Biochemistry (Moscow)

, Volume 80, Issue 11, pp 1447–1456 | Cite as

Regulation of flagellar gene expression in Bacteria

  • I. A. Osterman
  • Yu. Yu. Dikhtyar
  • A. A. Bogdanov
  • O. A. Dontsova
  • P. V. SergievEmail author


The flagellum of a bacterium is a supramolecular structure of extreme complexity comprising simultaneously both a unique system of protein transport and a molecular machine that enables the bacterial cell movement. The cascade of expression of genes encoding flagellar components is closely coordinated with the steps of molecular machine assembly, constituting an amazing regulatory system. Data on structure, assembly, and regulation of flagellar gene expression are summarized in this review. The regulatory mechanisms and correlation of the process of regulation of gene expression and flagellum assembly known from the literature are described.


flagella motility bacteria molecular machine transcriptional control 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Patrick, J. E., and Kearns, D. B. (2012) Swarming motility and the control of master regulators of flagellar biosynthesis, Mol. Microbiol., 83, 14–23.PubMedCentralCrossRefPubMedGoogle Scholar
  2. 2.
    Macnab, R. M. (1996) Escherichia coli and Salmonella (Neidhardt, F. C., Curtiss, R. I., Ingraham, J. L., Lin, C. C., Low, K. B., Magasanik, B., Reznikoff, W. S., Riley, M., Schaechter, M., and Umbarger, H. E., eds.) American Society for Microbiology Press, Washington, D.C., pp. 123–145.Google Scholar
  3. 3.
    Chen, S., Beeby, M., Murphy, G. E., Leadbetter, J. R., Hendrixson, D. R., Briegel, A., Li, Z., Shi, J., Tocheva, E. I., Muller, A., Dobro, M. J., and Jensen, G. J. (2011) Structural diversity of bacterial flagellar motors, EMBO J., 30, 2972–2981.PubMedCentralCrossRefPubMedGoogle Scholar
  4. 4.
    Blair, D. F., and Berg, H. C. (1990) The MotA protein of E. coli is a proton-conducting component of the flagellar motor, Cell, 60, 439–449.CrossRefPubMedGoogle Scholar
  5. 5.
    Iino, T. (1969) Polarity of flagellar growth in salmonella, J. Gen. Microbiol., 56, 227–239.CrossRefPubMedGoogle Scholar
  6. 6.
    Jones, C. J., and Aizawa, S. (1991) The bacterial flagellum and flagellar motor: structure, assembly, and function, Adv. Microb. Physiol., 32, 109–172.CrossRefGoogle Scholar
  7. 7.
    Metlina, A. L. (2001) Prokaryotic flagella as biological motility system, Uspekhi Biol. Khim., 41, 229–282.Google Scholar
  8. 8.
    Blair, D. F. (2006) Fine structure of a fine machine, J. Bacteriol., 188, 7033–7035.PubMedCentralCrossRefPubMedGoogle Scholar
  9. 9.
    Berg, H. C. (2003) The rotary motor of bacterial flagella, Annu. Rev. Biochem., 72, 19–54.CrossRefPubMedGoogle Scholar
  10. 10.
    Chevance, F. F., and Hughes, K. T. (2008) Coordinating assembly of a bacterial macromolecular machine, Nat. Rev. Microbiol., 6, 455–465.CrossRefPubMedGoogle Scholar
  11. 11.
    Samatey, F. A., Matsunami, H., Imada, K., Nagashima, S., Shaikh, T. R., Thomas, D. R., Chen, J. Z., Derosier, D. J., Kitao, A., and Namba, K. (2004) Structure of the bacterial flagellar hook and implication for the molecular universal joint mechanism, Nature, 431, 1062–1068.CrossRefPubMedGoogle Scholar
  12. 12.
    Ikeda, T., Asakura, S., and Kamiya, R. (1989) Total reconstitution of Salmonella flagellar filaments from hook and purified flagellin and hook-associated proteins in vitro, J. Mol. Biol., 209, 109–114.CrossRefPubMedGoogle Scholar
  13. 13.
