our observations demonstrate that DksA mediates global adaptation to nitrosative stress in Salmonella and provide unique insight into a novel regulatory mechanism by which cysteine biosynthesis is controlled in response to reactive oxygen and nitrogen species.

Keywords: DksA; Salmonella; cysteine; metabolism; nitric oxide; reactive nitrogen species (RNS); transcriptional regulation

References

  1. Infect Immun. 1999 Jan;67(1):436-8 - PubMed
  2. Nucleic Acids Res. 2014 Jun;42(10):6523-31 - PubMed
  3. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5189-93 - PubMed
  4. J Clin Invest. 1997 Jun 15;99(12):2818-25 - PubMed
  5. Proc Natl Acad Sci U S A. 2005 Jan 11;102(2):467-72 - PubMed
  6. Annu Rev Microbiol. 1993;47:597-626 - PubMed
  7. J Exp Med. 2000 Jul 17;192(2):227-36 - PubMed
  8. Infect Immun. 2012 Apr;80(4):1373-80 - PubMed
  9. Antioxid Redox Signal. 2011 Mar 15;14(6):1049-63 - PubMed
  10. J Biol Chem. 2008 Mar 21;283(12):7682-9 - PubMed
  11. J Biol Chem. 2016 Mar 11;291(11):5860-70 - PubMed
  12. Nat Rev Microbiol. 2012 Feb 16;10(3):203-12 - PubMed
  13. Mol Microbiol. 2013 Feb;87(3):609-22 - PubMed
  14. Mol Microbiol. 2000 May;36(4):775-83 - PubMed
  15. Front Microbiol. 2011 Apr 20;2:84 - PubMed
  16. Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16619-24 - PubMed
  17. J Biol Chem. 2010 Nov 19;285(47):36785-93 - PubMed
  18. Proc Natl Acad Sci U S A. 2007 May 15;104(20):8484-9 - PubMed
  19. Biochim Biophys Acta. 1999 May 5;1411(2-3):217-30 - PubMed
  20. Mol Microbiol. 2014 Feb;91(4):790-804 - PubMed
  21. Nat Protoc. 2009;4(1):44-57 - PubMed
  22. Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6640-5 - PubMed
  23. J Exp Med. 2000 Jul 17;192(2):237-48 - PubMed
  24. Cell Host Microbe. 2011 Jul 21;10(1):33-43 - PubMed

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