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Infect Immun. 1997 Sep; 65(9): 3725–3730.
PMCID: PMC175531

SlyA, a transcriptional regulator of Salmonella typhimurium, is required for resistance to oxidative stress and is expressed in the intracellular environment of macrophages.


Appropriate regulation of genes enables Salmonella typhimurium to adapt to the intracellular environment of the host. The Salmonella slyA gene is in a family of transcriptional regulators that may play an important role in this adaptation. We have previously shown that slyA mutant Salmonella strains are profoundly attenuated for virulence and do not survive in macrophages. In this study, we demonstrate that the expression of multiple Salmonella proteins is regulated by SlyA during stationary phase and during infection of macrophages. Both of these conditions also induced the expression of a slyA::lacZ transcriptional fusion. Expression of the slyA::lacZ transcriptional fusion increased 15-fold in stationary phase and was not dependent on the stationary-phase sigma factor, RpoS. slyA mutant Salmonella strains were sensitive to oxidative products of the respiratory burst, including hydrogen peroxide and the products of the redox cycling compound paraquat, but not to nitric oxide donors. These results suggest that the SlyA regulon is activated during infection of the host and is required for resistance to toxic oxidative products of the reticuloendothelial system.

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Selected References

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  • Abshire KZ, Neidhardt FC. Analysis of proteins synthesized by Salmonella typhimurium during growth within a host macrophage. J Bacteriol. 1993 Jun;175(12):3734–3743. [PMC free article] [PubMed]
  • Abshire KZ, Neidhardt FC. Growth rate paradox of Salmonella typhimurium within host macrophages. J Bacteriol. 1993 Jun;175(12):3744–3748. [PMC free article] [PubMed]
  • Babior BM. The respiratory burst of phagocytes. J Clin Invest. 1984 Mar;73(3):599–601. [PMC free article] [PubMed]
  • Bauer AW, Kirby WM, Sherris JC, Turck M. Antibiotic susceptibility testing by a standardized single disk method. Am J Clin Pathol. 1966 Apr;45(4):493–496. [PubMed]
  • Buchmeier NA, Heffron F. Induction of Salmonella stress proteins upon infection of macrophages. Science. 1990 May 11;248(4956):730–732. [PubMed]
  • Buchmeier NA, 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. [PMC free article] [PubMed]
  • Chen CY, Buchmeier NA, Libby S, Fang FC, Krause M, Guiney DG. Central regulatory role for the RpoS sigma factor in expression of Salmonella dublin plasmid virulence genes. J Bacteriol. 1995 Sep;177(18):5303–5309. [PMC free article] [PubMed]
  • Chen CY, Eckmann L, Libby SJ, Fang FC, Okamoto S, Kagnoff MF, Fierer J, Guiney DG. Expression of Salmonella typhimurium rpoS and rpoS-dependent genes in the intracellular environment of eukaryotic cells. Infect Immun. 1996 Nov;64(11):4739–4743. [PMC free article] [PubMed]
  • Cohen SN, Chang AC. Revised interpretation of the origin of the pSC101 plasmid. J Bacteriol. 1977 Nov;132(2):734–737. [PMC free article] [PubMed]
  • Daniels JJ, Autenrieth IB, Ludwig A, Goebel W. The gene slyA of Salmonella typhimurium is required for destruction of M cells and intracellular survival but not for invasion or colonization of the murine small intestine. Infect Immun. 1996 Dec;64(12):5075–5084. [PMC free article] [PubMed]
  • De Groote MA, Fang FC. NO inhibitions: antimicrobial properties of nitric oxide. Clin Infect Dis. 1995 Oct;21 (Suppl 2):S162–S165. [PubMed]
  • De Groote MA, Granger D, Xu Y, Campbell G, Prince R, Fang FC. 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. [PMC free article] [PubMed]
