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Export of metabolites by the proteins of the DMT and RhtB families and its possible role in intercellular communication

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Abstract

The earlier published and new experimental data are summarized on the properties of the genes encoding the membrane proteins of the DMT family (RhtA (YbiF), EamA (YdeD), YijE, YddG, YedA, PecM, eukaryotic nucleotide sugar, triose phosphate/phosphate, and hexose phosphate transporters), the RhtB/LysE family (RhtB, RhtC, LeuE, YahN, EamB (YfiK), ArgO (YggA), CmaU), as well as some other families (YicM, YdhC, YdeAB, YdhE (NorE)). These proteins are involved in the export of amino acids, purines, and other metabolites from the cell. The expression of most of the genes encoding these proteins is not induced by the substrates they transport but is controlled by the global regulation systems, such as the Lrp protein, and activated by the signal compounds involved in the intracellular communication. The level of expression, assessed in experiments on translational fusion of the corresponding bacterial genes with the β-galactosidase gene, depends on the growth phase of the bacterial culture, composition of the medium, and some stress factors, such as pH, osmolarity or decreased aeration. The efflux of normal cell metabolites is assumed to be the natural function of these proteins. This function may play a role in density-dependent behavior of cell populations (quorum sensing). It may have been enhanced in the course of evolution via specialization of these proteins in the efflux of compounds derived from metabolic intermediates and adjusted to the role of transmitters.

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References

  1. Jack, D.L., Yang, N.M., and Saier, M.H., The Drug/Metabolite Transporter Superfamily, Eur. J. Biochem., 2001, vol. 268, no. 13, pp. 3620–3639.

    Article  PubMed  CAS  Google Scholar 

  2. Aleshin, V.V., Zakataeva, N.P., and Livshits, V.A., A New Family of Amino Acid Efflux Proteins, Trends Biochem. Sci., 1999, vol. 24, pp. 133–135.

    Article  PubMed  CAS  Google Scholar 

  3. Vrljić, M., Garg, J., Bellmann, A., Wachi, S., Freudl, R., Malecki, M.J., Sahm, H., Kozina, V.J., Eggeling, L., and Saier, M.H., The LysE Superfamily: Topology of the Lysine Exporter LysE of Corynebacterium glutamicum, a Paradigm for a Novel Superfamily of Transmembrane Solute Translocators, J. Mol. Microbiol. Biotechnol, 1999, vol. 1, no. 2, pp. 327–336.

    PubMed  Google Scholar 

  4. Vrljić, M., Sahm, H.., and Eggeling, L., A New Type of Transporter with a New Type of Cellular Function: L-Lysine export from Corynebacterium glutamicum, Mol. Microbiol., 1996, vol. 22, pp. 815–826.

    Article  PubMed  Google Scholar 

  5. Zakataeva, N.P., Aleshin, V.V., Tokmakova, I.L., Troshin, P.V., and Livshits, V.A., The Novel Transmembrane Escherichia coli Proteins Involved in the Amino Acid Efflux, FEBS Lett., 1999, vol. 452, no. 3, pp. 228–232.

    Article  PubMed  CAS  Google Scholar 

  6. Daßler, T., Maier, T., Winterhalter, C., and Böck, A., Identification of a Major Facilitator Protein from Escherichia coli Involved in Efflux of Metabolites of the Cysteine Pathway, Mol. Microbiol., 2000, vol. 36, pp. 1101–1112.

    Article  PubMed  Google Scholar 

  7. Livshits, V.A., Zakataeva, N.P., Nakanishi, K., Aleshin, V.V., Troshin, P.V., and Tokmakova, I.L., An Escherichia coli DNA Fragment Determining Increased Production of L-Amino Acids (Variants); a Method for Obtaining L-Amino Acids, RF Patent no. 2175351, October 2001.

  8. Livshits, V.A., Zakataeva, N.P., Aleshin, V.V., and Vitushkina, M.V., Identification and Characterization of the New Gene rhtA Involved in Threonine and Homoserine Efflux in Escherichia coli, Res. Microbiol., 2003, vol. 154, pp. 123–135.

