Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1997 Dec;65(12):5371–5375. doi: 10.1128/iai.65.12.5371-5375.1997

The transcriptional regulator SoxS is required for resistance of Salmonella typhimurium to paraquat but not for virulence in mice.

F C Fang 1, A Vazquez-Torres 1, Y Xu 1
PMCID: PMC175777  PMID: 9393844

Abstract

In Escherichia coli, the SoxRS regulon is required for resistance to redox-cycling agents which elevate cytosolic superoxide levels, as well as for resistance to nitric oxide-dependent macrophage killing. In Salmonella typhimurium, SoxS is also required for enhanced expression of Mn-superoxide dismutase and resistance to paraquat, but not for resistance to nitric oxide donor compounds in vitro, resistance to macrophage killing, or virulence in mice. Differences in other antioxidant defense systems or compensation by homologous regulons may account for species-specific differences in the role of SoxS.

Full Text

The Full Text of this article is available as a PDF (758.7 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amábile-Cuevas C. F., Demple B. Molecular characterization of the soxRS genes of Escherichia coli: two genes control a superoxide stress regulon. Nucleic Acids Res. 1991 Aug 25;19(16):4479–4484. doi: 10.1093/nar/19.16.4479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ariza R. R., Li Z., Ringstad N., Demple B. Activation of multiple antibiotic resistance and binding of stress-inducible promoters by Escherichia coli Rob protein. J Bacteriol. 1995 Apr;177(7):1655–1661. doi: 10.1128/jb.177.7.1655-1661.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Asako H., Nakajima H., Kobayashi K., Kobayashi M., Aono R. Organic solvent tolerance and antibiotic resistance increased by overexpression of marA in Escherichia coli. Appl Environ Microbiol. 1997 Apr;63(4):1428–1433. doi: 10.1128/aem.63.4.1428-1433.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bauer A. W., Kirby W. M., Sherris J. C., Turck M. Antibiotic susceptibility testing by a standardized single disk method. Am J Clin Pathol. 1966 Apr;45(4):493–496. [PubMed] [Google Scholar]
  5. Beauchamp C., Fridovich I. Superoxide dismutase: improved assays and an assay applicable to acrylamide gels. Anal Biochem. 1971 Nov;44(1):276–287. doi: 10.1016/0003-2697(71)90370-8. [DOI] [PubMed] [Google Scholar]
  6. Brunelli L., Crow J. P., Beckman J. S. The comparative toxicity of nitric oxide and peroxynitrite to Escherichia coli. Arch Biochem Biophys. 1995 Jan 10;316(1):327–334. doi: 10.1006/abbi.1995.1044. [DOI] [PubMed] [Google Scholar]
  7. Buchmeier N. A., Heffron F. Intracellular survival of wild-type Salmonella typhimurium and macrophage-sensitive mutants in diverse populations of macrophages. Infect Immun. 1989 Jan;57(1):1–7. doi: 10.1128/iai.57.1.1-7.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Buchmeier N. A., Lipps C. J., So M. Y., Heffron F. Recombination-deficient mutants of Salmonella typhimurium are avirulent and sensitive to the oxidative burst of macrophages. Mol Microbiol. 1993 Mar;7(6):933–936. doi: 10.1111/j.1365-2958.1993.tb01184.x. [DOI] [PubMed] [Google Scholar]
  9. Chou J. H., Greenberg J. T., Demple B. Posttranscriptional repression of Escherichia coli OmpF protein in response to redox stress: positive control of the micF antisense RNA by the soxRS locus. J Bacteriol. 1993 Feb;175(4):1026–1031. doi: 10.1128/jb.175.4.1026-1031.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cohen S. P., Hächler H., Levy S. B. Genetic and functional analysis of the multiple antibiotic resistance (mar) locus in Escherichia coli. J Bacteriol. 1993 Mar;175(5):1484–1492. doi: 10.1128/jb.175.5.1484-1492.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cohen S. P., Levy S. B., Foulds J., Rosner J. L. Salicylate induction of antibiotic resistance in Escherichia coli: activation of the mar operon and a mar-independent pathway. J Bacteriol. 1993 Dec;175(24):7856–7862. doi: 10.1128/jb.175.24.7856-7862.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Compan I., Touati D. Interaction of six global transcription regulators in expression of manganese superoxide dismutase in Escherichia coli K-12. J Bacteriol. 