Abstract
Tetracycline resistance genes are widespread among gram-negative aerobic bacteria. A large number of independent isolates have been characterized and most of them shown to belong to five different classes of determinants, named classes A to E. They are usually plasmid- or transposon-encoded and share several genetic and mechanistic features (Chopra et al., 1981; Izaki et al., 1966; Levy and McMurray, 1978; Mendez et al., 1980; Marshall et al., 1986; Levy, 1988). Resistance against the drug is achieved by an active export mechanism of tetracycline from the resistant cell. This is mediated by a membrane associated resistance protein (McMurray et al., 1980; Waters et al., 1983; Hillen and Schollmeier, 1983; Nguyen et al., 1983). The expression of this protein is inducible by subinhibitory amounts of tetracycline (Mendez et al., 1980). This regulation of expression occurs at the level of transcription. It is brought about by a repressor protein, which under non-inducing conditions represses expression of the resistance gene, as well as that of its own gene. Induction of tetracycline resistance is achieved by binding of tetracycline to the repressor, thereby inactivating the operator-binding function of the protein and allowing expression of both genes. The regulated genes termed tetA for resistance and tetR for repressor are arranged adjacent to each other with opposite polarity and share common regulatory sequences comprising at least two promotors and two operators per determinant (Beck et al., 1982; Wray et al., 1981; Jorgensen and Reznikoff, 1979; Hillen et al., 1984; Hillen et al., 1982a; Bertrand et al., 1983; Altenbuchner et al., 1983; Unger et al., 1984a; Unger et al., 1984b; Tovar et al., 1988).
Preview
Unable to display preview. Download preview PDF.
References
Altenbuchner, J., Schmid, K. and Schmitt, R. (1983). Tn1721-encoded tetracycline resistance: mapping of structural and regulatory genes mediating resistance. J. Bacteriol., 153, 116–123
Altschmied, L. and Hillen, W. (1984). Tet repressor-tet operator complex formation induces conformational changes in the tet operator DNA. Nucl. Acids Res., 12, 2171–2180
Altschmied, L., Baumeister, R., Pfleiderer, K. and Hillen, W. (1988). A threonine to alanine exchange at position 40 of Tet repressor alters the recognition of the sixth base pair of tet operator from GC to AT. EMBO J., 7, 4011–4017
Beck, C. F., Mutzel, R., Barbe, J. and Müller, W. (1982). A multifunctional gene (tetR) controls Tn10-encoded tetracycline resistance. J. Bacteriol., 150, 633–642
Berg, O.G. and von Hippel. P. H. (1985). Diffusion-controlled macromolecular interactions. Ann. Rev. Biophys. Chem., 14, 131–160
Bertrand, K. P., Postle, K., Wray, L. V., Jr and Reznikoff, W. S. (1983). Overlapping divergent promoters control expression of Tn10 tetracycline resistance. Gene, 23, 149–156
Chopra, I., Howe, T. G. B., Linton, A. H., Linton, K. B., Richmond, M. H. and Spelber, D. C. E. (1981). The tetracyclines: prospects at the beginning of the 1980s. J. Antimicrob. Chemother., 5, 5–21
Ebright, R. H. (1986). Proposed amino acid-base pair contacts for 13 sequence-specific DNA binding proteins. Protein Structure, Folding, and Design. In UCLA Symposia on Molecular and Cellular Biology, Vol. 39 (Oxender, D. L., ed.), Liss, New York, 207–219
Epe, B. and Woolley, P. (1984). The binding of 6-demethylchlortetracycline to 70S, 50S, and 30S ribosome particles: a quantitative study by fluorescence anisotropy. EMBO J., 3, 119–126
