1887

Microbiology Society logo

Volume 161, Issue 8

Dual inducer signal recognition by an Mlc homologue Free

Abstract

The Mlc transcription factor in controls the expression of the phosphotransferase system genes implicated in the transport of glucose into the cell. Transport of glucose derepresses Mlc-repressed genes by provoking the sequestration of Mlc to the membrane, via an interaction with the dephosphorylated EIIB domain of the glucose transporter, PtsG. NagC, a paralogue of Mlc in , regulates the use of the amino sugar -acetylglucosamine (GlcNAc). Both Mlc and NagC are members of the ROK (Repressors, ORFs and Kinases) family. expresses a close orthologue of Mlc, VC2007, which represses the Mlc target, in . However, VC2007 is not sensitive to growth on glucose but responds to growth on -acetylglucosamine (GlcNAc). We show that growth on GlcNAc generates two different signals, which relieve VC2007 repression of in . The majority of the loss of repression is due to VC2007 interacting with dephosphorylated NagE, the GlcNAc-specific transporter. However, a minor part is due to VC2007 binding GlcNAc6P. These two inducing signals are independent and can be separated by mutations in VC2007 eliminating sensitivity to one or other signal. In addition we show that, although most induction of Mlc-repressed genes is dependent upon the interaction of Mlc with PtsG in , Mlc can also bind to NagE, but it is not sensitive to GlcNAc6P. These observations shed light on how ROK family homologues have evolved in their ability to sense glucose and GlcNAc and of the shift between recognition of different categories of inducer.

  • Received:
  • Accepted:
  • Published Online:
© Microbiology Society
Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.000126
2015-08-01
2024-04-18
Loading full text...

Full text loading...

/deliver/fulltext/micro/161/8/1694.html?itemId=/content/journal/micro/10.1099/mic.0.000126&mimeType=html&fmt=ahah

