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Gene Review

tetA  -  TetA

Escherichia coli

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Disease relevance of tetA

  • Potential silencing of the resistance genes bla(OXA-2), aadA1, sul1, and tetA carried on the plasmid pVE46 in a recent porcine isolate of Escherichia coli was investigated following oral inoculation of the strain into organic piglets [1].
  • Screens were designed based upon fusions with three antibiotic induced promoters: the tetracycline induced tetA/tetR promoter from transposon Tn10, the erythromycin induced promoter from the Staphylococcus aureus ermC erythromycin-resistance gene and the chloramphenicol induced promoter from the S. aureus cat86 chloramphenicol-resistance gene [2].
  • On the promoter side, the main features of the L: -arabinose inducible araBAD promoter (P(BAD)), the lac promoter, the L: -rhamnose inducible rhaP ( BAD ) promoter, the T7 RNA polymerase promoter, the trc and tac promoter, the lambda phage promoter p ( L ), and the anhydrotetracycline-inducible tetA promoter/operator are summarized [3].
  • Some sequence elements in this novel membrane protein share similarity to regions in the transposon Tn10-encoded tetracycline resistance determinant TetA, the multidrug transporter Bmr from Bacillus subtilis, and the bicyclomycin resistance determinant Bcr from E. coli [4].
  • Hydrophilicity plots of BaiG show a high degree of similarity to class K and L TetA proteins from gram-positive bacteria, and, like these classes of TetA proteins, BaiG has 14 proposed transmembrane domains [5].

High impact information on tetA


Chemical compound and disease context of tetA


Biological context of tetA


Anatomical context of tetA

  • For this to occur on a plasmid, we have shown that the transcribing RNA polymerase must be anchored to the cell membrane by transcription, translation, and export of the tetA gene and that the cell background must be topA [16].
  • Spheroplasts and inside-out vesicles of the TetA protein synthesizing maxicells were subjected to limited digestion by proteases of different specificities [17].

Associations of tetA with chemical compounds

  • The tetracycline resistance determinant in transposon Tn10 consists of two genes, the tetA resistance gene and the tetR repressor gene, that are transcribed from divergent overlapping promoters [18].
  • Addition of the inducer 5a,6-anhydrotetracycline results in a 270- to 430-fold increase in tetA mRNA and a 35- to 65-fold increase in tetR mRNA [18].
  • An aspartate residue in the 8-9 loop that has no counterpart in LacY and TetA, but is conserved among members of the aromatic acid/H(+) symporter family of the MFS, was found to be critical for 4-HBA transport [19].
  • We found that, when chelated to tetracycline, Fe(2+) cleaved the backbone of TetA predominantly at a single position, glutamine 225 in transmembrane helix 7 [20].
  • Since alpha-methylglucoside transport was not affected, the overproduced TetA protein may cause not destruction of membrane structure but rather unrestricted translocation of protons and/or ions across the membrane [21].

Analytical, diagnostic and therapeutic context of tetA


  1. Evidence of antibiotic resistance gene silencing in Escherichia coli. Enne, V.I., Delsol, A.A., Roe, J.M., Bennett, P.M. Antimicrob. Agents Chemother. (2006) [Pubmed]
  2. The use of beta-galactosidase gene fusions to screen for antibacterial antibiotics. Kirsch, D.R., Lai, M.H., McCullough, J., Gillum, A.M. J. Antibiot. (1991) [Pubmed]
  3. Overview of bacterial expression systems for heterologous protein production: from molecular and biochemical fundamentals to commercial systems. Terpe, K. Appl. Microbiol. Biotechnol. (2006) [Pubmed]
  4. The Lactococcal lmrP gene encodes a proton motive force-dependent drug transporter. Bolhuis, H., Poelarends, G., van Veen, H.W., Poolman, B., Driessen, A.J., Konings, W.N. J. Biol. Chem. (1995) [Pubmed]
  5. Sequencing and expression of a gene encoding a bile acid transporter from Eubacterium sp. strain VPI 12708. Mallonee, D.H., Hylemon, P.B. J. Bacteriol. (1996) [Pubmed]
  6. Differential regulation of the Tn10-encoded tetracycline resistance genes tetA and tetR by the tandem tet operators O1 and O2. Meier, I., Wray, L.V., Hillen, W. EMBO J. (1988) [Pubmed]
  7. The NH2-terminal half of the Tn10-specified tetracycline efflux protein TetA contains a dimerization domain. McMurry, L.M., Levy, S.B. J. Biol. Chem. (1995) [Pubmed]
  8. Membrane topology of the pBR322 tetracycline resistance protein. TetA-PhoA gene fusions and implications for the mechanism of TetA membrane insertion. Allard, J.D., Bertrand, K.P. J. Biol. Chem. (1992) [Pubmed]
  9. Effect of DNA supercoiling and catabolite repression on the expression of the tetA genes in Escherichia coli. León, P., Alvarez, G., Díaz de León, F., Gómez-Eichelmann, M.C. Can. J. Microbiol. (1988) [Pubmed]
  10. Genetic determinants of tetracycline resistance in Vibrio harveyi. Teo, J.W., Tan, T.M., Poh, C.L. Antimicrob. Agents Chemother. (2002) [Pubmed]
  11. Analysis of tetracycline resistance encoded by transposon Tn10: deletion mapping of tetracycline-sensitive point mutations and identification of two structural genes. Coleman, D.C., Chopra, I., Shales, S.W., Howe, T.G., Foster, T.J. J. Bacteriol. (1983) [Pubmed]
  12. Sequence of a class E tetracycline resistance gene from Escherichia coli and comparison of related tetracycline efflux proteins. Allard, J.D., Bertrand, K.P. J. Bacteriol. (1993) [Pubmed]
  13. Specific stimulation of recA-independent plasmid recombination by a DNA sequence at a distance. Bi, X., Lyu, Y.L., Liu, L.F. J. Mol. Biol. (1995) [Pubmed]
  14. Substitutions in the interdomain loop of the Tn10 TetA efflux transporter alter tetracycline resistance and substrate specificity. Sapunaric, F.M., Levy, S.B. Microbiology (Reading, Engl.) (2005) [Pubmed]
  15. Structure and function of the class C tetracycline/H+ antiporter: three independent groups of phenotypes are conferred by TetA (C). Griffith, J.K., Cuellar, D.H., Fordyce, C.A., Hutchings, K.G., Mondragon, A.A. Mol. Membr. Biol. (1994) [Pubmed]
  16. Elevated unconstrained supercoiling of plasmid DNA generated by transcription and translation of the tetracycline resistance gene in eubacteria. Bowater, R.P., Chen, D., Lilley, D.M. Biochemistry (1994) [Pubmed]
  17. Topology of the transposon Tn10-encoded tetracycline resistance protein within the inner membrane of Escherichia coli. Eckert, B., Beck, C.F. J. Biol. Chem. (1989) [Pubmed]
  18. Promoter mutations affecting divergent transcription in the Tn10 tetracycline resistance determinant. Daniels, D.W., Bertrand, K.P. J. Mol. Biol. (1985) [Pubmed]
  19. Conserved cytoplasmic loops are important for both the transport and chemotaxis functions of PcaK, a protein from Pseudomonas putida with 12 membrane-spanning regions. Ditty, J.L., Harwood, C.S. J. Bacteriol. (1999) [Pubmed]
  20. Fe(2+)-tetracycline-mediated cleavage of the Tn10 tetracycline efflux protein TetA reveals a substrate binding site near glutamine 225 in transmembrane helix 7. McMurry, L.M., Aldema-Ramos, M.L., Levy, S.B. J. Bacteriol. (2002) [Pubmed]
  21. Overproduction of transposon Tn10-encoded tetracycline resistance protein results in cell death and loss of membrane potential. Eckert, B., Beck, C.F. J. Bacteriol. (1989) [Pubmed]
  22. The quarternary molecular architecture of TetA, a secondary tetracycline transporter from Escherichia coli. Yin, C.C., Aldema-Ramos, M.L., Borges-Walmsley, M.I., Taylor, R.W., Walmsley, A.R., Levy, S.B., Bullough, P.A. Mol. Microbiol. (2000) [Pubmed]
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