Hansen, D., Altschmied, L. and Hillen, W. (1987). Engineered Tet repressor mutants with single tryptophan residues as fluorescent probes. J. Biol. Chem., 262, 14030–14035
Hansen, D. and Hillen, W. (1987). Tryptophan in α-helix 3 of Tet repressor forms a sequence-specific contact with tet operator in solution. J. Biol. Chem., 262, 12269–12275
Helene, C. and Dimicoli, J. (1972). Interaction of oligopeptides containing aromatic amino acids with nucleic acids. Fluorescence and proton magnetic resonance studies. FEBS Lett., 26, 6–10
Hershfield, V., Boyer, H. W., Chow, L. and Helinski, D. R. (1976). Characterization of a mini-ColEl plasmid. J. Bacteriol., 126, 447–453
Hever, C. and Hillen, W. (1988). Tet repressor-tet operator contacts probed by operator DNA-modification interference studies. J. Mol. Biol., 202, 407–415
Hillen, W., Gatz, C., Altschmied, L., Schollmeier, K. and Meier, I. (1983). Control of expression of the Tn10-encoded tetracycline resistance genes: equilibrium and kinetic investigation of the regulatory reactions. J. Mol. Biol., 169, 707–722
Hillen, W., Klock, G., Kaffenberger, L., Wray, L. V., Jr and Reznikoff, W. S. (1982a). Purification of the Tet repressor and tet operator from the transposon Tn10 and characterization of their interaction. J. Biol. Chem., 257, 6605–6613
Hillen, W., Klein, R. B. and Wells, R. D. (1981). Preparation of milligram amounts of 21 deoxyribonucleic acid restriction fragments. Biochemistry, 20, 3748–3756
Hillen, W. and Schollmeier, K. (1983). Nucleotide sequence of the Tn10 encoded tetracycline resistance gene. Nucl. Acids Res., 11, 525–539
Hillen, W., Schollmeier, K. and Gatz, C. (1984). Control of expression of the Tn10-encoded tetracycline resistance gene. II. Interaction of RNA polymerase and Tet repressor with the tet operon regulatory region. J. Mol. Biol., 172, 185–201
Hillen, W., Unger, B. and Klock, G. (1982b). Analysis of tet operator-Tet repressor complexes by thermal denaturation studies. Nucl. Acids Res., 10, 6085–6097
Hillen, W. and Unger, B. (1982). Binding of four repressors to double-stranded tet operator region stabilizes it against thermal denaturation. Nature, 297, 700–702
Hochschild, A. and Ptashne, M. (1986). Cooperative binding of λ repressors to sites separated by integral turns of the DNA helix. Cell, 44, 681–687
Isackson, P. J. and Bertrand, K. P. (1985). Dominant negative mutations in the Ta10 Tet repressor. Evidence for use of the conserved helix-turn-helix motif in DNA binding. Proc. Natl Acad. Sci. USA, 82, 6226–6230
Izaki, K., Kiuchi, K. and Arima, K. (1966). Specificity and mechanism of tetracycline resistance in a multiple drug resistant strain of Escherichia coli. J. Bacteriol., 91, 628–633
Jorgensen, R. A. and Reznikoff, W. S. (1979). Organization of structural and regulatory genes that mediate tetracycline resistance in transposon Tn10. J. Bacteriol., 138, 705–714
Kleinschmidt, C., Tovar, K., Hillen, W. and Pörschke, D. (1988). Dynamics of a Repressor-Operator Recognition: the Tn10 encoded tetracycline resistance control. Biochemistry, 27, 1094–1104
Klock, G. and Hillen, W. (1986). Expression, purification and operator binding of the transposon Tn1721-encoded Tet repressor. J. Mol. Biol., 189, 633–641
Klock, G., Unger, B., Gatz, C., Hillen, W., Altenbuchner, J., Schmid, K. and Schmitt, R. (1985). Heterologous repressor-operator recognition among four classes of tetracycline resistance determinants. J. Bacteriol., 161, 326–332