References

  1. Baba T., Ara T., Hasegawa M., Takai Y., Okumura Y., Baba M., Datsenko K.A., Tomita M., Wanner B.L., Mori H. 2006; Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection. Mol Syst Biol 2:0008 [View Article][PubMed]
     [Google Scholar]
  2. Berg T., Schild S., Reidl J. 2007; Regulation of the chitobiose-phosphotransferase system in Vibrio cholerae . Arch Microbiol 187:433–439 [View Article][PubMed]
     [Google Scholar]
  3. Bertram R., Rigali S., Wood N., Lulko A.T., Kuipers O.P., Titgemeyer F. 2011; Regulon of the N-acetylglucosamine utilization regulator NagR in Bacillus subtilis . J Bacteriol 193:3525–3536 [View Article][PubMed]
     [Google Scholar]
  4. Bréchemier-Baey D., Domínguez-Ramírez L., Plumbridge J. 2012; The linker sequence, joining the DNA-binding domain of the homologous transcription factors, Mlc and NagC, to the rest of the protein, determines the specificity of their DNA target recognition in Escherichia coli . Mol Microbiol 85:1007–1019 [View Article][PubMed]
     [Google Scholar]
  5. Bréchemier-Baey D., Domínguez-Ramírez L., Oberto J., Plumbridge J. 2015; Operator recognition by the ROK transcription factor family members, NagC and Mlc. Nucleic Acids Res 43:361–372 [View Article][PubMed]
     [Google Scholar]
  6. Buhr A., Flükiger K., Erni B. 1994; The glucose transporter of Escherichia coli. Overexpression, purification, and characterization of functional domains. J Biol Chem 269:23437–23443[PubMed]
     [Google Scholar]
  7. Conejo M.S., Thompson S.M., Miller B.G. 2010; Evolutionary bases of carbohydrate recognition and substrate discrimination in the ROK protein family. J Mol Evol 70:545–556 [View Article][PubMed]
     [Google Scholar]
  8. Curtis S.J., Epstein W. 1975; Phosphorylation of D-glucose in Escherichia coli mutants defective in glucosephosphotransferase, mannosephosphotransferase, and glucokinase. J Bacteriol 122:1189–1199[PubMed]
     [Google Scholar]
  9. Dahl M.K., Schmiedel D., Hillen W. 1995; Glucose and glucose-6-phosphate interaction with Xyl repressor proteins from Bacillus spp. may contribute to regulation of xylose utilization. J Bacteriol 177:5467–5472[PubMed]
     [Google Scholar]
  10. Datsenko K.A., Wanner B.L. 2000; One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc Natl Acad Sci U S A 97:6640–6645 [View Article][PubMed]
     [Google Scholar]
  11. de Vos M.G., Poelwijk F.J., Battich N., Ndika J.D., Tans S.J. 2013; Environmental dependence of genetic constraint. PLoS Genet 9:e1003580 [View Article][PubMed]
     [Google Scholar]
  12. Decker K., Plumbridge J., Boos W. 1998; Negative transcriptional regulation of a positive regulator: the expression of malT, encoding the transcriptional activator of the maltose regulon of Escherichia coli, is negatively controlled by Mlc. Mol Microbiol 27:381–390 [View Article][PubMed]
     [Google Scholar]
  13. Deutscher J., Francke C., Postma P.W. 2006; How phosphotransferase system-related protein phosphorylation regulates carbohydrate metabolism in bacteria. Microbiol Mol Biol Rev 70:939–1031 [View Article][PubMed]
     [Google Scholar]
  14. Fillenberg S.B., Grau F.C., Seidel G., Muller Y.A. 2015; Structural insight into operator dre-sites recognition and effector binding in the GntR/HutC transcription regulator NagR. Nucleic Acids Res 43:1283–1296 [View Article][PubMed]
     [Google Scholar]
  15. Fillinger S., Boschi-Muller S., Azza S., Dervyn E., Branlant G., Aymerich S. 2000; Two glyceraldehyde-3-phosphate dehydrogenases with opposite physiological roles in a nonphotosynthetic bacterium. J Biol Chem 275:14031–14037 [View Article][PubMed]
     [Google Scholar]
  16. Gärtner D., Degenkolb J., Ripperger J.A., Allmansberger R., Hillen W. 1992; Regulation of the Bacillus subtilis W23 xylose utilization operon: interaction of the Xyl repressor with the xyl operator and the inducer xylose. Mol Gen Genet 232:415–422 [View Article][PubMed]
     [Google Scholar]
  17. Gaugué I., Oberto J., Plumbridge J. 2014; Regulation of amino sugar utilization in Bacillus subtilis by the GntR family regulators, NagR and GamR. Mol Microbiol 92:100–115 [View Article][PubMed]
     [Google Scholar]