    Jones, C. J., Macnab, R. M., Okino, H., and Aizawa, S. (1990) Stoichiometric analysis of the flagellar hook-(basalbody) complex of Salmonella typhimurium, J. Mol. Biol., 212, 377–387.CrossRefPubMedGoogle Scholar
  14. 14.
    Hirano, T., Minamino, T., and Macnab, R. M. (2001) The role in flagellar rod assembly of the N-terminal domain of Salmonella FlgJ, a flagellum-specific muramidase, J. Mol. Biol., 312, 359–369.CrossRefPubMedGoogle Scholar
  15. 15.
    Imada, K., Vonderviszt, F., Furukawa, Y., Oosawa, K., and Namba, K. (1998) Assembly characteristics of flagellar cap protein HAP2 of Salmonella: decamer and pentamer in the pH-sensitive equilibrium, J. Mol. Biol., 277, 883–891.CrossRefPubMedGoogle Scholar
  16. 16.
    Ikeda, T., Kamiya, R., and Yamaguchi, S. (1983) Excretion of flagellin by a short-flagella mutant of Salmonella typhimurium, J. Bacteriol., 153, 506–510.PubMedCentralPubMedGoogle Scholar
  17. 17.
    Ferris, H. U., and Minamino, T. (2006) Flipping the switch: bringing order to flagellar assembly, Trends Microbiol., 14, 519–526.CrossRefPubMedGoogle Scholar
  18. 18.
    Akeda, Y., and Galan, J. E. (2005) Chaperone release and unfolding of substrates in type III secretion, Nature, 437, 911–915.CrossRefPubMedGoogle Scholar
  19. 19.
    Hirano, T., Minamino, T., Namba, K., and Macnab, R. M. (2003) Substrate specificity classes and the recognition signal for Salmonella type III flagellar export, J. Bacteriol., 185, 2485–2492.PubMedCentralCrossRefPubMedGoogle Scholar
  20. 20.
    Minamino, T., Doi, H., and Kutsukake, K. (1999) Substrate specificity switching of the flagellum-specific export apparatus during flagellar morphogenesis in Salmonella typhimurium, Biosci. Biotechnol. Biochem., 63, 1301–1303.CrossRefPubMedGoogle Scholar
  21. 21.
    Minamino, T., and Macnab, R. M. (2000) Domain structure of Salmonella FlhB, a flagellar export component responsible for substrate specificity switching, J. Bacteriol., 182, 4906–4914.PubMedCentralCrossRefPubMedGoogle Scholar
  22. 22.
    Fraser, G. M., Hirano, T., Ferris, H. U., Devgan, L. L., Kihara, M., and Macnab, R. M. (2003) Substrate specificity of type III flagellar protein export in Salmonella is controlled by subdomain interactions in FlhB, Mol. Microbiol., 48, 1043–1057.CrossRefPubMedGoogle Scholar
  23. 23.
    Patterson-Delafield, J., Martinez, R. J., Stocker, B. A., and Yamaguchi, S. (1973) A new fla gene in Salmonella typhimurium–flaR–and its mutant phenotype-superhooks, Arch. Microbiol., 90, 107–120.Google Scholar
  24. 24.
    Hirano, T., Yamaguchi, S., Oosawa, K., and Aizawa, S. (1994) Roles of FliK and FlhB in determination of flagellar hook length in Salmonella typhimurium, J. Bacteriol., 176, 5439–5449.PubMedCentralPubMedGoogle Scholar
  25. 25.
    Minamino, T., Saijo-Hamano, Y., Furukawa, Y., Gonzalez-Pedrajo, B., Macnab, R. M., and Namba, K. (2004) Domain organization and function of Salmonella FliK, a flagellar hook-length control protein, J. Mol. Biol., 341, 491–502.CrossRefPubMedGoogle Scholar
  26. 26.
    Minamino, T., Gonzalez-Pedrajo, B., Yamaguchi, K., Aizawa, S. I., and Macnab, R. M. (1999) FliK, the protein responsible for flagellar hook length control in Salmonella, is exported during hook assembly, Mol. Microbiol., 34, 295304.CrossRefGoogle Scholar
  27. 27.
