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J Bacteriol. 1995 Apr; 177(8): 2021–2032.
PMCID: PMC176845

Sequence, regulation, and functions of fis in Salmonella typhimurium.


The fis operon from Salmonella typhimurium has been cloned and sequenced, and the properties of Fis-deficient and Fis-constitutive strains were examined. The overall fis operon organization in S. typhimurium is the same as that in Escherichia coli, with the deduced Fis amino acid sequences being identical between both species. While the open reading frames upstream of fis have diverged slightly, the promoter regions between the two species are also identical between -49 and +94. Fis protein and mRNA levels fluctuated dramatically during the course of growth in batch cultures, peaking at approximately 40,000 dimers per cell in early exponential phase, and were undetectable after growth in stationary phase. fis autoregulation was less effective in S. typhimurium than that in E. coli, which can be correlated with the absence or reduced affinity of several Fis-binding sites in the S. typhimurium fis promoter region. Phenotypes of fis mutants include loss of Hin-mediated DNA inversion, cell filamentation, reduced growth rates in rich medium, and increased lag times when the mutants are subcultured after prolonged growth in stationary phase. On the other hand, cells constitutively expressing Fis exhibited normal logarithmic growth but showed a sharp reduction in survival during stationary phase. During the course of these studies, the sigma 28-dependent promoter within the hin-invertible segment that is responsible for fljB (H2) flagellin synthesis was precisely located.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Antón DN. Genetic control of defective cell shape and osmotic-sensitivity in a mutant of Salmonella typhimurium. Mol Gen Genet. 1978 Apr 17;160(3):277–286. [PubMed]
  • Ball CA, Johnson RC. Efficient excision of phage lambda from the Escherichia coli chromosome requires the Fis protein. J Bacteriol. 1991 Jul;173(13):4027–4031. [PMC free article] [PubMed]
  • Ball CA, Johnson RC. Multiple effects of Fis on integration and the control of lysogeny in phage lambda. J Bacteriol. 1991 Jul;173(13):4032–4038. [PMC free article] [PubMed]
  • Ball CA, Osuna R, Ferguson KC, Johnson RC. Dramatic changes in Fis levels upon nutrient upshift in Escherichia coli. J Bacteriol. 1992 Dec;174(24):8043–8056. [PMC free article] [PubMed]
  • Bétermier M, Lefrère V, Koch C, Alazard R, Chandler M. The Escherichia coli protein, Fis: specific binding to the ends of phage Mu DNA and modulation of phage growth. Mol Microbiol. 1989 Apr;3(4):459–468. [PubMed]
  • Bétermier M, Poquet I, Alazard R, Chandler M. Involvement of Escherichia coli FIS protein in maintenance of bacteriophage mu lysogeny by the repressor: control of early transcription and inhibition of transposition. J Bacteriol. 1993 Jun;175(12):3798–3811. [PMC free article] [PubMed]
  • Case CC, Roels SM, González JE, Simons EL, Simons RW. Analysis of the promoters and transcripts involved in IS10 anti-sense RNA control. Gene. 1988 Dec 10;72(1-2):219–236. [PubMed]
  • Craig NL. The mechanism of conservative site-specific recombination. Annu Rev Genet. 1988;22:77–105. [PubMed]
  • Dorgai L, Oberto J, Weisberg RA. Xis and Fis proteins prevent site-specific DNA inversion in lysogens of phage HK022. J Bacteriol. 1993 Feb;175(3):693–700. [PMC free article] [PubMed]
  • Filutowicz M, Ross W, Wild J, Gourse RL. Involvement of Fis protein in replication of the Escherichia coli chromosome. J Bacteriol. 1992 Jan;174(2):398–407. [PMC free article] [PubMed]
  • Finkel SE, Johnson RC. The Fis protein: it's not just for DNA inversion anymore. Mol Microbiol. 1992 Nov;6(22):3257–3265. [PubMed]
  • Foster-Hartnett D, Cullen PJ, Gabbert KK, Kranz RG. Sequence, genetic, and lacZ fusion analyses of a nifR3-ntrB-ntrC operon in Rhodobacter capsulatus. Mol Microbiol. 1993 May;8(5):903–914. [PubMed]
  • Foster-Hartnett D, Kranz RG. Analysis of the promoters and upstream sequences of nifA1 and nifA2 in Rhodobacter capsulatus; activation requires ntrC but not rpoN. Mol Microbiol. 1992 Apr;6(8):1049–1060. [PubMed]
  • Gille H, Egan JB, Roth A, Messer W. The FIS protein binds and bends the origin of chromosomal DNA replication, oriC, of Escherichia coli. Nucleic Acids Res. 1991 Aug 11;19(15):4167–4172. [PMC free article] [PubMed]