  18. Ghosh S., Rao K.H., Sengupta M., Bhattacharya S.K., Datta A. 2011; Two gene clusters co-ordinate for a functional N-acetyl glucosamine catabolic pathway in Vibrio cholerae . Mol Microbiol 80:1549–1560 [View Article][PubMed]
     [Google Scholar]
  19. Hosono K., Kakuda H., Ichihara S. 1995; Decreasing accumulation of acetate in a rich medium by Escherichia coli on introduction of genes on a multicopy plasmid. Biosci Biotechnol Biochem 59:256–261 [View Article][PubMed]
     [Google Scholar]
  20. Houot L., Chang S., Pickering B.S., Absalon C., Watnick P.I. 2010; The phosphoenolpyruvate phosphotransferase system regu lates Vibrio cholerae biofilm formation through multiple independent pathways. J Bacteriol 192:3055–3067 [View Article][PubMed]
     [Google Scholar]
  21. Huergo L.F., Chandra G., Merrick M. 2013; P(II) signal transduction proteins: nitrogen regulation and beyond. FEMS Microbiol Rev 37:251–283[PubMed] [CrossRef]
     [Google Scholar]
  22. Joyet P., Bouraoui H., Aké F.M., Derkaoui M., Zébré A.C., Cao T.N., Ventroux M., Nessler S., Noirot-Gros M.F., other authors. 2013; Transcription regulators controlled by interaction with enzyme IIB components of the phosphoenolpyruvate: sugar phosphotransferase system. Biochim Biophys Acta 1834:1415–1424 [View Article][PubMed]
     [Google Scholar]
  23. Joyet J., Derkaoui M., Bouraoui H., Deutscher J. 2015; PTS-mediated regulation of the transcription activator MtlR from different species: surprising differences despite strong sequence conservation. In J Mol Microbiol Biotechnol 2594–105 [CrossRef]
     [Google Scholar]
  24. Kim S.-Y., Nam T.-W., Shin D., Koo B.-M., Seok Y.-J., Ryu S. 1999; Purification of Mlc and analysis of its effects on the pts expression in Escherichia coli . J Biol Chem 274:25398–25402 [View Article][PubMed]
     [Google Scholar]
  25. Kimata K., Inada T., Tagami H., Aiba H. 1998; A global repressor (Mlc) is involved in glucose induction of the ptsG gene encoding major glucose transporter in Escherichia coli . Mol Microbiol 29:1509–1519 [View Article][PubMed]
     [Google Scholar]
  26. Lee S.-J., Boos W., Bouché J.-P., Plumbridge J. 2000; Signal transduction between a membrane-bound transporter, PtsG, and a soluble transcription factor, Mlc, of Escherichia coli . EMBO J 19:5353–5361 [View Article][PubMed]
     [Google Scholar]
  27. Lengeler J.W., Jahreis K., Wehmeier U.F. 1994; Enzymes II of the phospho enol pyruvate-dependent phosphotransferase systems: their structure and function in carbohydrate transport. Biochim Biophys Acta 1188:1–28 [View Article][PubMed]
     [Google Scholar]
  28. Lévy S., Zeng G.-Q., Danchin A. 1990; Cyclic AMP synthesis in Escherichia coli strains bearing known deletions in the pts phospho transferase operon. Gene 86:27–33 [View Article][PubMed]
     [Google Scholar]
  29. Madan Babu M., Teichmann S.A. 2003; Evolution of transcription factors and the gene regulatory network in Escherichia coli . Nucleic Acids Res 31:1234–1244 doi:10.1093/nar/gkg210 [PubMed] [CrossRef]
     [Google Scholar]
  30. Meibom K.L., Li X.B., Nielsen A.T., Wu C.Y., Roseman S., Schoolnik G.K. 2004; The Vibrio cholerae chitin utilization program. Proc Natl Acad Sci U S A 101:2524–2529 [View Article][PubMed]
     [Google Scholar]
  31. Miller J.H. 1972 Experiments in Molecular Genetics New York: Cold Spring Harbor, Cold Spring Harbor laboratory;
     [Google Scholar]
  32. Miyazono K., Tabei N., Morita S., Ohnishi Y., Horinouchi S., Tanokura M. 2012; Substrate recognition mechanism and substrate-dependent conformational changes of an ROK family glucokinase from Streptomyces griseus . J Bacteriol 194:607–616 [View Article][PubMed]
     [Google Scholar]
  33. Nam T.-W., Cho S.-H., Shin D., Kim J.-H., Jeong J.-Y., Lee J.-H., Roe J.-H., Peterkofsky A., Kang S.-O., other authors. 2001; The Escherichia coli glucose transporter enzyme IICB(Glc) recruits the global repressor Mlc. EMBO J 20:491–498 [View Article][PubMed]
     [Google Scholar]
  34. Nam T.W., Jung H.I., An Y.J., Park Y.H., Lee S.H., Seok Y.J., Cha S.S. 2008; Analyses of Mlc-IIBGlc interaction and a plausible molecular mechanism of Mlc inactivation by membrane sequestration. Proc Natl Acad Sci U S A 105:3751–3756 [View Article][PubMed]