    Article  PubMed  CAS  Google Scholar 

  9. Livshits, V.A., Vitushkina, M.V., Mashko, S.V., Doroshenko, V.G., Biryukova, I.V., Katashkina, Zh.I., Skorokhodova, A.Yu., and Belareva, A.V., A Method for Obtaining L-Amino Acids; an Escherichia coli Strain Producing L-Amino Acids (Variants), RF Patent no. 2222596, January 2004.

  10. Livshits, V.A., Vitushkina, M.V., Gusyatiner, M.M., Ziyatdinov, M.Kh., Akhverdyan, V.Z., Savrasova, E.A., Doroshenko, V.G., and Mashko, S.V., A Method for Obtaining L-Amino Acids; an Escherichia coli Strain Producing L-Amino Acids (Variants), RF Patent no. 2229513, May 2004.

  11. Kutukova, E.A., Livshits, V.A., Altman, I.P., Ptitsyn, L.R., Zyiatdinov, M.H., Tokmakova, I.L., and Zakataeva, N.P., The yeaS (leuE) Gene of Escherichia coli Encodes an Exporter of Leucine, and the Lrp Protein Regulates Its Expression, FEBS Lett., 2005, vol. 579, pp. 4629–4634.

    Article  PubMed  CAS  Google Scholar 

  12. Livshits, V.A., Zakataeva, N.P., Gronskiy, S.V., Vitushkina, M.V., and Novikova, A.E., A Method for Obtaining Purine Nucleosides and Nucleotides; a Strain Producing Purine Nucleosides (Variants), RF Patent no. 2239656, November 2004.

  13. Zakataeva, N.P., Livshits, V.A., and Gronskiy, S.V., A Method for Obtaining Purine Inosine and 5′-Inosinic Acid; an Escherichia coli Strain Producing Inosine, RF Patent no. 2244003, January 2005.

  14. Gronskiy, S.V., Zakataeva, N.P., and Livshits, V.A., A Method for Obtaining Purine Inosine and 5′-Inosinic Acid; an Escherichia coli Strain Producing Inosine, RF Patent no. 2244004, January 2005.

  15. Praillet, T., Reverchon, S., Robert-Baudouy, J., and Nasser, W., The PecM Protein Is Necessary for the DNA-Binding Capacity of the PecS Repressor, One of the Regulators of Virulence-Factor Synthesis in Erwinia chrysanthemi, FEMS Microbiol. Lett., 1997, vol. 154, no. 2, pp. 265–270.

    Article  PubMed  CAS  Google Scholar 

  16. Reverchon, S., Rouanet, C., Expert, D., and Nasser, W., Characterization of Indigoidine Biosynthetic Genes in Erwinia chrysanthemi and Role of This Blue Pigment in Pathogenicity, J. Bacteriol., 2002, vol. 184, no. 3, pp. 654–665.

    Article  PubMed  CAS  Google Scholar 

  17. Zavilgel’sky, G.B. and Manukhov, I.V., Quorum Sensing, or How Bacteria “Talk” to Each Other, Mol. Biol. 2001, vol. 35, no. 2, pp. 268–277 [Mol. Biol. (Engl. Transl.), vol. 35, no. 2, pp. 224–232].

    Google Scholar 

  18. Visick, K.L. and Fugua, C., Decoding Microbial Chatter: Cell-Cell Communication in Bacteria, J. Bacteriol., 2005, vol. 187, no. 16, pp. 5507–5519.

    Article  PubMed  CAS  Google Scholar 

  19. Kaper, J.B. and Sperandio, V., Bacterial Cell-to-Cell Signaling in the Gastrointestinal Tract, Infect. Immun., 2005, vol. 73, no. 6, pp. 3197–3209.