1993 Mar;175(6):1687–1696. doi: 10.1128/jb.175.6.1687-1696.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. De Groote M. A., Granger D., Xu Y., Campbell G., Prince R., Fang F. C. Genetic and redox determinants of nitric oxide cytotoxicity in a Salmonella typhimurium model. Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6399–6403. doi: 10.1073/pnas.92.14.6399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. De Groote M. A., Testerman T., Xu Y., Stauffer G., Fang F. C. Homocysteine antagonism of nitric oxide-related cytostasis in Salmonella typhimurium. Science. 1996 Apr 19;272(5260):414–417. doi: 10.1126/science.272.5260.414. [DOI] [PubMed] [Google Scholar]
  15. Demple B. Redox signaling and gene control in the Escherichia coli soxRS oxidative stress regulon--a review. Gene. 1996 Nov 7;179(1):53–57. doi: 10.1016/s0378-1119(96)00329-0. [DOI] [PubMed] [Google Scholar]
  16. Denicola A., Souza J. M., Radi R., Lissi E. Nitric oxide diffusion in membranes determined by fluorescence quenching. Arch Biochem Biophys. 1996 Apr 1;328(1):208–212. doi: 10.1006/abbi.1996.0162. [DOI] [PubMed] [Google Scholar]
  17. Ding H., Hidalgo E., Demple B. The redox state of the [2Fe-2S] clusters in SoxR protein regulates its activity as a transcription factor. J Biol Chem. 1996 Dec 27;271(52):33173–33175. doi: 10.1074/jbc.271.52.33173. [DOI] [PubMed] [Google Scholar]
  18. Drapier J. C., Hibbs J. B., Jr Differentiation of murine macrophages to express nonspecific cytotoxicity for tumor cells results in L-arginine-dependent inhibition of mitochondrial iron-sulfur enzymes in the macrophage effector cells. J Immunol. 1988 Apr 15;140(8):2829–2838. [PubMed] [Google Scholar]
  19. Dukan S., Dadon S., Smulski D. R., Belkin S. Hypochlorous acid activates the heat shock and soxRS systems of Escherichia coli. Appl Environ Microbiol. 1996 Nov;62(11):4003–4008. doi: 10.1128/aem.62.11.4003-4008.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Fang F. C., Libby S. J., Buchmeier N. A., Loewen P. C., Switala J., Harwood J., Guiney D. G. The alternative sigma factor katF (rpoS) regulates Salmonella virulence. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11978–11982. doi: 10.1073/pnas.89.24.11978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Fang F. C. Perspectives series: host/pathogen interactions. Mechanisms of nitric oxide-related antimicrobial activity. J Clin Invest. 1997 Jun 15;99(12):2818–2825. doi: 10.1172/JCI119473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Fields P. I., Swanson R. V., Haidaris C. G., Heffron F. Mutants of Salmonella typhimurium that cannot survive within the macrophage are avirulent. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5189–5193. doi: 10.1073/pnas.83.14.5189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Finlay B. B., Falkow S. Salmonella as an intracellular parasite. Mol Microbiol. 1989 Dec;3(12):1833–1841. doi: 10.1111/j.1365-2958.1989.tb00170.x. [DOI] [PubMed] [Google Scholar]
  24. Gambino L., Gracheck S. J., Miller P. F. Overexpression of the MarA positive regulator is sufficient to confer multiple antibiotic resistance in Escherichia coli. J Bacteriol. 1993 May;175(10):2888–2894. doi: 10.1128/jb.175.10.2888-2894.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Gaudu P., Moon N., Weiss B. Regulation of the soxRS oxidative stress regulon. Reversible oxidation of the Fe-S centers of SoxR in vivo. J Biol Chem. 1997 Feb 21;272(8):5082–5086. doi: 10.1074/jbc.272.8.5082. [DOI] [PubMed] [Google Scholar]
  26. George A. M., Hall R. M., Stokes H. W. Multidrug resistance in Klebsiella pneumoniae: a novel gene, ramA, confers a multidrug resistance phenotype in Escherichia coli. Microbiology. 1995 Aug;141(Pt 8):1909–1920. doi: 10.1099/13500872-141-8-1909. [DOI] [PubMed] [Google Scholar]
