Logo of jbacterPermissionsJournals.ASM.orgJournalJB ArticleJournal InfoAuthorsReviewers
J Bacteriol. May 1996; 178(9): 2572–2579.
PMCID: PMC177981

Acid shock induction of RpoS is mediated by the mouse virulence gene mviA of Salmonella typhimurium.


Salmonella typhimurium encounters a variety of acid stress situations during growth in host and nonhost environments. The organism can survive potentially lethal acid conditions (pH <4) if it is first able to adapt to mild or more moderate acid levels. The molecular events that occur during this adaptive process are collectively referred to as the acid tolerance response and vary depending on whether the cells are in log- or stationary-phase growth. The acid tolerance response of logarithmically growing cells includes the participation of an alternate sigma factor, sigmaS (RpoS), commonly associated with stationary-phase physiology. Of 51 acid shock proteins (ASPs) induced during shifts to pH 4.4, 8 are clearly dependent on sigmaS for production (I. S. Lee, J. Lin, H. K. Hall, B. Bearson, and J. W. Foster, Mol. Microbiol. 17:155-167, 1995). The acid shock induction of these proteins appears to be the result of an acid shock-induced increase in the level of sigmaS itself. We have discovered that one component of a potential signal transduction system responsible for inducing rpoS expression is the product of the mouse virulence gene mviA+. MviA exhibits extensive homology to the regulatory components of certain two-component signal transduction systems (W. H. Benjamin, Jr., and P. D. Hall, abstr. B-67, p. 38, in Abstracts of the 93rd General Meeting of the American Society for Microbiology 1993, 1993). Mutations in mviA (mviA::Km) caused the overproduction of sigmaS and sigmaS-dependent ASPs in logarithmically growing cells, as well as increases in tolerances to acid, heat, osmolarity and oxidative stresses and significant decreases in growth rate and colony size. Mutations in rpoS suppressed the mviA::Km-associated defects in growth rate, colony size, ASP production, and stress tolerance, suggesting that the effects of MviA on cell physiology occur via its control of sigmaS levels. Western blot (immunoblot) analyses of sigmaS produced from natural or arabinose-regulated promoters revealed that acid shock and MviA posttranscriptionally regulate sigmaS levels. Turnover experiments suggest that MviA regulates the stability of sigmaS protein rather than the translation of rpoS message. We propose a model in which MviA or its unknown signal transduction partner senses some consequence of acid shock, and probably other stresses, and signals the release of sigmaS from proteolysis. The increased concentration of sigmaS drives the elevated expression of the sigmaS-dependent ASPs, resulting in an increase in stress tolerance. The avirulent nature of mviA insertion mutants, therefore, appears to result from inappropriate sigmaS-dependent gene expression during pathogenesis.

Full Text

The Full Text of this article is available as a PDF (671K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • 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]
  • Aliabadi Z, Park YK, Slonczewski JL, Foster JW. Novel regulatory loci controlling oxygen- and pH-regulated gene expression in Salmonella typhimurium. J Bacteriol. 1988 Feb;170(2):842–851. [PMC free article] [PubMed]
  • Altuvia S, Almirón M, Huisman G, Kolter R, Storz G. The dps promoter is activated by OxyR during growth and by IHF and sigma S in stationary phase. Mol Microbiol. 1994 Jul;13(2):265–272. [PubMed]
  • Atlung T, Brøndsted L. Role of the transcriptional activator AppY in regulation of the cyx appA operon of Escherichia coli by anaerobiosis, phosphate starvation, and growth phase. J Bacteriol. 1994 Sep;176(17):5414–5422. [PMC free article] [PubMed]
  • Barth M, Marschall C, Muffler A, Fischer D, Hengge-Aronis R. Role for the histone-like protein H-NS in growth phase-dependent and osmotic regulation of sigma S and many sigma S-dependent genes in Escherichia coli. J Bacteriol. 1995 Jun;177(12):3455–3464. [PMC free article] [PubMed]
  • Benjamin WH, Jr, Hall P, Roberts SJ, Briles DE. The primary effect of the Ity locus is on the rate of growth of Salmonella typhimurium that are relatively protected from killing. J Immunol. 1990 Apr 15;144(8):3143–3151. [PubMed]
  • Benjamin WH, Jr, Yother J, Hall P, Briles DE. The Salmonella typhimurium locus mviA regulates virulence in Itys but not Ityr mice: functional mviA results in avirulence; mutant (nonfunctional) mviA results in virulence. J Exp Med. 1991 Nov 1;174(5):1073–1083. [PMC free article] [PubMed]
  • Booth IR. Regulation of cytoplasmic pH in bacteria. Microbiol Rev. 1985 Dec;49(4):359–378. [PMC free article] [PubMed]
  • Bösl M, Kersten H. Organization and functions of genes in the upstream region of tyrT of Escherichia coli: phenotypes of mutants with partial deletion of a new gene (tgs). J Bacteriol. 1994 Jan;176(1):221–231. [PMC free article] [PubMed]
  • Brøndsted L, Atlung T. Anaerobic regulation of the hydrogenase 1 (hya) operon of Escherichia coli. J Bacteriol. 1994 Sep;176(17):5423–5428. [PMC free article] [PubMed]
  • Dassa J, Fsihi H, Marck C, Dion M, Kieffer-Bontemps M, Boquet PL. A new oxygen-regulated operon in Escherichia coli comprises the genes for a putative third cytochrome oxidase and for pH 2.5 acid phosphatase (appA) Mol Gen Genet. 1991 Oct;229(3):341–352. [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]
  • Foster JW. Salmonella acid shock proteins are required for the adaptive acid tolerance response. J Bacteriol. 1991 Nov;173(21):6896–6902. [PMC free article] [PubMed]
  • Foster JW. The acid tolerance response of Salmonella typhimurium involves transient synthesis of key acid shock proteins. J Bacteriol. 1993 Apr;175(7):1981–1987. [PMC free article] [PubMed]
  • Foster JW. Low pH adaptation and the acid tolerance response of Salmonella typhimurium. Crit Rev Microbiol. 1995;21(4):215–237. [PubMed]
  • Foster JW, Hall HK. Adaptive acidification tolerance response of Salmonella typhimurium. J Bacteriol. 1990 Feb;172(2):771–778. [PMC free article] [PubMed]
  • Foster JW, Hall HK. Inducible pH homeostasis and the acid tolerance response of Salmonella typhimurium. J Bacteriol. 1991 Aug;173(16):5129–5135. [PMC free article] [PubMed]
  • Gulig PA, Doyle TJ. The Salmonella typhimurium virulence plasmid increases the growth rate of salmonellae in mice. Infect Immun. 1993 Feb;61(2):504–511. [PMC free article] [PubMed]
  • Hall HK, Karem KL, Foster JW. Molecular responses of microbes to environmental pH stress. Adv Microb Physiol. 1995;37:229–272. [PubMed]
  • Hengge-Aronis R, Fischer D. Identification and molecular analysis of glgS, a novel growth-phase-regulated and rpoS-dependent gene involved in glycogen synthesis in Escherichia coli. Mol Microbiol. 1992 Jul;6(14):1877–1886. [PubMed]
  • Hengge-Aronis R, Lange R, Henneberg N, Fischer D. Osmotic regulation of rpoS-dependent genes in Escherichia coli. J Bacteriol. 1993 Jan;175(1):259–265. [PMC free article] [PubMed]
  • Holley EA, Foster JW. Bacteriophage P22 as a vector for Mu mutagenesis in Salmonella typhimurium: isolation of nad-lac and pnc-lac gene fusions. J Bacteriol. 1982 Nov;152(2):959–962. [PMC free article] [PubMed]
  • Hughes KT, Roth JR. Transitory cis complementation: a method for providing transposition functions to defective transposons. Genetics. 1988 May;119(1):9–12. [PMC free article] [PubMed]
  • Kowarz L, Coynault C, Robbe-Saule V, Norel F. The Salmonella typhimurium katF (rpoS) gene: cloning, nucleotide sequence, and regulation of spvR and spvABCD virulence plasmid genes. J Bacteriol. 1994 Nov;176(22):6852–6860. [PMC free article] [PubMed]
  • Lange R, Barth M, Hengge-Aronis R. Complex transcriptional control of the sigma s-dependent stationary-phase-induced and osmotically regulated osmY (csi-5) gene suggests novel roles for Lrp, cyclic AMP (cAMP) receptor protein-cAMP complex, and integration host factor in the stationary-phase response of Escherichia coli. J Bacteriol. 1993 Dec;175(24):7910–7917. [PMC free article] [PubMed]
  • Lange R, Hengge-Aronis R. Growth phase-regulated expression of bolA and morphology of stationary-phase Escherichia coli cells are controlled by the novel sigma factor sigma S. J Bacteriol. 1991 Jul;173(14):4474–4481. [PMC free article] [PubMed]
  • Lange R, Hengge-Aronis R. Identification of a central regulator of stationary-phase gene expression in Escherichia coli. Mol Microbiol. 1991 Jan;5(1):49–59. [PubMed]
  • Lange R, Hengge-Aronis R. The cellular concentration of the sigma S subunit of RNA polymerase in Escherichia coli is controlled at the levels of transcription, translation, and protein stability. Genes Dev. 1994 Jul 1;8(13):1600–1612. [PubMed]
  • Lee IS, Lin J, Hall HK, Bearson B, Foster JW. The stationary-phase sigma factor sigma S (RpoS) is required for a sustained acid tolerance response in virulent Salmonella typhimurium. Mol Microbiol. 1995 Jul;17(1):155–167. [PubMed]
  • Lee IS, Slonczewski JL, Foster JW. A low-pH-inducible, stationary-phase acid tolerance response in Salmonella typhimurium. J Bacteriol. 1994 Mar;176(5):1422–1426. [PMC free article] [PubMed]
  • Leung KY, Finlay BB. Intracellular replication is essential for the virulence of Salmonella typhimurium. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11470–11474. [PMC free article] [PubMed]
  • Lissner CR, Weinstein DL, O'Brien AD. Mouse chromosome 1 Ity locus regulates microbicidal activity of isolated peritoneal macrophages against a diverse group of intracellular and extracellular bacteria. J Immunol. 1985 Jul;135(1):544–547. [PubMed]
  • Loewen PC, von Ossowski I, Switala J, Mulvey MR. KatF (sigma S) synthesis in Escherichia coli is subject to posttranscriptional regulation. J Bacteriol. 1993 Apr;175(7):2150–2153. [PMC free article] [PubMed]
  • Lomovskaya OL, Kidwell JP, Matin A. Characterization of the sigma 38-dependent expression of a core Escherichia coli starvation gene, pexB. J Bacteriol. 1994 Jul;176(13):3928–3935. [PMC free article] [PubMed]
  • Matin A. The molecular basis of carbon-starvation-induced general resistance in Escherichia coli. Mol Microbiol. 1991 Jan;5(1):3–10. [PubMed]
  • McCann MP, Fraley CD, Matin A. The putative sigma factor KatF is regulated posttranscriptionally during carbon starvation. J Bacteriol. 1993 Apr;175(7):2143–2149. [PMC free article] [PubMed]
  • Mulvey MR, Switala J, Borys A, Loewen PC. Regulation of transcription of katE and katF in Escherichia coli. J Bacteriol. 1990 Dec;172(12):6713–6720. [PMC free article] [PubMed]
  • Nguyen LH, Jensen DB, Thompson NE, Gentry DR, Burgess RR. In vitro functional characterization of overproduced Escherichia coli katF/rpoS gene product. Biochemistry. 1993 Oct 19;32(41):11112–11117. [PubMed]
  • O'Neal CR, Gabriel WM, Turk AK, Libby SJ, Fang FC, Spector MP. RpoS is necessary for both the positive and negative regulation of starvation survival genes during phosphate, carbon, and nitrogen starvation in Salmonella typhimurium. J Bacteriol. 1994 Aug;176(15):4610–4616. [PMC free article] [PubMed]
  • Robbe-Saule V, Coynault C, Norel F. The live oral typhoid vaccine Ty21a is a rpoS mutant and is susceptible to various environmental stresses. FEMS Microbiol Lett. 1995 Feb 15;126(2):171–176. [PubMed]
  • Schellhorn HE, Stones VL. Regulation of katF and katE in Escherichia coli K-12 by weak acids. J Bacteriol. 1992 Jul;174(14):4769–4776. [PMC free article] [PubMed]
  • Schweder T, Lee KH, Lomovskaya O, Matin A. Regulation of Escherichia coli starvation sigma factor (sigma s) by ClpXP protease. J Bacteriol. 1996 Jan;178(2):470–476. [PMC free article] [PubMed]
  • Spector MP, Aliabadi Z, Gonzalez T, Foster JW. Global control in Salmonella typhimurium: two-dimensional electrophoretic analysis of starvation-, anaerobiosis-, and heat shock-inducible proteins. J Bacteriol. 1986 Oct;168(1):420–424. [PMC free article] [PubMed]
  • Spector MP, Cubitt CL. Starvation-inducible loci of Salmonella typhimurium: regulation and roles in starvation-survival. Mol Microbiol. 1992 Jun;6(11):1467–1476. [PubMed]
  • Swords WE, Benjamin WH., Jr Mouse virulence gene A (mviA+) is a pleiotropic regulator of gene expression in Salmonella typhimurium. Ann N Y Acad Sci. 1994 Aug 15;730:295–296. [PubMed]
  • Takayanagi Y, Tanaka K, Takahashi H. Structure of the 5' upstream region and the regulation of the rpoS gene of Escherichia coli. Mol Gen Genet. 1994 Jun 3;243(5):525–531. [PubMed]
  • Tsai SP, Hartin RJ, Ryu J. Transformation in restriction-deficient Salmonella typhimurium LT2. J Gen Microbiol. 1989 Sep;135(9):2561–2567. [PubMed]
  • VOGEL HJ, BONNER DM. Acetylornithinase of Escherichia coli: partial purification and some properties. J Biol Chem. 1956 Jan;218(1):97–106. [PubMed]
  • Volkert MR, Hajec LI, Matijasevic Z, Fang FC, Prince R. Induction of the Escherichia coli aidB gene under oxygen-limiting conditions requires a functional rpoS (katF) gene. J Bacteriol. 1994 Dec;176(24):7638–7645. [PMC free article] [PubMed]
  • Weichart D, Lange R, Henneberg N, Hengge-Aronis R. Identification and characterization of stationary phase-inducible genes in Escherichia coli. Mol Microbiol. 1993 Oct;10(2):407–420. [PubMed]
  • Yamashino T, Ueguchi C, Mizuno T. Quantitative control of the stationary phase-specific sigma factor, sigma S, in Escherichia coli: involvement of the nucleoid protein H-NS. EMBO J. 1995 Feb 1;14(3):594–602. [PMC free article] [PubMed]
  • Zilberstein D, Agmon V, Schuldiner S, Padan E. The sodium/proton antiporter is part of the pH homeostasis mechanism in Escherichia coli. J Biol Chem. 1982 Apr 10;257(7):3687–3691. [PubMed]

Articles from Journal of Bacteriology are provided here courtesy of American Society for Microbiology (ASM)


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...