     [Google Scholar]
  35. Neidhardt F.C., Bloch P.L., Smith D.F. 1974; Culture medium for enterobacteria. J Bacteriol 119:736–747[PubMed]
     [Google Scholar]
  36. Park J.T. 2001; Identification of a dedicated recycling pathway for anhydro-N-acetylmuramic acid and N-acetylglucosamine derived from Escherichia coli cell wall murein. J Bacteriol 183:3842–3847 [View Article][PubMed]
     [Google Scholar]
  37. Pennetier C., Domínguez-Ramírez L., Plumbridge J. 2008; Different regions of Mlc and NagC, homologous transcriptional repressors con trolling expression of the glucose and N-acetylglucosamine phospho transferase systems in Escherichia coli, are required for inducer signal recognition. Mol Microbiol 67:364–377 [View Article][PubMed]
     [Google Scholar]
  38. Pickering B.S., Lopilato J.E., Smith D.R., Watnick P.I. 2014; The transcription factor Mlc promotes Vibrio cholerae biofilm formation through repression of phosphotransferase system components. J Bacteriol 196:2423–2430 [View Article][PubMed]
     [Google Scholar]
  39. Plata G., Fuhrer T., Hsiao T.L., Sauer U., Vitkup D. 2012; Global probabilistic annotation of metabolic networks enables enzyme discovery. Nat Chem Biol 8:848–854 [View Article][PubMed]
     [Google Scholar]
  40. Plumbridge J.A. 1991; Repression and induction of the nag regulon of Escherichia coli K-12: the roles of nagC nagA in maintenance of the uninduced state. Mol Microbiol 5:2053–2062 [View Article][PubMed]
     [Google Scholar]
  41. Plumbridge J. 1998a; Control of the expression of the manXYZ operon in Escherichia coli: Mlc is a negative regulator of the mannose PTS. Mol Microbiol 27:369–380 [View Article][PubMed]
     [Google Scholar]
  42. Plumbridge J. 1998b; Expression of ptsG, the gene for the major glucose PTS transporter in Escherichia coli, is repressed by Mlc and induced by growth on glucose. Mol Microbiol 29:1053–1063 [View Article][PubMed]
     [Google Scholar]
  43. Plumbridge J. 1999; Expression of the phosphotransferase system both mediates and is mediated by Mlc regulation in Escherichia coli . Mol Microbiol 33:260–273 [View Article][PubMed]
     [Google Scholar]
  44. Plumbridge J. 2001a; Regulation of PTS gene expression by the homologous transcriptional regulators, Mlc and NagC, in Escherichia coli (or how two similar repressors can behave differently). J Mol Microbiol Biotechnol 3:371–380[PubMed]
     [Google Scholar]
  45. Plumbridge J. 2001b; DNA binding sites for the Mlc and NagC proteins: regulation of nagE, encoding the N-acetylglucosamine-specific transporter in Escherichia coli . Nucleic Acids Res 29:506–514 [View Article][PubMed]
     [Google Scholar]
  46. Plumbridge J. 2002; Regulation of gene expression in the PTS in Escherichia coli: the role and interactions of Mlc. Curr Opin Microbiol 5:187–193 [View Article][PubMed]
     [Google Scholar]
  47. Plumbridge J. 2009; An alternative route for recycling of N-acetylglucosamine from peptidoglycan involves the N-acetylglucosamine phosphotransferase system in Escherichia coli . J Bacteriol 191:5641–5647 [View Article][PubMed]
     [Google Scholar]
  48. Poelwijk F.J., Kiviet D.J., Tans S.J. 2006; Evolutionary potential of a duplicated repressor-operator pair: simulating pathways using mutation data. PLOS Comput Biol 2:e58 [View Article][PubMed]
     [Google Scholar]
  49. Poelwijk F.J., de Vos M.G., Tans S.J. 2011a; Tradeoffs and optimality in the evolution of gene regulation. Cell 146:462–470 [View Article][PubMed]
     [Google Scholar]
  50. Poelwijk F.J., Heyning P.D., de Vos M.G., Kiviet D.J., Tans S.J. 2011b; Optimality and evolution of transcriptionally regulated gene expression. BMC Syst Biol 5:128 [View Article][PubMed]
     [Google Scholar]
  51. Postma P.W., Lengeler J.W., Jacobson G.R. 1996; Phosphoenolpyruvate:carbohydrate phosphotransferase systems. In Escherichia Coli and Salmonella, Cellular and Molecular Biology pp. 1149–1174 Edited by Neidhardt F. C., Curtiss R., Ingraham J. L., Lin E. C. C., Low K. B., Magasanik B., Reznikoff W. S., Riley M., Schaechter M., Umbargo H. E. Washington, DC: American Society for Microbiology;
     [Google Scholar]