  27. Greenberg J. T., Chou J. H., Monach P. A., Demple B. Activation of oxidative stress genes by mutations at the soxQ/cfxB/marA locus of Escherichia coli. J Bacteriol. 1991 Jul;173(14):4433–4439. doi: 10.1128/jb.173.14.4433-4439.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Greenberg J. T., Monach P., Chou J. H., Josephy P. D., Demple B. Positive control of a global antioxidant defense regulon activated by superoxide-generating agents in Escherichia coli. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6181–6185. doi: 10.1073/pnas.87.16.6181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Gruer M. J., Guest J. R. Two genetically-distinct and differentially-regulated aconitases (AcnA and AcnB) in Escherichia coli. Microbiology. 1994 Oct;140(Pt 10):2531–2541. doi: 10.1099/00221287-140-10-2531. [DOI] [PubMed] [Google Scholar]
  30. Hanahan D. Studies on transformation of Escherichia coli with plasmids. J Mol Biol. 1983 Jun 5;166(4):557–580. doi: 10.1016/s0022-2836(83)80284-8. [DOI] [PubMed] [Google Scholar]
  31. Hassan H. M., Sun H. C. Regulatory roles of Fnr, Fur, and Arc in expression of manganese-containing superoxide dismutase in Escherichia coli. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3217–3221. doi: 10.1073/pnas.89.8.3217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Hidalgo E., Demple B. An iron-sulfur center essential for transcriptional activation by the redox-sensing SoxR protein. EMBO J. 1994 Jan 1;13(1):138–146. doi: 10.1002/j.1460-2075.1994.tb06243.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Ishida H., Fuziwara H., Kaibori Y., Horiuchi T., Sato K., Osada Y. Cloning of multidrug resistance gene pqrA from Proteus vulgaris. Antimicrob Agents Chemother. 1995 Feb;39(2):453–457. doi: 10.1128/aac.39.2.453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Jair K. W., Martin R. G., Rosner J. L., Fujita N., Ishihama A., Wolf R. E., Jr Purification and regulatory properties of MarA protein, a transcriptional activator of Escherichia coli multiple antibiotic and superoxide resistance promoters. J Bacteriol. 1995 Dec;177(24):7100–7104. doi: 10.1128/jb.177.24.7100-7104.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Jair K. W., Yu X., Skarstad K., Thöny B., Fujita N., Ishihama A., Wolf R. E., Jr Transcriptional activation of promoters of the superoxide and multiple antibiotic resistance regulons by Rob, a binding protein of the Escherichia coli origin of chromosomal replication. J Bacteriol. 1996 May;178(9):2507–2513. doi: 10.1128/jb.178.9.2507-2513.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Kakeda M., Ueguchi C., Yamada H., Mizuno T. An Escherichia coli curved DNA-binding protein whose expression is affected by the stationary phase-specific sigma factor sigma S. Mol Gen Genet. 1995 Sep 20;248(5):629–634. doi: 10.1007/BF02423459. [DOI] [PubMed] [Google Scholar]
  37. Kimura T., Nishioka H. Intracellular generation of superoxide by copper sulphate in Escherichia coli. Mutat Res. 1997 Mar 17;389(2-3):237–242. doi: 10.1016/s1383-5718(96)00153-2. [DOI] [PubMed] [Google Scholar]
  38. Koh Y. S., Choih J., Lee J. H., Roe J. H. Regulation of the ribA gene encoding GTP cyclohydrolase II by the soxRS locus in Escherichia coli. Mol Gen Genet. 1996 Jul 19;251(5):591–598. doi: 10.1007/BF02173649. [DOI] [PubMed] [Google Scholar]
  39. Koh Y. S., Roe J. H. Dual regulation of the paraquat-inducible gene pqi-5 by SoxS and RpoS in Escherichia coli. Mol Microbiol. 1996 Oct;22(1):53–61. doi: 10.1111/j.1365-2958.1996.tb02655.x. [DOI] [PubMed] [Google Scholar]
  40. Li Z., Demple B. Sequence specificity for DNA binding by Escherichia coli SoxS and Rob proteins. Mol Microbiol. 1996 Jun;20(5):937–945. doi: 10.1111/j.1365-2958.1996.tb02535.x. [DOI] [PubMed] [Google Scholar]