    Journet, L., Agrain, C., Broz, P., and Cornelis, G. R. (2003) The needle length of bacterial injectisomes is determined by a molecular ruler, Science, 302, 1757–1760.CrossRefPubMedGoogle Scholar
  28. 28.
    Kubori, T., Shimamoto, N., Yamaguchi, S., Namba, K., and Aizawa, S. (1992) Morphological pathway of flagellar assembly in Salmonella typhimurium, J. Mol. Biol., 226, 433–446.CrossRefPubMedGoogle Scholar
  29. 29.
    Karlinsey, J. E., Tsui, H. C., Winkler, M. E., and Hughes, K. T. (1998) Flk couples flgM translation to flagellar ring assembly in Salmonella typhimurium, J. Bacteriol., 180, 5384–5397.PubMedCentralPubMedGoogle Scholar
  30. 30.
    Karlinsey, J. E., Pease, A. J., Winkler, M. E., Bailey, J. L., and Hughes, K. T. (1997) The flk gene of Salmonella typhimurium couples flagellar Pand L-ring assembly to flagellar morphogenesis, J. Bacteriol., 179, 2389–2400.PubMedCentralPubMedGoogle Scholar
  31. 31.
    Kutsukake, K. (1997) Hook-length control of the exportswitching machinery involves a double-locked gate in Salmonella typhimurium flagellar morphogenesis, J. Bacteriol., 179, 1268–1273.PubMedCentralPubMedGoogle Scholar
  32. 32.
    Aldridge, P., Karlinsey, J. E., Becker, E., Chevance, F. F., and Hughes, K. T. (2006) Flk prevents premature secretion of the anti-s factor FlgM into the periplasm, Mol. Microbiol., 60, 630–643.PubMedCentralCrossRefPubMedGoogle Scholar
  33. 33.
    Chevance, F. F., Takahashi, N., Karlinsey, J. E., Gnerer, J., Hirano, T., Samudrala, R., Aizawa, S., and Hughes, K. T. (2007) The mechanism of outer membrane penetration by the eubacterial flagellum and implications for spirochete evolution, Genes Dev., 21, 2326–2335.PubMedCentralCrossRefPubMedGoogle Scholar
  34. 34.
    Komeda, Y., Kutsukake, K., and Iino, T. (1980) Definition of additional flagellar genes in Escherichia coli K12, Genetics, 94, 277–290.PubMedCentralPubMedGoogle Scholar
  35. 35.
    Kutsukake, K., Ohya, Y., and Iino, T. (1990) Transcriptional analysis of the flagellar regulon of Salmonella typhimurium, J. Bacteriol., 172, 741–747.PubMedCentralPubMedGoogle Scholar
  36. 36.
    Wang, S., Fleming, R. T., Westbrook, E. M., Matsumura, P., and McKay, D. B. (2006) Structure of the Escherichia coli FlhDC complex, a prokaryotic heteromeric regulator of transcription, J. Mol. Biol., 355, 798–808.CrossRefPubMedGoogle Scholar
  37. 37.
    Keseler, I. M., Collado-Vides, J., Santos-Zavaleta, A., Peralta-Gil, M., Gama-Castro, S., Muniz-Rascado, L., Bonavides-Martinez, C., Paley, S., Krummenacker, M., Altman, T., Kaipa, P., Spaulding, A., Pacheco, J., Latendresse, M., Fulcher, C., Sarker, M., Shearer, A. G., Mackie, A., Paulsen, I., Gunsalus, R. P., and Karp, P. D. (2011) EcoCyc: a comprehensive database of Escherichia coli biology, Nucleic Acids Res., 39, 583–590.CrossRefGoogle Scholar
  38. 38.
    Chilcott, G. S., and Hughes, K. T. (2000) Coupling of flagellar gene expression to flagellar assembly in Salmonella enterica serovar typhimurium and Escherichia coli, Microbiol. Mol. Biol. Rev., 64, 694–708.PubMedCentralCrossRefPubMedGoogle Scholar
  39. 39.
    Liu, X., Fujita, N., Ishihama, A., and Matsumura, P. (1995) The C-terminal region of the alpha subunit of Escherichia coli RNA polymerase is required for transcriptional activation of the flagellar level II operons by the FlhD/FlhC complex, J. Bacteriol., 177, 5186–5188.PubMedCentralPubMedGoogle Scholar
  40. 40.