  52. Ringquist S., Shinedling S., Barrick D., Green L., Binkley J., Stormo G.D., Gold L. 1992; Translation initiation in Escherichia coli: sequences within the ribosome-binding site. Mol Microbiol 6:1219–1229 [View Article][PubMed]
     [Google Scholar]
  53. Rodionov D.A., Mironov A.A., Gelfand M.S. 2001; Transcriptional regulation of pentose utilisation systems in the Bacillus/Clostridium group of bacteria. FEMS Microbiol Lett 205:305–314 [View Article][PubMed]
     [Google Scholar]
  54. Scheler A., Hillen W. 1994; Regulation of xylose utilization in Bacillus licheniformis: Xyl repressor-xyl-operator interaction studied by DNA modification protection and interference. Mol Microbiol 13:505–512 [View Article][PubMed]
     [Google Scholar]
  55. Schiefner A., Gerber K., Seitz S., Welte W., Diederichs K., Boos W. 2005; The crystal structure of Mlc, a global regulator of sugar metabolism in Escherichia coli . J Biol Chem 280:29073–29079 [View Article][PubMed]
     [Google Scholar]
  56. Schumacher M.A., Seidel G., Hillen W., Brennan R.G. 2007; Structural mechanism for the fine-tuning of CcpA function by the small molecule effectors glucose 6-phosphate and fructose 1,6-bisphosphate. J Mol Biol 368:1042–1050 [View Article][PubMed]
     [Google Scholar]
  57. Seitz S., Lee S.-J., Pennetier C., Boos W., Plumbridge J. 2003; Analysis of the interaction between the global regulator Mlc and EIIBGlc of the glucose-specific phosphotransferase system in Escherichia coli . J Biol Chem 278:10744–10751 [View Article][PubMed]
     [Google Scholar]
  58. Sizemore C., Buchner E., Rygus T., Witke C., Götz F., Hillen W. 1991; Organization, promoter analysis and transcriptional regulation of the Staphylococcus xylosus xylose utilization operon. Mol Gen Genet 227:377–384 [View Article][PubMed]
     [Google Scholar]
  59. Sizemore C., Wieland B., Götz F., Hillen W. 1992; Regulation of Staphylococcus xylosus xylose utilization genes at the molecular level. J Bacteriol 174:3042–3048[PubMed]
     [Google Scholar]
  60. Sonnhammer E.L., Gabaldón T., Sousa da Silva A.W., Martin M., Robinson-Rechavi M., Boeckmann B., Thomas P.D., Dessimoz C. Quest for Orthologs consortium 2014; Big data and other challenges in the quest for orthologs. Bioinformatics 30:2993–2998 [View Article][PubMed]
     [Google Scholar]
  61. Tanaka Y., Kimata K., Aiba H. 2000; A novel regulatory role of glucose transporter of Escherichia coli: membrane sequestration of a global repressor Mlc. EMBO J 19:5344–5352 [View Article][PubMed]
     [Google Scholar]
  62. Tanaka Y., Itoh F., Kimata K., Aiba H. 2004; Membrane localization itself but not binding to IICB is directly responsible for the inactivation of the global repressor Mlc in Escherichia coli . Mol Microbiol 53:941–951 [View Article][PubMed]
     [Google Scholar]
  63. Titgemeyer F., Reizer J., Reizer A., Saier M.H. Jr 1994; Evolutionary relationships between sugar kinases and transcriptional repressors in bacteria. Microbiology 140:2349–2354 [View Article][PubMed]
     [Google Scholar]
  64. White R.J. 1968; Control of amino sugar metabolism in Escherichia coli and isolation of mutants unable to degrade amino sugars. Biochem J 106:847–858[PubMed] [CrossRef]
     [Google Scholar]
  65. Yang C., Rodionov D.A., Li X., Laikova O.N., Gelfand M.S., Zagnitko O.P., Romine M.F., Obraztsova A.Y., Nealson K.H., Osterman A.L. 2006; Comparative genomics and experimental characterization of N-acetylglucosamine utilization pathway of Shewanella oneidensis. J Biol Chem. 281:29872–29885 [View Article][PubMed]
     [Google Scholar]
  66. Zhao G., Pease A.J., Bharani N., Winkler M.E. 1995; Biochemical characterization of gapB-encoded erythrose 4-phosphate dehydrogenase of Escherichia coli K-12 and its possible role in pyridoxal 5′-phosphate biosynthesis. J Bacteriol 177:2804–2812[PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.000126
Loading
Dual inducer signal recognition by an Mlc homologue
Microbiology 161, 1694 (2015); https://doi.org/10.1099/mic.0.000126
/content/journal/micro/10.1099/mic.0.000126
/content/journal/micro/10.1099/mic.0.000126
Loading

Data & Media loading...

Supplements

Supplementary Data

PDF

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error