  41. Liochev S. I., Fridovich I. Fumarase C, the stable fumarase of Escherichia coli, is controlled by the soxRS regulon. Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):5892–5896. doi: 10.1073/pnas.89.13.5892. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Liochev S. I., Hausladen A., Beyer W. F., Jr, Fridovich I. NADPH: ferredoxin oxidoreductase acts as a paraquat diaphorase and is a member of the soxRS regulon. Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1328–1331. doi: 10.1073/pnas.91.4.1328. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Macinga D. R., Parojcic M. M., Rather P. N. Identification and analysis of aarP, a transcriptional activator of the 2'-N-acetyltransferase in Providencia stuartii. J Bacteriol. 1995 Jun;177(12):3407–3413. doi: 10.1128/jb.177.12.3407-3413.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Miller P. F., Gambino L. F., Sulavik M. C., Gracheck S. J. Genetic relationship between soxRS and mar loci in promoting multiple antibiotic resistance in Escherichia coli. Antimicrob Agents Chemother. 1994 Aug;38(8):1773–1779. doi: 10.1128/aac.38.8.1773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Miller P. F., Sulavik M. C. Overlaps and parallels in the regulation of intrinsic multiple-antibiotic resistance in Escherichia coli. Mol Microbiol. 1996 Aug;21(3):441–448. doi: 10.1111/j.1365-2958.1996.tb02553.x. [DOI] [PubMed] [Google Scholar]
  46. Mouy R., Fischer A., Vilmer E., Seger R., Griscelli C. Incidence, severity, and prevention of infections in chronic granulomatous disease. J Pediatr. 1989 Apr;114(4 Pt 1):555–560. doi: 10.1016/s0022-3476(89)80693-6. [DOI] [PubMed] [Google Scholar]
  47. Nakajima H., Kobayashi K., Kobayashi M., Asako H., Aono R. Overexpression of the robA gene increases organic solvent tolerance and multiple antibiotic and heavy metal ion resistance in Escherichia coli. Appl Environ Microbiol. 1995 Jun;61(6):2302–2307. doi: 10.1128/aem.61.6.2302-2307.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Nunoshiba T., DeRojas-Walker T., Tannenbaum S. R., Demple B. Roles of nitric oxide in inducible resistance of Escherichia coli to activated murine macrophages. Infect Immun. 1995 Mar;63(3):794–798. doi: 10.1128/iai.63.3.794-798.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Nunoshiba T., deRojas-Walker T., Wishnok J. S., Tannenbaum S. R., Demple B. Activation by nitric oxide of an oxidative-stress response that defends Escherichia coli against activated macrophages. Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):9993–9997. doi: 10.1073/pnas.90.21.9993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Rosner J. L., Slonczewski J. L. Dual regulation of inaA by the multiple antibiotic resistance (mar) and superoxide (soxRS) stress response systems of Escherichia coli. J Bacteriol. 1994 Oct;176(20):6262–6269. doi: 10.1128/jb.176.20.6262-6269.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Schnell S., Steinman H. M. Function and stationary-phase induction of periplasmic copper-zinc superoxide dismutase and catalase/peroxidase in Caulobacter crescentus. J Bacteriol. 1995 Oct;177(20):5924–5929. doi: 10.1128/jb.177.20.5924-5929.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Schollmeier K., Hillen W. Transposon Tn10 contains two structural genes with opposite polarity between tetA and IS10R. J Bacteriol. 1984 Nov;160(2):499–503. doi: 10.1128/jb.160.2.499-503.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Simon R., O'Connell M., Labes M., Pühler A. Plasmid vectors for the genetic analysis and manipulation of rhizobia and other gram-negative bacteria. Methods Enzymol. 1986;118:640–659. doi: 10.1016/0076-6879(86)18106-7. [DOI] [PubMed] [Google Scholar]
  54. Tsaneva I. R., Weiss B. soxR, a locus governing a superoxide response regulon in Escherichia coli K-12. J Bacteriol. 1990 Aug;172(8):4197–4205. doi: 10.1128/jb.172.8.4197-4205.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Vazquez-Torres A., Jones-Carson J., Balish E. Peroxynitrite contributes to the candidacidal activity of nitric oxide-producing macrophages. Infect Immun. 1996 Aug;64(8):3127–3133. doi: 10.1128/iai.64.8.3127-3133.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Wu J., Weiss B. Two divergently transcribed genes, soxR and soxS, control a superoxide response regulon of Escherichia coli. J Bacteriol. 1991 May;173(9):2864–2871. doi: 10.1128/jb.173.9.2864-2871.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Wu J., Weiss B. Two-stage induction of the soxRS (superoxide response) regulon of Escherichia coli. J Bacteriol. 1992 Jun;174(12):3915–3920. doi: 10.1128/jb.174.12.3915-3920.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES