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Proc Natl Acad Sci U S A. Jul 1989; 86(13): 5054–5058.
PMCID: PMC297555

A two-component regulatory system (phoP phoQ) controls Salmonella typhimurium virulence.

Abstract

We have determined that Salmonella typhimurium strains with mutations in the positive regulatory locus phoP are markedly attenuated in virulence for BALB/c mice. The DNA sequence for the phoP locus indicates that it is composed of two genes present in an operon, termed phoP and phoQ. The deduced amino acid sequence of the phoP and phoQ gene products are highly similar to other members of bacterial two-component transcriptional regulators that respond to environmental stimuli. S. typhimurium strains with transposon insertions that create transcriptional and translational gene fusions that require phoP and phoQ for expression have been isolated and have different chromosomal locations, indicating that this system is a regulon. One of these fusion strains, containing a mutation in a gene termed pagC, has a virulence defect. Other strains, including those containing mutations in the phoN gene, encoding an acid phosphatase, have wild-type virulence. Strains with pagC, phoP, or phoQ mutations have decreased survival in cultured mouse macrophages. When used as live vaccines in mice, strains with phoP or phoQ mutations afford partial protection to subsequent challenge by wild-type S. typhimurium.

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  • Carter PB, Collins FM. The route of enteric infection in normal mice. J Exp Med. 1974 May 1;139(5):1189–1203. [PMC free article] [PubMed]
  • Finlay BB, Falkow S. Virulence factors associated with Salmonella species. Microbiol Sci. 1988 Nov;5(11):324–328. [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]
  • Miller JF, Mekalanos JJ, Falkow S. Coordinate regulation and sensory transduction in the control of bacterial virulence. Science. 1989 Feb 17;243(4893):916–922. [PubMed]
  • Ronson CW, Nixon BT, Ausubel FM. Conserved domains in bacterial regulatory proteins that respond to environmental stimuli. Cell. 1987 Jun 5;49(5):579–581. [PubMed]
  • Bochner BR, Huang HC, Schieven GL, Ames BN. Positive selection for loss of tetracycline resistance. J Bacteriol. 1980 Aug;143(2):926–933. [PMC free article] [PubMed]
  • Monroe RS, Kredich NM. Isolation of Salmonella typhimurium cys genes by transduction with a library of recombinant plasmids packaged in bacteriophage P22HT capsids. J Bacteriol. 1988 Jan;170(1):42–47. [PMC free article] [PubMed]
  • Kukral AM, Strauch KL, Maurer RA, Miller CG. Genetic analysis in Salmonella typhimurium with a small collection of randomly spaced insertions of transposon Tn10 delta 16 delta 17. J Bacteriol. 1987 May;169(5):1787–1793. [PMC free article] [PubMed]
  • Kier LD, Weppelman R, Ames BN. Resolution and purification of three periplasmic phosphatases of Salmonella typhimurium. J Bacteriol. 1977 Apr;130(1):399–410. [PMC free article] [PubMed]
  • Manoil C, Beckwith J. TnphoA: a transposon probe for protein export signals. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8129–8133. [PMC free article] [PubMed]
  • Brickman E, Beckwith J. Analysis of the regulation of Escherichia coli alkaline phosphatase synthesis using deletions and phi80 transducing phages. J Mol Biol. 1975 Aug 5;96(2):307–316. [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]
  • Elliott T, Roth JR. Characterization of Tn10d-Cam: a transposition-defective Tn10 specifying chloramphenicol resistance. Mol Gen Genet. 1988 Aug;213(2-3):332–338. [PubMed]
  • Bender J, Kleckner N. Genetic evidence that Tn10 transposes by a nonreplicative mechanism. Cell. 1986 Jun 20;45(6):801–815. [PubMed]
  • Taylor RK, Manoil C, Mekalanos JJ. Broad-host-range vectors for delivery of TnphoA: use in genetic analysis of secreted virulence determinants of Vibrio cholerae. J Bacteriol. 1989 Apr;171(4):1870–1878. [PMC free article] [PubMed]
  • Gutierrez C, Barondess J, Manoil C, Beckwith J. The use of transposon TnphoA to detect genes for cell envelope proteins subject to a common regulatory stimulus. Analysis of osmotically regulated genes in Escherichia coli. J Mol Biol. 1987 May 20;195(2):289–297. [PubMed]
  • Way JC, Davis MA, Morisato D, Roberts DE, Kleckner N. New Tn10 derivatives for transposon mutagenesis and for construction of lacZ operon fusions by transposition. Gene. 1984 Dec;32(3):369–379. [PubMed]
  • Miller VL, Mekalanos JJ. A novel suicide vector and its use in construction of insertion mutations: osmoregulation of outer membrane proteins and virulence determinants in Vibrio cholerae requires toxR. J Bacteriol. 1988 Jun;170(6):2575–2583. [PMC free article] [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]
  • Lissner CR, Swanson RN, O'Brien AD. Genetic control of the innate resistance of mice to Salmonella typhimurium: expression of the Ity gene in peritoneal and splenic macrophages isolated in vitro. J Immunol. 1983 Dec;131(6):3006–3013. [PubMed]
  • Hoiseth SK, Stocker BA. Aromatic-dependent Salmonella typhimurium are non-virulent and effective as live vaccines. Nature. 1981 May 21;291(5812):238–239. [PubMed]
  • Stocker BA. Auxotrophic Salmonella typhi as live vaccine. Vaccine. 1988 Apr;6(2):141–145. [PubMed]
  • BACON GA, BURROWS TW, YATES M. The effects of biochemical mutation on the virulence of Bacterium typhosum; the loss of virulence of certain mutants. Br J Exp Pathol. 1951 Apr;32(2):85–96. [PMC free article] [PubMed]
  • Curtiss R, 3rd, Kelly SM. Salmonella typhimurium deletion mutants lacking adenylate cyclase and cyclic AMP receptor protein are avirulent and immunogenic. Infect Immun. 1987 Dec;55(12):3035–3043. [PMC free article] [PubMed]
  • Christman MF, Morgan RW, Jacobson FS, Ames BN. Positive control of a regulon for defenses against oxidative stress and some heat-shock proteins in Salmonella typhimurium. Cell. 1985 Jul;41(3):753–762. [PubMed]
  • Hirschman J, Wong PK, Sei K, Keener J, Kustu S. Products of nitrogen regulatory genes ntrA and ntrC of enteric bacteria activate glnA transcription in vitro: evidence that the ntrA product is a sigma factor. Proc Natl Acad Sci U S A. 1985 Nov;82(22):7525–7529. [PMC free article] [PubMed]
  • Nara F, Matsuyama S, Mizuno T, Mizushima S. Molecular analysis of mutant ompR genes exhibiting different phenotypes as to osmoregulation of the ompF and ompC genes of Escherichia coli. Mol Gen Genet. 1986 Feb;202(2):194–199. [PubMed]
  • Kier LD, Weppelman RM, Ames BN. Regulation of nonspecific acid phosphatase in Salmonella: phoN and phoP genes. J Bacteriol. 1979 Apr;138(1):155–161. [PMC free article] [PubMed]
  • Lipman DJ, Pearson WR. Rapid and sensitive protein similarity searches. Science. 1985 Mar 22;227(4693):1435–1441. [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]
  • Weppelman R, Kier LD, Ames BN. Properties of two phosphatases and a cyclic phosphodiesterase of Salmonella typhimurium. J Bacteriol. 1977 Apr;130(1):411–419. [PMC free article] [PubMed]
  • Kier LD, Weppelman R, Ames BN. Regulation of two phosphatases and a cyclic phosphodiesterase of Salmonella typhimurium. J Bacteriol. 1977 Apr;130(1):420–428. [PMC free article] [PubMed]
  • Makino K, Shinagawa H, Amemura M, Nakata A. Nucleotide sequence of the phoB gene, the positive regulatory gene for the phosphate regulon of Escherichia coli K-12. J Mol Biol. 1986 Jul 5;190(1):37–44. [PubMed]
  • Drury LS, Buxton RS. DNA sequence analysis of the dye gene of Escherichia coli reveals amino acid homology between the dye and OmpR proteins. J Biol Chem. 1985 Apr 10;260(7):4236–4242. [PubMed]
  • Amemura M, Makino K, Shinagawa H, Nakata A. Nucleotide sequence of the phoM region of Escherichia coli: four open reading frames may constitute an operon. J Bacteriol. 1986 Oct;168(1):294–302. [PMC free article] [PubMed]
  • Winans SC, Ebert PR, Stachel SE, Gordon MP, Nester EW. A gene essential for Agrobacterium virulence is homologous to a family of positive regulatory loci. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8278–8282. [PMC free article] [PubMed]
  • Miller VL, Taylor RK, Mekalanos JJ. Cholera toxin transcriptional activator toxR is a transmembrane DNA binding protein. Cell. 1987 Jan 30;48(2):271–279. [PubMed]
  • Mutoh N, Simon MI. Nucleotide sequence corresponding to five chemotaxis genes in Escherichia coli. J Bacteriol. 1986 Jan;165(1):161–166. [PMC free article] [PubMed]
  • Miranda-Ríos J, Sánchez-Pescador R, Urdea M, Covarrubias AA. The complete nucleotide sequence of the glnALG operon of Escherichia coli K12. Nucleic Acids Res. 1987 Mar 25;15(6):2757–2770. [PMC free article] [PubMed]
  • Weiss V, Magasanik B. Phosphorylation of nitrogen regulator I (NRI) of Escherichia coli. Proc Natl Acad Sci U S A. 1988 Dec;85(23):8919–8923. [PMC free article] [PubMed]
  • Hess JF, Bourret RB, Simon MI. Histidine phosphorylation and phosphoryl group transfer in bacterial chemotaxis. Nature. 1988 Nov 10;336(6195):139–143. [PubMed]
  • Ninfa AJ, Magasanik B. Covalent modification of the glnG product, NRI, by the glnL product, NRII, regulates the transcription of the glnALG operon in Escherichia coli. Proc Natl Acad Sci U S A. 1986 Aug;83(16):5909–5913. [PMC free article] [PubMed]
  • Engelman DM, Steitz TA, Goldman A. Identifying nonpolar transbilayer helices in amino acid sequences of membrane proteins. Annu Rev Biophys Biophys Chem. 1986;15:321–353. [PubMed]
  • Ganz T, Selsted ME, Szklarek D, Harwig SS, Daher K, Bainton DF, Lehrer RI. Defensins. Natural peptide antibiotics of human neutrophils. J Clin Invest. 1985 Oct;76(4):1427–1435. [PMC free article] [PubMed]

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