  • Gillen KL, Hughes KT. Negative regulatory loci coupling flagellin synthesis to flagellar assembly in Salmonella typhimurium. J Bacteriol. 1991 Apr;173(7):2301–2310. [PMC free article] [PubMed]
  • Gillen KL, Hughes KT. Transcription from two promoters and autoregulation contribute to the control of expression of the Salmonella typhimurium flagellar regulatory gene flgM. J Bacteriol. 1993 Nov;175(21):7006–7015. [PMC free article] [PubMed]
  • Gosink KK, Ross W, Leirmo S, Osuna R, Finkel SE, Johnson RC, Gourse RL. DNA binding and bending are necessary but not sufficient for Fis-dependent activation of rrnB P1. J Bacteriol. 1993 Mar;175(6):1580–1589. [PMC free article] [PubMed]
  • Haffter P, Bickle TA. Purification and DNA-binding properties of FIS and Cin, two proteins required for the bacteriophage P1 site-specific recombination system, cin. J Mol Biol. 1987 Dec 20;198(4):579–587. [PubMed]
  • Hartz D, McPheeters DS, Traut R, Gold L. Extension inhibition analysis of translation initiation complexes. Methods Enzymol. 1988;164:419–425. [PubMed]
  • Hübner P, Arber W. Mutational analysis of a prokaryotic recombinational enhancer element with two functions. EMBO J. 1989 Feb;8(2):577–585. [PMC free article] [PubMed]
  • Johnson RC. Mechanism of site-specific DNA inversion in bacteria. Curr Opin Genet Dev. 1991 Oct;1(3):404–411. [PubMed]
  • Johnson RC, Ball CA, Pfeffer D, Simon MI. Isolation of the gene encoding the Hin recombinational enhancer binding protein. Proc Natl Acad Sci U S A. 1988 May;85(10):3484–3488. [PMC free article] [PubMed]
  • Johnson RC, Bruist MF, Simon MI. Host protein requirements for in vitro site-specific DNA inversion. Cell. 1986 Aug 15;46(4):531–539. [PubMed]
  • Koch C, Kahmann R. Purification and properties of the Escherichia coli host factor required for inversion of the G segment in bacteriophage Mu. J Biol Chem. 1986 Nov 25;261(33):15673–15678. [PubMed]
  • Koch C, Ninnemann O, Fuss H, Kahmann R. The N-terminal part of the E.coli DNA binding protein FIS is essential for stimulating site-specific DNA inversion but is not required for specific DNA binding. Nucleic Acids Res. 1991 Nov 11;19(21):5915–5922. [PMC free article] [PubMed]
  • Koch C, Vandekerckhove J, Kahmann R. Escherichia coli host factor for site-specific DNA inversion: cloning and characterization of the fis gene. Proc Natl Acad Sci U S A. 1988 Jun;85(12):4237–4241. [PMC free article] [PubMed]
  • Kolter R, Siegele DA, Tormo A. The stationary phase of the bacterial life cycle. Annu Rev Microbiol. 1993;47:855–874. [PubMed]
  • Kostrewa D, Granzin J, Koch C, Choe HW, Raghunathan S, Wolf W, Labahn J, Kahmann R, Saenger W. Three-dimensional structure of the E. coli DNA-binding protein FIS. Nature. 1991 Jan 10;349(6305):178–180. [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]
  • Kutsukake K, Iino T. Role of the FliA-FlgM regulatory system on the transcriptional control of the flagellar regulon and flagellar formation in Salmonella typhimurium. J Bacteriol. 1994 Jun;176(12):3598–3605. [PMC free article] [PubMed]
  • Landy A. Dynamic, structural, and regulatory aspects of lambda site-specific recombination. Annu Rev Biochem. 1989;58:913–949. [PubMed]
  • Lazarus LR, Travers AA. The Escherichia coli FIS protein is not required for the activation of tyrT transcription on entry into exponential growth. EMBO J. 1993 Jun;12(6):2483–2494. [PMC free article] [PubMed]
  • Little JW, Mount DW. The SOS regulatory system of Escherichia coli. Cell. 1982 May;29(1):11–22. [PubMed]
  • Maruyama T, Gojobori T, Aota S, Ikemura T. Codon usage tabulated from the GenBank genetic sequence data. Nucleic Acids Res. 1986;14 (Suppl):r151–r197. [PMC free article] [PubMed]
  • Maxam AM, Gilbert W. A new method for sequencing DNA. Proc Natl Acad Sci U S A. 1977 Feb;74(2):560–564. [PMC free article] [PubMed]
  • Nilsson L, Vanet A, Vijgenboom E, Bosch L. The role of FIS in trans activation of stable RNA operons of E. coli. EMBO J. 1990 Mar;9(3):727–734. [PMC free article] [PubMed]
  • Nilsson L, Verbeek H, Hoffmann U, Haupt M, Bosch L. Inactivation of the fis gene leads to reduced growth rate. FEMS Microbiol Lett. 1992 Nov 15;78(1):85–88. [PubMed]