Lederer, H. Tovar, K., Baer, G., May, R. P., Hillen, W. and Heumann, H. (1989). The quaternary structure of Tet repressors bound to the Tn10 encoded tet gene control region determined by neutron solution scattering. EMBO J., in the press
Levy, S. B. and McMurray, L. (1978). Plasmid-determined tetracycline resistance involves new transport systems for tetracycline. Nature, 275, 90–92
Levy, S. B. (1988). Tetracycline resistance determinants are widespread. ASM News, 54, 418–421
Little, J. W., Edmiston, S. H., Pacelli, L. Z. and Mount, D. W. (1980). Cleavage of the Escherichia coli lexA protein by the recA protease. Proc. Natl Acad. Sci. USA, 77, 3225–3229
Liu-Johnson, H-N., Gartenberg, M. R. and Crothers, D. M. (1986). The DNA bending domain and bending angle of E. coli CAP protein. Cell, 47, 681–687
McMurray, L., Petrucci, R. E. and Levy, S. B. (1980). Active efflux of tetracycline encoded by four genetically different resistance determinants in Escherichia coli. Proc. Natl Acad. Sci. USA, 77, 3974–3977
Marshall, B., Morrisey, S., Flynn, P. and Levy, S. B. (1986). A new tetracycline resistance determinant, class E, Isolated from Enterobacteriaceae. Gene, 50, 111–117
Meier, I., Wray, L. V., Jr and Hillen, W. (1988). Differential regulation of the Tn10 encoded tetracycline resistance genes tetA and tetR by the tandem tet operators O1 and O2. EMBO J., 7, 567–572
Mendez, B., Tachibana, C. and Levy, S. B. (1980). Heterogeneity of tetracycline resistance determinants. Plasmid, 3, 99–108
Nguyen, T. T., Postle, K. and Bertrand, K. P. (1983). Sequence homology between the tetracycline resistance determinants of Tn10 and pBR322. Gene, 25, 83–92
Oemichen, R., Klock, G., Altschmied, L. and Hillen, W. (1984). Construction of an E. coli strain overproducing the Tn10-encoded TET repressor and its use for large scale purification. EMBO J., 3, 539–543
Ohlendorf, D. H., Anderson, W. F., Lewis, M., Pabo, C. O. and Matthews, B. W. (1983). Comparison of the structures of Cro and λ repressor proteins from bacteriophage λ. J. Mol. Biol., 169, 757–769
Pabo, C. O. and Sauer, R. T. (1984). Protein-DNA recognition. Ann. Rev. Biochem., 53, 293–321
Pörschke, D. and Ronnenberg, J. (1981). The reaction of aromatic peptides with double helical DNA. Quantitative characterization of a two step reaction scheme. Biophys. Chem., 13, 283–290
Pörschke, D., Tovar, K. and Antosiewicz, J. (1988). Structure of the Tet repressor-operator complexes in solution from electrooptical measurements and hydrodynamic simulations. Biochemistry, 27, 4674–4679
Postle, K., Nguyen, T. T. and Bertrand, K. P. (1984). Nucleotide sequence of the repressor gene of the Tn10 tetracycline resistance determinant. Nucl. Acids Res., 12, 4849–4863
Ptashne, M., Backman, K., Humayun, M. Z., Jeffrey, A., Maurer, R., Meyer, B. and Sauer, R. T. (1976). Autoregulation and function of a repressor in bacteriophage lambda. Science, 194, 156–161
Ptashne, M., Jeffrey, A., Johnson, A. D., Maurer, R., Meyer, B. J., Pabo, C. O., Roberts, T. M. and Sauer, R. T. (1980). How the λ repressor and cro work. Cell, 19, 1–11
Roberts, J. W. and Roberts, C. W. (1975). Proteolytic cleavage of bacteriophage lambda repressor in induction. Proc. Natl Acad. Sci. USA, 72, 147–159
Sauer, R. T., Yocum, R. R., Doolittle, R. F., Lewis, M. and Pabo, C. O. (1982). Homology among DNA-binding proteins suggests use of a conserved super-secondary structure. Nature, 298, 447–451