    Article  PubMed  CAS  Google Scholar 

  20. Kaplan, H.B. and Plamann, L., A Myxococcus xanthus Cell Density-Sensing System Required for Multicellular Development, FEMS Microbiol. Lett., 1996, vol. 139, nos. 2–3, pp. 89–95.

    PubMed  CAS  Google Scholar 

  21. Hengge-Aronis, R., Signal Transduction and Regulatory Mechanisms Involved in Control of the σS (RpoS) Subunit of RNA Polymerase, Microbiol. Mol. Biol. Rev., 2002, vol. 66, no. 3, pp. 373–395.

    Article  PubMed  CAS  Google Scholar 

  22. Venturi, V., Control of rpoS Transcription in Escherichia coli and Pseudomonas: Why So Different?, Mol. Microbiol., 2003, vol. 49, no. 1, pp. 1–9.

    Article  PubMed  CAS  Google Scholar 

  23. Khmel, I.A., Regulation of Expression of Bacterial Genes in the Absence of Active Cell Growth, Genetika, 2005, vol. 41, no. 9, pp. 1183–1202 [Russ. J. Genet. (Engl. Transl.), vol. 41, no. 9, pp. 968–984].

    PubMed  CAS  Google Scholar 

  24. Magnusson, L.U., Farewell, A., and Nystrom, T., ppGpp: A Global Regulator in Escherichia coli, Trends Microbiol., 2005, vol. 13, no. 5, pp. 236–242.

    Article  PubMed  CAS  Google Scholar 

  25. Braeken, K., Moris, M., Daniels, R., Vanderleyden, J., and Michiels, J., New Horizons for (p)ppGpp in Bacterial and Plant Physiology, Trends Microbiol., 2006, vol. 14, no. 1, pp. 45–54.

    Article  PubMed  CAS  Google Scholar 

  26. van Delden, C., Comte, R., and Bally, A.M., Stringent Response Activates Quorum Sensing and Modulates Cell Density-Dependent Gene Expression in Pseudomonas aeruginosa, J. Bacteriol., 2001, vol. 183, no. 18, pp. 5376–5384.

    Article  PubMed  Google Scholar 

  27. Calvo, J.M. and Matthews, R.G., The Leucine-Responsive Regulatory Protein, a Global Regulator of Metabolism in Escherichia coli, Microbiol. Rev., 1994, vol. 58, no. 3, pp. 466–490.

    PubMed  CAS  Google Scholar 

  28. Evans, K., Passador, L., Srikumar, R., Tsang, E., Nezelzon, J., and Poole, K., Influence of the MexAB-OprM Multidrug Efflux System on Quorum Sensing in Pseudomonas aeruginosa, J. Bacteriol., 1998, vol. 180, pp. 5443–5447.

    PubMed  CAS  Google Scholar 

  29. Pearson, J.P., van Delden, C., and Iglewski, B.H., Active Efflux and Diffusion Are Involved in Transport of Pseudomonas aeruginosa Cell-to-Cell Signals, J. Bacteriol., 1999, vol. 181, no. 4, pp. 1203–1210.

    PubMed  CAS  Google Scholar 

  30. Maseda, H., Sawada, I., Saito, K., Uchiyama, H., Nakae, T., and Nomura, N., Enhancement of the MexAB-OprM Efflux Pump Expression by a Quorum-Sensing Autoinducer and Its Cancellation by a Regulator, MexT, of the mexEF-oprN Efflux Pump Operon in Pseudomonas aeruginosa, Antimicrob. Agents Chemother., 2004, vol. 48, no. 4, pp. 1320–1328.

    Article  PubMed  CAS  Google Scholar 

  31. Sawada, I., Maseda, H., Nakae, T., Uchiyama, H., Nomura, N., A Quorum-Sensing Autoinducer Enhances the mexAB-oprM Efflux-Pump Expression without the MexR-Mediated Regulation in Pseudomonas aeruginosa, Microbiol. Immunol., 2004, vol. 48, no. 5, pp. 435–439.