  • Nilsson L, Verbeek H, Vijgenboom E, van Drunen C, Vanet A, Bosch L. FIS-dependent trans activation of stable RNA operons of Escherichia coli under various growth conditions. J Bacteriol. 1992 Feb;174(3):921–929. [PMC free article] [PubMed]
  • Ninnemann O, Koch C, Kahmann R. The E.coli fis promoter is subject to stringent control and autoregulation. EMBO J. 1992 Mar;11(3):1075–1083. [PMC free article] [PubMed]
  • North AK, Klose KE, Stedman KM, Kustu S. Prokaryotic enhancer-binding proteins reflect eukaryote-like modularity: the puzzle of nitrogen regulatory protein C. J Bacteriol. 1993 Jul;175(14):4267–4273. [PMC free article] [PubMed]
  • Numrych TE, Gumport RI, Gardner JF. A genetic analysis of Xis and FIS interactions with their binding sites in bacteriophage lambda. J Bacteriol. 1991 Oct;173(19):5954–5963. [PMC free article] [PubMed]
  • Ohnishi K, Kutsukake K, Suzuki H, Iino T. Gene fliA encodes an alternative sigma factor specific for flagellar operons in Salmonella typhimurium. Mol Gen Genet. 1990 Apr;221(2):139–147. [PubMed]
  • Osuna R, Finkel SE, Johnson RC. Identification of two functional regions in Fis: the N-terminus is required to promote Hin-mediated DNA inversion but not lambda excision. EMBO J. 1991 Jun;10(6):1593–1603. [PMC free article] [PubMed]
  • Pan CQ, Feng JA, Finkel SE, Landgraf R, Sigman D, Johnson RC. Structure of the Escherichia coli Fis-DNA complex probed by protein conjugated with 1,10-phenanthroline copper(I) complex. Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1721–1725. [PMC free article] [PubMed]
  • Ross W, Thompson JF, Newlands JT, Gourse RL. E.coli Fis protein activates ribosomal RNA transcription in vitro and in vivo. EMBO J. 1990 Nov;9(11):3733–3742. [PMC free article] [PubMed]
  • Sanderson KE, Roth JR. Linkage map of Salmonella typhimurium, Edition VI. Microbiol Rev. 1983 Sep;47(3):410–453. [PMC free article] [PubMed]
  • Silverman M, Zieg J, Simon M. Flagellar-phase variation: isolation of the rh1 gene. J Bacteriol. 1979 Jan;137(1):517–523. [PMC free article] [PubMed]
  • Slany RK, Kersten H. The promoter of the tgt/sec operon in Escherichia coli is preceded by an upstream activation sequence that contains a high affinity FIS binding site. Nucleic Acids Res. 1992 Aug 25;20(16):4193–4198. [PMC free article] [PubMed]
  • Thompson JF, Moitoso de Vargas L, Koch C, Kahmann R, Landy A. Cellular factors couple recombination with growth phase: characterization of a new component in the lambda site-specific recombination pathway. Cell. 1987 Sep 11;50(6):901–908. [PubMed]
  • Tormo A, Almirón M, Kolter R. surA, an Escherichia coli gene essential for survival in stationary phase. J Bacteriol. 1990 Aug;172(8):4339–4347. [PMC free article] [PubMed]
  • Walker GC. Mutagenesis and inducible responses to deoxyribonucleic acid damage in Escherichia coli. Microbiol Rev. 1984 Mar;48(1):60–93. [PMC free article] [PubMed]
  • Weinreich MD, Reznikoff WS. Fis plays a role in Tn5 and IS50 transposition. J Bacteriol. 1992 Jul;174(14):4530–4537. [PMC free article] [PubMed]
  • Xu J, Johnson RC. Identification of genes negatively regulated by Fis: Fis and RpoS comodulate growth-phase-dependent gene expression in Escherichia coli. J Bacteriol. 1995 Feb;177(4):938–947. [PMC free article] [PubMed]
  • Youderian P, Sugiono P, Brewer KL, Higgins NP, Elliott T. Packaging specific segments of the Salmonella chromosome with locked-in Mud-P22 prophages. Genetics. 1988 Apr;118(4):581–592. [PMC free article] [PubMed]
  • Yuan HS, Finkel SE, Feng JA, Kaczor-Grzeskowiak M, Johnson RC, Dickerson RE. The molecular structure of wild-type and a mutant Fis protein: relationship between mutational changes and recombinational enhancer function or DNA binding. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9558–9562. [PMC free article] [PubMed]
  • Zieg J, Silverman M, Hilmen M, Simon M. Recombinational switch for gene expression. Science. 1977 Apr 8;196(4286):170–172. [PubMed]
  • Zieg J, Hilmen M, Simon M. Regulation of gene expression by site-specific inversion. Cell. 1978 Sep;15(1):237–244. [PubMed]
  • Zieg J, Simon M. Analysis of the nucleotide sequence of an invertible controlling element. Proc Natl Acad Sci U S A. 1980 Jul;77(7):4196–4200. [PMC free article] [PubMed]

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