Gene Symbol: flhD
Description: flagellar class II regulon transcriptional activator, with FlhC
Alias: ECK1893, JW1881, flbB
Species: Escherichia coli str. K-12 substr. MG1655

Top Publications

  1. Liu X, Fujita N, Ishihama A, Matsumura P. 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. 1995;177:5186-8 pubmed
    ..In this report, we demonstrate that the FlhD/FlhC complex, a transcription activator of the Escherichia coli flagellar regulon, requires the C-terminal domain ..
  2. Prüss B, Campbell J, Van Dyk T, Zhu C, Kogan Y, Matsumura P. FlhD/FlhC is a regulator of anaerobic respiration and the Entner-Doudoroff pathway through induction of the methyl-accepting chemotaxis protein Aer. J Bacteriol. 2003;185:534-43 pubmed
    The regulation by two transcriptional activators of flagellar expression (FlhD and FlhC) and the chemotaxis methyl-accepting protein Aer was studied with glass slide DNA microarrays...
  3. Sperandio V, Torres A, Kaper J. 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. 2002;43:809-21 pubmed
    ..Transcription of flhD, fliA, motA and fliC::lacZ fusions was decreased in the qseC mutant, suggesting that qseBC is a transcriptional ..
  4. Yakhnin A, Baker C, Vakulskas C, Yakhnin H, Berezin I, Romeo T, et al. CsrA activates flhDC expression by protecting flhDC mRNA from RNase E-mediated cleavage. Mol Microbiol. 2013;87:851-66 pubmed publisher
    ..b>flhD'-'lacZ expression was reduced by mutations in csrA and/or the CsrA binding sites...
  5. Campos A, Zhang R, Alkire R, Matsumura P, Westbrook E. Crystal structure of the global regulator FlhD from Escherichia coli at 1.8 A resolution. Mol Microbiol. 2001;39:567-80 pubmed
    b>FlhD is a 13.3 kDa transcriptional activator protein of flagellar genes and a global regulator. FlhD activates the transcription of class II operons in the flagellar regulon when complexed with a second protein FlhC (21.5 kDa)...
  6. Yamamoto S, Kutsukake K. FliT acts as an anti-FlhD2C2 factor in the transcriptional control of the flagellar regulon in Salmonella enterica serovar typhimurium. J Bacteriol. 2006;188:6703-8 pubmed publisher
    ..The class 1 gene products FlhD and FlhC act together in an FlhD(2)C(2) heterotetramer, which binds upstream of the class 2 promoters to facilitate ..
  7. Shin S, Park C. Modulation of flagellar expression in Escherichia coli by acetyl phosphate and the osmoregulator OmpR. J Bacteriol. 1995;177:4696-702 pubmed
    ..Therefore, we propose that the phosphorylated OmpR, generated by either osmolarity change or the internal level of acetyl phosphate, negatively regulates the expression of flagella. ..
  8. Francez Charlot A, Laugel B, Van Gemert A, Dubarry N, Wiorowski F, Castanie Cornet M, et al. RcsCDB His-Asp phosphorelay system negatively regulates the flhDC operon in Escherichia coli. Mol Microbiol. 2003;49:823-32 pubmed
    ..The binding of RcsB and RcsA to this site was demonstrated by gel retardation and DNase I protection assays. In addition, mutation analysis suggests that RcsA-specific determinants lie in the right part of the 'RcsAB box'. ..
  9. Prüss B, Matsumura P. A regulator of the flagellar regulon of Escherichia coli, flhD, also affects cell division. J Bacteriol. 1996;178:668-74 pubmed
    The role of an activator of flagellar transcription in Escherichia coli, flhD, was investigated in the regulation of cell division...

More Information


  1. Soutourina O, Kolb A, Krin E, Laurent Winter C, Rimsky S, Danchin A, et al. 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. 1999;181:7500-8 pubmed
  2. Barker C, Prüss B, Matsumura P. Increased motility of Escherichia coli by insertion sequence element integration into the regulatory region of the flhD operon. J Bacteriol. 2004;186:7529-37 pubmed
    The flhD operon is the master operon of the flagellar regulon and a global regulator of metabolism...
  3. Stafford G, Ogi T, Hughes C. Binding and transcriptional activation of non-flagellar genes by the Escherichia coli flagellar master regulator FlhD2C2. Microbiology. 2005;151:1779-88 pubmed
    ..of Escherichia coli and other enterobacteria is controlled by the heterotetrameric master transcriptional regulator FlhD(2)C(2)...
  4. Wei B, Brun Zinkernagel A, Simecka J, Prüss B, Babitzke P, Romeo T. Positive regulation of motility and flhDC expression by the RNA-binding protein CsrA of Escherichia coli. Mol Microbiol. 2001;40:245-56 pubmed
    ..Thus, CsrA stimulates flhDC gene expression by a post-transcriptional mechanism reminiscent of its function in the repression of glycogen biosynthesis. ..
  5. Chilcott G, Hughes K. Coupling of flagellar gene expression to flagellar assembly in Salmonella enterica serovar typhimurium and Escherichia coli. Microbiol Mol Biol Rev. 2000;64:694-708 pubmed
    ..Cell cycle control and flagellar development are codependent. We discuss how all these levels of regulation ensure efficient assembly of the flagellum in response to environmental stimuli. ..
  6. Campos A, Matsumura P. Extensive alanine scanning reveals protein-protein and protein-DNA interaction surfaces in the global regulator FlhD from Escherichia coli. Mol Microbiol. 2001;39:581-94 pubmed
    b>FlhD and FlhC are the transcriptional activators of the flagellar regulon. The heterotetrameric complex formed by these two proteins activates the transcription of the class II flagellar genes...
  7. Prüss B, Liu X, Hendrickson W, Matsumura P. FlhD/FlhC-regulated promoters analyzed by gene array and lacZ gene fusions. FEMS Microbiol Lett. 2001;197:91-7 pubmed
    The Escherichia coli transcriptional regulatory complex FlhD/FlhC, initially identified as a flagella-specific activator, is a global regulator involved in many cellular processes...
  8. Lehnen D, Blumer C, Polen T, Wackwitz B, Wendisch V, Unden G. LrhA as a new transcriptional key regulator of flagella, motility and chemotaxis genes in Escherichia coli. Mol Microbiol. 2002;45:521-32 pubmed
    ..In gel retardation experiments, the LrhA protein bound specifically to flhD and lrhA promoter DNA (apparent K(D) approximately 20 nM), whereas the promoters of fliC, fliA and trg were not ..
  9. Claret L, Hughes C. Interaction of the atypical prokaryotic transcription activator FlhD2C2 with early promoters of the flagellar gene hierarchy. J Mol Biol. 2002;321:185-99 pubmed
    ..FlhC subunit can bind DNA independently, but the specificity and stability of the interaction is strengthened by FlhD. Here, photo-crosslinking established that both FlhC and the stabilising FlhD contact the DNA within the FlhD2C2 ..
  10. Wang X, Wood T. IS5 inserts upstream of the master motility operon flhDC in a quasi-Lamarckian way. ISME J. 2011;5:1517-25 pubmed publisher
    ..IS5 inserts upstream of flhD(+) when cells are grown on soft-agar plates that permit swimming motility, but does not insert upstream of this ..
  11. Wang S, Fleming R, Westbrook E, Matsumura P, McKay D. Structure of the Escherichia coli FlhDC complex, a prokaryotic heteromeric regulator of transcription. J Mol Biol. 2006;355:798-808 pubmed
    The hetero-oligomeric complex of the FlhD and FlhC proteins (FlhDC) regulates transcription from several flagellar and non-flagellar operons in bacteria...
  12. Leatham M, Stevenson S, Gauger E, Krogfelt K, Lins J, Haddock T, et al. Mouse intestine selects nonmotile flhDC mutants of Escherichia coli MG1655 with increased colonizing ability and better utilization of carbon sources. Infect Immun. 2005;73:8039-49 pubmed
    ..e., they grow better than their respective parents on sugars as sole carbon sources and are better colonizers of the mouse intestine. ..
  13. Lee C, Park C. Mutations upregulating the flhDC operon of Escherichia coli K-12. J Microbiol. 2013;51:140-4 pubmed publisher
    ..In this study, it was found that effects of the cis- and trans-acting mutations were acting in parallel, suggesting their apparently independent regulation of flagellar expression. ..
  14. Liu X, Matsumura P. The FlhD/FlhC complex, a transcriptional activator of the Escherichia coli flagellar class II operons. J Bacteriol. 1994;176:7345-51 pubmed
    The Escherichia coli flhD operon encodes two genes, flhD and flhC. Both gene products were overproduced and purified. The purified proteins formed a complex consisting of two FlhD and two FlhC molecules...
  15. Siegele D, Bain S, Mao W. Mutations in the flhD gene of Escherichia coli K-12 do not cause the reported effect on cell division. FEMS Microbiol Lett. 2010;309:94-9 pubmed publisher
    The hetero-oligomeric FlhD/FlhC complex is a global regulator of transcription in Escherichia coli. FlhD alone, independent of FlhC, has also been reported to control when E. coli cells stop dividing and enter the stationary phase...
  16. Soutourina O, Bertin P. Regulation cascade of flagellar expression in Gram-negative bacteria. FEMS Microbiol Rev. 2003;27:505-23 pubmed
    ..The remarkable parallelism in the functional organisation of flagellar systems suggests an evolutionary conservation of regulatory mechanisms in Gram-negative bacteria. ..
  17. Kalir S, Alon U. Using a quantitative blueprint to reprogram the dynamics of the flagella gene network. Cell. 2004;117:713-20 pubmed
    ..The present approach can be used to define blueprints of other gene networks and to quantitatively reprogram their dynamics. ..
  18. Uchiyama J, Nobue Y, Zhao H, Matsuzaki H, Nagahama H, Matsuoka S, et al. Involvement of sigmaS accumulation in repression of the flhDC operon in acidic phospholipid-deficient mutants of Escherichia coli. Microbiology. 2010;156:1650-60 pubmed publisher
    ..to shed light on this mechanism we isolated genes which, when supplied in multicopy, suppress the repression of flhD, and found that three genes, gadW, metE and yeaB, were capable of suppression...
  19. Fitzgerald D, Bonocora R, Wade J. Comprehensive mapping of the Escherichia coli flagellar regulatory network. PLoS Genet. 2014;10:e1004649 pubmed publisher
    ..Together, our data redefine the E. coli flagellar regulatory network, and provide new insight into the temporal orchestration of gene expression that coordinates the flagellar assembly process. ..
  20. Wood T, Gonzalez Barrios A, Herzberg M, Lee J. Motility influences biofilm architecture in Escherichia coli. Appl Microbiol Biotechnol. 2006;72:361-7 pubmed
    ..The differences in motility were due to differences in expression of the motility loci qseB, flhD, fliA, fliC, and motA (e.g...
  21. Hobman J, Patel M, Hidalgo Arroyo G, Cariss S, Avison M, Penn C, et al. Comparative genomic hybridization detects secondary chromosomal deletions in Escherichia coli K-12 MG1655 mutants and highlights instability in the flhDC region. J Bacteriol. 2007;189:8786-92 pubmed
  22. Sule P, Wadhawan T, Carr N, Horne S, Wolfe A, Prüss B. A combination of assays reveals biomass differences in biofilms formed by Escherichia coli mutants. Lett Appl Microbiol. 2009;49:299-304 pubmed publisher
    ..The ATP assay, in combination with other quantitative and qualitative assays, will allow us to perform genetic studies on the regulatory network that underlies the early steps in E. coli biofilm formation. ..
  23. Lemke J, Durfee T, Gourse R. DksA and ppGpp directly regulate transcription of the Escherichia coli flagellar cascade. Mol Microbiol. 2009;74:1368-79 pubmed publisher
  24. Ikebe T, Iyoda S, Kutsukake K. Promoter analysis of the class 2 flagellar operons of Salmonella. Genes Genet Syst. 1999;74:179-83 pubmed
    ..Expression of the class 2 operons requires the class 1 gene products, FlhD and FlhC, and is enhanced by an unknown mechanism in the presence of the class 3-specific sigma factor, FliA, and ..
  25. Gauger E, Leatham M, Mercado Lubo R, Laux D, Conway T, Cohen P. Role of motility and the flhDC Operon in Escherichia coli MG1655 colonization of the mouse intestine. Infect Immun. 2007;75:3315-24 pubmed
    ..within the regulatory region of the flhDC operon, which encodes the master regulator of flagellum biosynthesis, FlhD(4)C(2). Here we show that during intestinal colonization by wild-type E...
  26. Zhang Z, Kukita C, Humayun M, Saier M. Environment-directed activation of the Escherichia coliflhDC operon by transposons. Microbiology. 2017;163:554-569 pubmed publisher
  27. Bartlett D, Frantz B, Matsumura P. Flagellar transcriptional activators FlbB and FlaI: gene sequences and 5' consensus sequences of operons under FlbB and FlaI control. J Bacteriol. 1988;170:1575-81 pubmed
    ..Iino, Annu. Rev. Genet. 11:161-182, 1977; Y. Komeda, J. Bacteriol. 168: 1315-1318). The master operon, flbB, has been sequenced, and one of its gene products (FlaI) has been identified...
  28. Mizushima T, Koyanagi R, Suzuki E, Tomura A, Kutsukake K, Miki T, et al. Control by phosphatidylglycerol of expression of the flhD gene in Escherichia coli. Biochim Biophys Acta. 1995;1245:397-401 pubmed
    ..FEBS Letters 329, 287-290, 1993). We now describe evidence for a decrease in promoter activity of the flhD gene, a master gene for flagellum synthesis, in the pgsA3 mutant...
  29. Herrgard M, Palsson B. Flagellar biosynthesis in silico: building quantitative models of regulatory networks. Cell. 2004;117:689-90 pubmed
    ..The work by provides a general approach for building detailed models of transcriptional regulatory networks. ..