    PubMed  CAS  Google Scholar 

  32. Rahmati, S., Yang, S., Davidson, A.L., and Zechiedrich, E.L., Control of the AcrAB Multidrug Efflux Pump by Quorum-Sensing Regulator SdiA, Mol. Microbiol., 2002, vol. 43, no. 3, pp. 677–685.

    Article  PubMed  CAS  Google Scholar 

  33. Franke, I., Resch, A., Daler, T., Maier, T., and Bock, A., YfiK from Escherichia coli Promotes Export of O-Acetylserine and Cysteine, J. Bacteriol., 2003, vol. 185, no. 4, pp. 1161–1166.

    Article  PubMed  CAS  Google Scholar 

  34. Bellmann, A., Vrljic, M., Patek, M., Sahm, H., Kramer, R., and Eggeling, L., Expression Control and Specificity of the Basic Amino Acid Exporter LysE of Corynebacterium glutamicum, Arch. Microbiol., 2001, vol. 147, no. 7, pp. 1765–1774.

    CAS  Google Scholar 

  35. Nandieni, R. and Gowrishankar, J., Evidence for an Arginine Exporter Encoded by yggA (argO) That Is Regulated by the LysR-Type Transcriptional Regulator ArgP in Escherichia coli, J. Bacteriol., 2004, vol. 186, no. 11, pp. 3539–3546.

    Article  CAS  Google Scholar 

  36. Eggeling, L. and Sahm, H., New Ubiquitous Translocators: Amino Acid Export by Corynebacterium glutamicum and Escherichia coli, Arch. Microbiol., 2003, vol. 180, no. 3, pp. 155–160.

    Article  PubMed  CAS  Google Scholar 

  37. Surette, M.G., Miller, M.B., and Bassler, B.L., Quorum Sensing in Escherichia coli, Salmonella typhimurium, and Vibrio harveyi: A New Family of Genes Responsible for Autoinducer Production, Proc. Natl. Acad. Sci. USA, 1999, vol. 96, no. 4, pp. 1639–1644.

    Article  PubMed  CAS  Google Scholar 

  38. Ahmer, B.M.M., Cell-to-Cell Signaling in Escherichia coli and Salmonella enterica, Mol. Microbiol., 2004, vol. 52, no. 4, pp. 933–945.

    Article  PubMed  CAS  Google Scholar 

  39. DeLisa, M.P., Wu, C.-F., Wang, L., Valdes, J.J., and Bentley, W.E., DNA Microarray-Based Identification of Genes Controlled by Autoinducer 2-Stimulated Quorum Sensing in Escherichia coli, J. Bacteriol., 2001, vol. 183, no. 18, pp. 5239–5247.

    Article  PubMed  CAS  Google Scholar 

  40. van Houdt, R., Aertsen, A., Moons, P., Vanoirbeek, K., and Michiels, C.W., N-Acyl-L-Homoserine Lactone Signal Interception by Escherichia coli, FEMS Microbiol. Lett., 2006, vol. 256.

  41. Ullrich, M. and Bender, C.L., The Biosynthetic Gene Cluster for Coronamic Acid, an Ethylcyclopropyl Amino Acid, Contains Genes Homologous to Amino Acid-Activating Enzymes and Thioesterases, J. Bacteriol., 1994, vol. 176, no. 24, pp. 7574–7586.

    PubMed  CAS  Google Scholar 

  42. Schuster, M., Lostroh, C.P., Ogi, T., and Greenberg, E.P., Identification, Timing, and Signal Specificity of Pseudomonas aeruginosa Quorum-Controlled Genes: A Transcriptome Analysis, J. Bacteriol., 2003, vol. 185, no. 7, pp. 2066–2079.

    Article  PubMed  CAS  Google Scholar 

  43. Wagner, V.E., Bushnell, D., Passador, L., Brooks, A.I., and Iglewski, B.H., Microarray Analysis of Pseudomonas aeruginosa Quorum-Sensing Regulons: Effects of Growth Phase and Environment, J. Bacteriol., 2003, vol. 185, no. 7, pp. 2080–2095.