    Liu, X., and Matsumura, P. (1994) The FlhD/FlhC complex, a transcriptional activator of the Escherichia coli flagellar class II operons, J. Bacteriol., 176, 7345–7351.PubMedCentralPubMedGoogle Scholar
  41. 41.
    Pruss, B. M., Liu, X., Hendrickson, W., and Matsumura, P. (2001) FlhD/FlhC-regulated promoters analyzed by gene array and lacZ gene fusions, FEMS Microbiol. Lett., 197, 91–97.CrossRefPubMedGoogle Scholar
  42. 42.
    Adler, J., and Templeton, B. (1967) The effect of environmental conditions on the motility of Escherichia coli, J. Gen. Microbiol., 46, 175–184.CrossRefPubMedGoogle Scholar
  43. 43.
    De Crombrugghe, B., Busby, S., and Buc, H. (1984) Cyclic AMP receptor protein: role in transcription activation, Science, 224, 831–838.CrossRefPubMedGoogle Scholar
  44. 44.
    Soutourina, O., Kolb, A., Krin, E., Laurent-Winter, C., Rimsky, S., Danchin, A., and Bertin, P. (1999) Multiple control of flagellum biosynthesis in Escherichia coli: role of H-NS protein and the cyclic AMP-catabolite activator protein complex in transcription of the flhDC master operon, J. Bacteriol., 181, 7500–7508.PubMedCentralPubMedGoogle Scholar
  45. 45.
    Sperandio, V., Torres, A. G., Giron, J. A., and Kaper, J. B. (2001) Quorum sensing is a global regulatory mechanism in enterohemorrhagic Escherichia coli O157:H7, J. Bacteriol., 183, 5187–5197.PubMedCentralCrossRefPubMedGoogle Scholar
  46. 46.
    Sperandio, V., Torres, A. G., and Kaper, J. B. (2002) Quorum sensing Escherichia coli regulators B and C (QseBC): a novel two-component regulatory system involved in the regulation of flagella and motility by quorum sensing in E. coli, Mol. Microbiol., 43, 809–821.CrossRefPubMedGoogle Scholar
  47. 47.
    Lehti, T. A., Bauchart, P., Dobrindt, U., Korhonen, T. K., and Westerlund-Wikstrom, B. (2012) The fimbriae activator MatA switches off motility in Escherichia coli by repression of the flagellar master operon flhDC, Microbiology, 158, 1444–1455.CrossRefPubMedGoogle Scholar
  48. 48.
    Lehnen, D., Blumer, C., Polen, T., Wackwitz, B., Wendisch, V. F., and Unden, G. (2002) LrhA as a new transcriptional key regulator of flagella, motility and chemotaxis genes in Escherichia coli, Mol. Microbiol., 45, 521–532.CrossRefPubMedGoogle Scholar
  49. 49.
    Shin, S., and Park, C. (1995) Modulation of flagellar expression in Escherichia coli by acetyl phosphate and the osmoregulator OmpR, J. Bacteriol., 177, 4696–4702.PubMedCentralPubMedGoogle Scholar
  50. 50.
    Francez-Charlot, A., Laugel, B., Van Gemert, A., Dubarry, N., Wiorowski, F., Castanie-Cornet, M. P., Gutierrez, C., and Cam, K. (2003) RcsCDB His-Asp phosphorelay system negatively regulates the flhDC operon in Escherichia coli, Mol. Microbiol., 49, 823–832.CrossRefPubMedGoogle Scholar
  51. 51.
    Gottesman, S., Trisler, P., and Torres-Cabassa, A. (1985) Regulation of capsular polysaccharide synthesis in Escherichia coli K-12: characterization of three regulatory genes, J. Bacteriol., 162, 1111–1119.PubMedCentralPubMedGoogle Scholar
  52. 52.
    Lee, C., and Park, C. (2013) Mutations upregulating the flhDC operon of Escherichia coli K-12, J. Microbiol., 51, 140–144.CrossRefPubMedGoogle Scholar
  53. 53.