  30. Horne S, Mattson K, Prüss B. An Escherichia coli aer mutant exhibits a reduced ability to colonize the streptomycin-treated mouse large intestine. Antonie Van Leeuwenhoek. 2009;95:149-58 pubmed publisher
    ..While Aer seems to be important during the initiation phase of colonization, FlhD/FlhC appears to be of disadvantage during maintenance phase...
  31. Reiss D, Baliga N, Bonneau R. Integrated biclustering of heterogeneous genome-wide datasets for the inference of global regulatory networks. BMC Bioinformatics. 2006;7:280 pubmed
    ..We have performed a thorough comparison of cMonkey results against other clustering methods, and find that cMonkey biclusters are more parsimonious with all available evidence for co-regulation. ..
  32. Ko M, Park C. H-NS-Dependent regulation of flagellar synthesis is mediated by a LysR family protein. J Bacteriol. 2000;182:4670-2 pubmed
    ..Furthermore, the expression of the hdfR gene was shown to be negatively regulated by H-NS. ..
  33. Wang S, Matsumura P, Westbrook E. Crystallization and preliminary X-ray crystallographic analysis of FlhD/FlhC complex from Escherichia coli. Acta Crystallogr D Biol Crystallogr. 2001;57:734-6 pubmed
    The heterotetrameric (C(2)D(2)) FlhD/FlhC complex was first discovered as a transcriptional activator of the flagellar genes in Escherichia coli...
  34. Kalir S, Mangan S, Alon U. A coherent feed-forward loop with a SUM input function prolongs flagella expression in Escherichia coli. Mol Syst Biol. 2005;1:2005.0006 pubmed
    ..The SUM-FFL in this system works as theoretically predicted despite being embedded in at least two additional feedback loops. The present function might be carried out by the SUM-FFL in systems found across organisms. ..
  35. Campos A, Matsumura P, Volz K. Crystallization and preliminary X-ray analysis of FlhD from Escherichia coli. J Struct Biol. 1998;123:269-71 pubmed
    The flhD gene from Escherichia coli codes for one of the transcriptional activators of flagellar genes and is a putative global regulator in the cell...
  36. Pratt L, Kolter R. Genetic analysis of Escherichia coli biofilm formation: roles of flagella, motility, chemotaxis and type I pili. Mol Microbiol. 1998;30:285-93 pubmed
    ..In light of the observations presented here, a working model is discussed that describes the roles of both motility and type I pili in biofilm development. ..
  37. Mitra A, Fay P, Vendura K, Alla Z, Carroll R, Shaw L, et al. ?(N) -dependent control of acid resistance and the locus of enterocyte effacement in enterohemorrhagic Escherichia coli is activated by acetyl phosphate in a manner requiring flagellar regulator FlhDC and the ?(S) antagonist FliZ. Microbiologyopen. 2014;3:497-512 pubmed publisher
    ..Altering the availability of NtrC phosphodonor acetyl phosphate by growth without glucose, with acetate addition, or by deletion of acetate kinase ackA, abrogated NtrC-?(N)-dependent control of flhDC, fliZ, GDAR, and the LEE. ..
  38. Smith T, Hoover T. Deciphering bacterial flagellar gene regulatory networks in the genomic era. Adv Appl Microbiol. 2009;67:257-95 pubmed publisher
    ..Finally, we review the prominent systems that utilize sigma(28) and its antagonist, the anti-sigma(28) factor FlgM, along with some systems that utilize alternative mechanisms for regulating flagellar gene expression. ..
  39. Li B, Li N, Wang F, Guo L, Huang Y, Liu X, et al. Structural insight of a concentration-dependent mechanism by which YdiV inhibits Escherichia coli flagellum biogenesis and motility. Nucleic Acids Res. 2012;40:11073-85 pubmed publisher
    YdiV is a negative regulator of cell motility. It interacts with FlhD(4)C(2) complex, a product of flagellar master operon, which works as the transcription activator of all other flagellar operons...
  40. Bertin P, Terao E, Lee E, Lejeune P, Colson C, Danchin A, et al. The H-NS protein is involved in the biogenesis of flagella in Escherichia coli. J Bacteriol. 1994;176:5537-40 pubmed
    ..The loss of motility resulted from a complete lack of flagella. A decrease in the level of transcription of the flhD and fliA genes, which are both required for the synthesis of flagella, was observed in the presence of an hns ..
  41. Horne S, Sayler J, Scarberry N, Schroeder M, Lynnes T, Prüß B. Spontaneous mutations in the flhD operon generate motility heterogeneity in Escherichia coli biofilm. BMC Microbiol. 2016;16:262 pubmed
    ..We hypothesized that i) spontaneous mutations in the flhD operon can either increase or decrease motility and that ii) the resulting motility heterogeneity in the biofilm ..