    Article  PubMed  CAS  Google Scholar 

  44. Tani, T.H., Khodursky, A., Blumenthal, R.M., Brown, P.O., and Matthews, R.G., Adaptation to Famine: A Family of Stationary-Phase Genes Revealed by Microarray Analysis, Proc. Natl. Acad. Sci. USA, 2002, vol. 99, no. 21, pp. 13471–13476.

    Article  PubMed  CAS  Google Scholar 

  45. Buznikov, G.A. and Turpaev, T.M., Intracellular Functions of Neurotransmitters: Phylogenetic and Ontogenetic Aspects, Zh. Evol. Biokhim. Fiziol., 1987, vol. 23, no. 4, pp. 423–432.

    PubMed  CAS  Google Scholar 

  46. Buznikov, G.A., Shmukler, Y.B., and Lauder, J.M., Changes in the Physiological Roles of Neurotransmitters during Individual Development, Neurosci. Behav. Physiol., 1999, vol. 29, no. 1, pp. 11–21.

    PubMed  CAS  Google Scholar 

  47. Oleskin, A.V. and Kirovskaya, T.A., Research on Population Organization and Communication in Microorganisms, Mikrobiologiya, 2006, vol. 75, no. 4 [Microbiology (Engl. Transl.), vol. 75, no. 4].

  48. Berninsone, P.M. and Hirschberg, C.B., Nucleotide Sugar Transporters of the Golgi Apparatus, Curr. Opin. Struct. Biol., 2000, vol. 10, no. 5, pp. 542–547.

    Article  PubMed  CAS  Google Scholar 

  49. Knappe, S., Flugge, U.-I., and Fischer, K., Analysis of the Plastidic Phosphate Translocator Gene Family in Arabidopsis and Identification of New Phosphate Translocator-Homologous Transporters, Classified by Their Putative Substrate-Binding Site, Plant Physiol., 2003, vol. 131, no. 3, pp. 1178–1190.

    Article  PubMed  CAS  Google Scholar 

  50. Hirschberg, C.B., Golgi Nucleotide Sugar Transport and Leukocyte Adhesion Deficiency II, J. Clin. Invest., 2001, vol. 108, no. 1, pp. 3–6.

    Article  PubMed  CAS  Google Scholar 

  51. Hwang, H.Y. and Horvitz, H.R., The SQV-1 UDP-Glucuronic Acid Decarboxylase and the SQV-7 Nucleotide-Sugar Transporter May Act in the Golgi Apparatus To Affect Caenorhabditis elegans Vulval Morphogenesis and Embryonic Development, Proc. Natl. Acad. Sci. USA, 2002, vol. 99, no. 22, pp. 14218–14223.

    Article  PubMed  CAS  Google Scholar 

  52. Ishikawa, H.O., Higashi, S., Ayukawa, T., Sasamura, T., Kitagawa, M., Harigaya, K., Aoki, K., Ishida, N., Sanai, Y., and Matsuno, K., Notch Deficiency Implicated in the Pathogenesis of Congenital Disorder of Glycosylation IIc, Proc. Natl. Acad. Sci. USA, 2005, vol. 102, no. 51, pp. 18532–18537.

    Article  PubMed  CAS  Google Scholar 

  53. Sacks, D.L., Modi, G., Rowton, E., Späth, G., Epstein, L., Turco, S.J., and Beverley, S.M., The Role of Phosphoglycans in Leishmania-Sand Fly Interactions, Proc. Natl. Acad. Sci. USA, 2000, vol. 97, no. 1, pp. 406–411.

    Article  PubMed  CAS  Google Scholar 

  54. Niewiadomski, P., Knappe, S., Geimer, S., Fischer, K., Schulz, B., Unte, U.S., Rosso, M.G., Ache, P., Flugge, U.-I., and Schneider, A., The Arabidopsis Plastidic Glucose-6-Phosphate/Phosphate Translocator GPT1 Is Essential for Pollen Maturation and Embryo Sac Development, Plant Cell, 2005, vol. 17, no. 3, pp. 760–775.