Schevitz, R. W., Otwinowski, Z., Joachimiak, A., Lawson, C. L. and Sigler, P. B. (1985). The three-dimensional structure of trp repressor. Nature, 317, 782–786
Seeman, N. C., Rosenberg, J. M. and Rich, A. (1976). Sequence-specific recognition of double helical nucleic acids by proteins. Proc. Natl Acad. Sci. USA, 73, 804–808
Takahashi, M., Altschmied, L. and Hillen, W. (1986). Kinetic and equilibrium characterization of the Tet repressor-tetracycline complex by fluorescence measurements. J. Mol. Biol., 107, 341–348
Tovar, K., Ernst, A. and Hillen, W. (1988). Identification and nucleotide sequence of the class E tet regulatory elements and operator and inducer binding of the encoded purified Tet repressor. Mol. Gen. Genet., 215, 76–80
Unger, B., Becker, J. and Hillen, W. (1984a). Nucleotide sequence of the gene, protein purification and characterization of the pSC101-encoded tetracycline resistance-gene-repressor. Gene, 31, 103–108
Unger, B., Klock, G. and Hillen, W. (1984b). Nucleotide sequence of the repressor gene of the RA1 tetracycline resistance determinant: structural and functional comparison with three related Tet repressor genes. Nucl. Acids Res., 12, 7693–7703
Wagenhöfer, M., Hansen, D. and Hillen, W. (1988). Thermal denaturation of engineered Tet repressor proteins and their complexes with tet operator and tetracycline studied by temperature gradient gel electrophoresis. Ann. Biochem., 175, 422–432
Waters, S., Rogowsky, P., Grinsted, J., Altenbuchner, J. and Schmitt, R. (1983). The tetracycline resistance determinants of RP1 and Tn1721: nucleotide sequence analysis. Nucl. Acids Res., 11, 6089–6105
Weber, K. and Geisler, N. (1978). lac repressor fragments produced in vivo and in vitro: an approach to the understanding of the interaction of repressor and DNA. In The Operon, Reznikoff, W. S. and Miller, J. (eds), Cold Spring Harbour Laboratory Press, New York, 155–175
Wells, R. D., Goodman, T. C., Hillen, W., Horn, G. T., Klein, R. D., Larson, J. E., Müller, U. R., Neuendorf, S. K., Panayotatos, N. and Stirdivant, S. M. (1980). Prog. Nucl. Acids Res. Molec. Biol., 24, 167–267
Wissmann, A., Meier, I. and Hillen, W. (1988). Saturation mutagenesis of the Tn10-encoded tet operator O1: identification of base pairs involved in Tet repressor recognition. J.Mol. Biol., 202, 397–406
Wray, L. V., Jr, Jorgensen, R. A. and Reznikoff, W. S. (1981). Identification of the tetracycline resistance promoter and repressor in transposon Tn10. J. Bacteriol., 147, 297–304
Wray, L. V., Jr and Reznikoff, W. S. (1983). Identification of repressor binding sites controlling expression of tetracycline resistance encoded by Tn10. J. Bacteriol., 156, 1188–1191
Zhang, R-G., Joachimiak, A., Lawson, C. L., Schevitz, R. W., Otwinowski, Z. and Sigler, P. B. (1987). The crystal structure of trp aporepressor at 1.8 Å shows how binding tryptophan enhances DNA affinity. Nature, 327, 591–597
Editor information
Editors and Affiliations
Copyright information
© 1989 The Contributors
About this chapter
Cite this chapter
Hillen, W., Wissmann, A. (1989). Tet repressor-tet operator interaction. In: Saenger, W., Heinemann, U. (eds) Protein-Nucleic Acid Interaction. Topics in Molecular and Structural Biology. Palgrave, London. https://doi.org/10.1007/978-1-349-09871-2_7
Download citation
DOI: https://doi.org/10.1007/978-1-349-09871-2_7
Publisher Name: Palgrave, London
Print ISBN: 978-1-349-09873-6
Online ISBN: 978-1-349-09871-2
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)