  • De Groote MA, Testerman T, Xu Y, Stauffer G, Fang FC. Homocysteine antagonism of nitric oxide-related cytostasis in Salmonella typhimurium. Science. 1996 Apr 19;272(5260):414–417. [PubMed]
  • Fang FC, Libby SJ, Buchmeier NA, Loewen PC, Switala J, Harwood J, Guiney DG. The alternative sigma factor katF (rpoS) regulates Salmonella virulence. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11978–11982. [PMC free article] [PubMed]
  • Farrington JA, Ebert M, Land EJ, Fletcher K. Bipyridylium quaternary salts and related compounds. V. Pulse radiolysis studies of the reaction of paraquat radical with oxygen. Implications for the mode of action of bipyridyl herbicides. Biochim Biophys Acta. 1973 Sep 26;314(3):372–381. [PubMed]
  • Fields PI, Groisman EA, Heffron F. A Salmonella locus that controls resistance to microbicidal proteins from phagocytic cells. Science. 1989 Feb 24;243(4894 Pt 1):1059–1062. [PubMed]
  • Fields PI, Swanson RV, Haidaris CG, 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. [PMC free article] [PubMed]
  • Fierer J, Eckmann L, Fang F, Pfeifer C, Finlay BB, Guiney D. Expression of the Salmonella virulence plasmid gene spvB in cultured macrophages and nonphagocytic cells. Infect Immun. 1993 Dec;61(12):5231–5236. [PMC free article] [PubMed]
  • Guiney DG, Libby S, Fang FC, Krause M, Fierer J. Growth-phase regulation of plasmid virulence genes in Salmonella. Trends Microbiol. 1995 Jul;3(7):275–279. [PubMed]
  • Guzman LM, Belin D, Carson MJ, Beckwith J. Tight regulation, modulation, and high-level expression by vectors containing the arabinose PBAD promoter. J Bacteriol. 1995 Jul;177(14):4121–4130. [PMC free article] [PubMed]
  • Hassan HM, Fridovich I. Superoxide radical and the oxygen enhancement of the toxicity of paraquat in Escherichia coli. J Biol Chem. 1978 Nov 25;253(22):8143–8148. [PubMed]
  • Jain VK, Magrath IT. A chemiluminescent assay for quantitation of beta-galactosidase in the femtogram range: application to quantitation of beta-galactosidase in lacZ-transfected cells. Anal Biochem. 1991 Nov 15;199(1):119–124. [PubMed]
  • Libby SJ, Goebel W, Ludwig A, Buchmeier N, Bowe F, Fang FC, Guiney DG, Songer JG, Heffron F. A cytolysin encoded by Salmonella is required for survival within macrophages. Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):489–493. [PMC free article] [PubMed]
  • Miller PF, Sulavik MC. Overlaps and parallels in the regulation of intrinsic multiple-antibiotic resistance in Escherichia coli. Mol Microbiol. 1996 Aug;21(3):441–448. [PubMed]
  • Miller RA, Britigan BE. Role of oxidants in microbial pathophysiology. Clin Microbiol Rev. 1997 Jan;10(1):1–18. [PMC free article] [PubMed]
  • Nikaido H. Multidrug efflux pumps of gram-negative bacteria. J Bacteriol. 1996 Oct;178(20):5853–5859. [PMC free article] [PubMed]
  • Oscarsson J, Mizunoe Y, Uhlin BE, Haydon DJ. Induction of haemolytic activity in Escherichia coli by the slyA gene product. Mol Microbiol. 1996 Apr;20(1):191–199. [PubMed]
  • Stamler JS. Redox signaling: nitrosylation and related target interactions of nitric oxide. Cell. 1994 Sep 23;78(6):931–936. [PubMed]
  • Storz G, Tartaglia LA, Farr SB, Ames BN. Bacterial defenses against oxidative stress. Trends Genet. 1990 Nov;6(11):363–368. [PubMed]
  • Sulavik MC, Dazer M, Miller PF. The Salmonella typhimurium mar locus: molecular and genetic analyses and assessment of its role in virulence. J Bacteriol. 1997 Mar;179(6):1857–1866. [PMC free article] [PubMed]
  • Valdivia RH, Falkow S. Bacterial genetics by flow cytometry: rapid isolation of Salmonella typhimurium acid-inducible promoters by differential fluorescence induction. Mol Microbiol. 1996 Oct;22(2):367–378. [PubMed]

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