    Lemke, J. J., Durfee, T., and Gourse, R. L. (2009) DksA and ppGpp directly regulate transcription of the Escherichia coli flagellar cascade, Mol. Microbiol., 74, 13681379.Google Scholar
  54. 54.
    De Lay, N., and Gottesman, S. (2012) A complex network of small non-coding RNAs regulate motility in Escherichia coli, Mol. Microbiol., 86, 524–538.CrossRefPubMedGoogle Scholar
  55. 55.
    Thomason, M. K., Fontaine, F., De Lay, N., and Storz, G. (2012) A small RNA that regulates motility and biofilm formation in response to changes in nutrient availability in Escherichia coli, Mol. Microbiol., 84, 17–35.PubMedCentralCrossRefPubMedGoogle Scholar
  56. 56.
    Yakhnin, A. V., Baker, C. S., Vakulskas, C. A., Yakhnin, H., Berezin, I., Romeo, T., and Babitzke, P. (2013) CsrA activates flhDC expression by protecting flhDC mRNA from RNase E-mediated cleavage, Mol. Microbiol., 87, 851866.CrossRefGoogle Scholar
  57. 57.
    Kitagawa, R., Takaya, A., and Yamamoto, T. (2011) Dual regulatory pathways of flagellar gene expression by ClpXP protease in enterohaemorrhagic Escherichia coli, Microbiology, 157, 3094–3103.CrossRefPubMedGoogle Scholar
  58. 58.
    Shi, W., Zhou, Y., Wild, J., Adler, J., and Gross, C. A. (1992) DnaK, DnaJ, and GrpE are required for flagellum synthesis in Escherichia coli, J. Bacteriol., 174, 62566263.Google Scholar
  59. 59.
    Arnosti, D. N., and Chamberlin, M. J. (1989) Secondary s factor controls transcription of flagellar and chemotaxis genes in Escherichia coli, Proc. Natl. Acad. Sci. USA, 86, 830–834.PubMedCentralCrossRefPubMedGoogle Scholar
  60. 60.
    Ohnishi, K., Kutsukake, K., Suzuki, H., and Lino, T. (1992) A novel transcriptional regulation mechanism in the flagellar regulon of Salmonella typhimurium: an anti-s factor inhibits the activity of the flagellum-specific s factor, sF, Mol. Microbiol., 6, 3149–3157.CrossRefGoogle Scholar
  61. 61.
    Sorenson, M. K., Ray, S. S., and Darst, S. A. (2004) Crystal structure of the flagellar s/anti-s complex s28/FlgM reveals an intact s factor in an inactive conformation, Mol. Cell, 14, 127–138.CrossRefPubMedGoogle Scholar
  62. 62.
    Kutsukake, K. (1994) Excretion of the anti-s factor through a flagellar substructure couples flagellar gene expression with flagellar assembly in Salmonella typhimurium, Mol. Gen. Genet., 243, 605–612.PubMedGoogle Scholar
  63. 63.
    Hughes, K. T., Gillen, K. L., Semon, M. J., and Karlinsey, J. E. (1993) Sensing structural intermediates in bacterial flagellar assembly by export of a negative regulator, Science, 262, 1277–1280.CrossRefPubMedGoogle Scholar
  64. 64.
    Zaslaver, A., Mayo, A. E., Rosenberg, R., Bashkin, P., Sberro, H., Tsalyuk, M., Surette, M. G., and Alon, U. (2004) Just-in-time transcription program in metabolic pathways, Nat. Genet., 36, 486–491.CrossRefPubMedGoogle Scholar
  65. 65.
    Hollands, K., Lee, D. J., Lloyd, G. S., and Busby, S. J. (2010) Activation of s28-dependent transcription in Escherichia coli by the cyclic AMP receptor protein requires an unusual promoter organization, Mol. Microbiol., 75, 1098–1111.PubMedCentralCrossRefPubMedGoogle Scholar
  66. 66.
    Kundu, T. K., Kusano, S., and Ishihama, A. (1997) Promoter selectivity of Escherichia coli RNA polymerase sF holoenzyme involved in transcription of flagellar and chemotaxis genes, J. Bacteriol., 179, 4264–4269.PubMedCentralPubMedGoogle Scholar
  67. 67.