    Article  PubMed  CAS  Google Scholar 

  55. Gronskiy, S.V., Zakataeva, N.P., Vitushkina, M.V., Ptitsyn, L.R., Altman, I.B., Novikova, A.E., and Livshits, V.A., The yicM (nepI) Gene of Escherichia coli Encodes a Major Facilitator Superfamily Protein Involved in Efflux of Purine Ribonucleosides, FEMS Microbiol. Lett., 2005, vol. 250, no. 1, pp. 39–47.

    Article  PubMed  CAS  Google Scholar 

  56. Yang, S., Clayton, S.R., and Zechiedrich, E.L., Relative Contributions of the AcrAB, MdfA and NorE Efflux Pumps to Quinolone Resistance in Escherichia coli, J. Antimicrob. Chemother., 2003, vol. 51, no. 3, pp. 545–556.

    Article  PubMed  CAS  Google Scholar 

  57. Yang, S., Lopez, C.R., and Zechiedrich, E.L., Quorum Sensing and Multidrug Transporters in Escherichia coli, Proc. Natl. Acad Sci. USA, 2006, vol. 103, no. 7, pp. 2386–2391.

    Article  PubMed  CAS  Google Scholar 

  58. Ullmann, A. and Danchin, A., Role of Cyclic AMP in Bacteria, Adv. Cyclic Nucleotide Res., 1983, vol. 30, pp. 1–53.

    Google Scholar 

  59. Mann, S.K. and Firtel, R.A., cAMP-Dependent Protein Kinase Differentially Regulates Prestalk and Prespore Differentiation during Dictyostelium Development, Development, 1993, vol. 119, no. 1, pp. 135–146.

    PubMed  CAS  Google Scholar 

  60. Williams, M. and Jarvis, M.F., Purinergic and Pyrimidinergic Receptors as Potential Drug Targets, Biochem. Pharmacol., 2000, vol. 59, no. 10, pp. 1173–1185.

    Article  PubMed  CAS  Google Scholar 

  61. Jenal, U., Cyclic Di-Guanosine-Monophosphate Comes of Age: A Novel Secondary Messenger Involved in Modulating Cell Surface Structures in Bacteria?, Curr. Opin. Microbiol., 2004, vol. 7, no. 2, pp. 185–191.

    Article  PubMed  CAS  Google Scholar 

  62. Römling, U., Gomelsky, M., and Galperin, M.Y., c-di-GMP: The Dawning of a Novel Bacterial Signaling System, Mol. Microbiol., 2005, vol. 57, no. 3, pp. 629–639.

    Article  PubMed  CAS  Google Scholar 

  63. Arnold, C.N., McElhanon, J., Lee, A., Leonhart, R., and Siegele, D.A., Global Analysis of Escherichia coli Gene Expression during the Acetate-Induced Acid Tolerance Response, J. Bacteriol., 2001, vol. 183, no. 7, pp. 2178–2186.

    Article  PubMed  CAS  Google Scholar 

  64. Rinas, U., Hellmuth, K., Kang, R., Seeger, A., and Schlieker, H., Entry of Escherichia coli into Stationary Phase Is Indicated by Endogenous and Exogenous Accumulation of Nucleobases, Appl. Environ. Microbiol., 1995, vol. 61, no. 12, pp. 4147–4151.

    PubMed  CAS  Google Scholar 

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Original Russian Text © N.P. Zakataeva, E.A. Kutukova, S.V. Gronskiy, P.V. Troshin, V.A. Livshits, V.V. Aleshin, 2006, published in Mikrobiologiya, 2006, Vol. 75, No. 4, pp. 509–520.

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Zakataeva, N.P., Kutukova, E.A., Gronskiy, S.V. et al. Export of metabolites by the proteins of the DMT and RhtB families and its possible role in intercellular communication. Microbiology 75, 438–448 (2006). https://doi.org/10.1134/S0026261706040126

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