    Zhao, K., Liu, M., and Burgess, R. R. (2007) Adaptation in bacterial flagellar and motility systems: from regulon members to “foraging”-like behavior in E. coli, Nucleic Acids Res., 35, 4441–4452.PubMedCentralCrossRefPubMedGoogle Scholar
  68. 68.
    Brutinel, E. D., and Yahr, T. L. (2008) Control of gene expression by type III secretory activity, Curr. Opin. Microbiol., 11, 128–133.PubMedCentralCrossRefPubMedGoogle Scholar
  69. 69.
    Kutsukake, K., Ikebe, T., and Yamamoto, S. (1999) Two novel regulatory genes, fliT and fliZ, in the flagellar regulon of Salmonella, Genes Genet. Syst., 74, 287–292.CrossRefPubMedGoogle Scholar
  70. 70.
    Aldridge, C., Poonchareon, K., Saini, S., Ewen, T., Soloyva, A., Rao, C. V., Imada, K., Minamino, T., and Aldridge, P. D. (2010) The interaction dynamics of a negative feedback loop regulates flagellar number in Salmonella enterica serovar Typhimurium, Mol. Microbiol., 78, 1416–1430.CrossRefPubMedGoogle Scholar
  71. 71.
    Yamamoto, S., and Kutsukake, K. (2006) FliT acts as an anti-FlhD2C2 factor in the transcriptional control of the flagellar regulon in Salmonella enterica serovar typhimurium, J. Bacteriol., 188, 6703–6708.PubMedCentralCrossRefPubMedGoogle Scholar
  72. 72.
    Bennett, J. C., Thomas, J., Fraser, G. M., and Hughes, C. (2001) Substrate complexes and domain organization of the Salmonella flagellar export chaperones FlgN and FliT, Mol. Microbiol., 39, 781–791.PubMedCentralCrossRefPubMedGoogle Scholar
  73. 73.
    Aldridge, P. D., Karlinsey, J. E., Aldridge, C., Birchall, C., Thompson, D., Yagasaki, J., and Hughes, K. T. (2006) The flagellar-specific transcription factor, s28, is the type III secretion chaperone for the flagellar-specific anti-s28 factor FlgM, Genes Dev., 20, 2315–2326.PubMedCentralCrossRefPubMedGoogle Scholar
  74. 74.
    Kutsukake, K., Okada, T., Yokoseki, T., and Iino, T. (1994) Sequence analysis of the flgA gene and its adjacent region in Salmonella typhimurium, and identification of another flagellar gene, flgN, Gene, 143, 49–54.CrossRefPubMedGoogle Scholar
  75. 75.
    Karlinsey, J. E., Lonner, J., Brown, K. L., and Hughes, K. T. (2000) Translation/secretion coupling by type III secretion systems, Cell, 102, 487–497.CrossRefPubMedGoogle Scholar
  76. 76.
    Aldridge, P., Gnerer, J., Karlinsey, J. E., and Hughes, K. T. (2006) Transcriptional and translational control of the Salmonella fliC gene, J. Bacteriol., 188, 4487–4496.PubMedCentralCrossRefPubMedGoogle Scholar
  77. 77.
    Rosu, V., Chevance, F. F., Karlinsey, J. E., Hirano, T., and Hughes, K. T. (2006) Translation inhibition of the Salmonella fliC gene by the fliC 5'-untranslated region, fliC coding sequences, and FlgM, J. Bacteriol., 188, 44974507.Google Scholar

Copyright information

© Pleiades Publishing, Ltd. 2015

Authors and Affiliations

  • I. A. Osterman
    • 1
  • Yu. Yu. Dikhtyar
    • 1
  • A. A. Bogdanov
    • 2
  • O. A. Dontsova
    • 1
    • 2
  • P. V. Sergiev
    • 1
    Email author
  1. 1.Faculty of ChemistryLomonosov Moscow State UniversityMoscowRussia
  2. 2.Belozersky Institute of Physico-Chemical BiologyLomonosov Moscow State UniversityMoscowRussia

Personalised recommendations