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Gene Review

tetA  -  similar to protein family HMM PF07690

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].
  • The first resistance determinant, cloned as a 4,590-bp fragment, was identical to tetA and flanking sequences encoded on transposon Tn10 from Shigella flexneri [2].
  • The pp-tet was highly homologous to the tet(D) of plasmid RA1 isolated from Aeromonas hydrophila with two nucleotide differences in the tetR, and of plasmid pIP173 from Salmonella ordonez with two nucleotide differences in the tetA [3].
  • The pAB124 tet determinant differed from the tetA through tetD determinants found in gram-negative bacteria in DNA-DNA hybridization and in the ability to prevent accumulation of different tetracycline derivatives, but was closely related to the tet determinant of another plasmid isolated from Bacillus species, pBC16 [4].
  • The two recombinant phages are convenient delivery vehicles which permit the in vivo substitution of the tetA locus of any Tn10 insertion with the Tes or the Tek fragment [5].

High impact information on tetA


Chemical compound and disease context of tetA


Biological context of tetA

  • Based on the deduced amino acid sequence, the tetA proteins of RP1/Tn1721 are 78% homologous with that of pBR322 and 45% homologous with that of Tn10 [14].
  • Two open reading frames of divergent polarity have been assigned to a regulatory gene (tetR) and a gene encoding a resistance protein (tetA) [14].
  • We determined the nucleotide sequence of the class E tetA gene on plasmid pSL1456 from Escherichia coli SLH1456A [11].
  • Complementation occurred between promoter-proximal tet point mutations and distal tet::Tn5 insertions, suggesting the existence of two structural genes, tetA and tetB [15].
  • These results, together with the analysis of polypeptides in minicells harboring pDU938tet::Tn5 mutants, suggested that tetA and tetB are expressed coordinately in an operon [15].

Anatomical context of tetA

  • The tetB gene encodes the previously characterized 36,000-dalton cytoplasmic membrane TET protein, but the product of tetA was not identified [15].

Associations of tetA with chemical compounds

  • While the repressive effect of the TetR protein from strain C58 (TetRC58) on the tetA gene from strain RP4 (tetARP4) was not relieved by tetracycline, repression of tetAC58 by TetRRP4 was lifted by this antibiotic [16].
  • In the Tet(B)-containing vesicle study, tigecycline did not significantly inhibit tetracycline efflux-coupled proton translocation and at 10 microM did not cause proton translocation [17].
  • Fe(2+)-tetracycline-mediated cleavage of the Tn10 tetracycline efflux protein TetA reveals a substrate binding site near glutamine 225 in transmembrane helix 7 [18].
  • The enhanced gyrase cleavage also required translation; chloramphenicol treatment or the insertion of a translation terminator within the 5'-proximal region of the tetA gene abolished the enhanced cleavage [19].
  • Doxycycline was the most effective inducer of tetA gene expression [20].

Other interactions of tetA

  • The direction of transcription is opposite to that of neighboring gene tetA, which encodes the TetA protein [21].
  • Subcloning, transposon mutagenesis, and DNA sequence analysis revealed that this DNA fragment contained two divergently transcribed genes, tetA and tetR, encoding products that were very similar to proteins of the Tet(A) class of tetracycline resistance systems [16].
  • It contains three 38-bp inverted repeats, and (in this order) a new orfI, a resolution site (res), genes encoding resolvase (tnpR), transposase (tnpA), tetracycline-resistance (TcR) repressor (tetR), TcR (tetA) and a truncated transposase gene (tnpA') [22].
  • On pBR322 DNA, gyrase cleavage sites were concentrated in the region between the 3'-ends of the tetA and bla genes [19].
  • The structural genes for tetA, the Tn10 tetracycline-resistance function, and for tetR, the Tn10 tet repressor, are transcribed in opposite directions from promoters in a regulatory region located between the two structural genes [23].

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. Genetic determinants of tetracycline resistance in Vibrio harveyi. Teo, J.W., Tan, T.M., Poh, C.L. Antimicrob. Agents Chemother. (2002) [Pubmed]
  3. The transposon-like structure of IS26-tetracycline, and kanamycin resistance determinant derived from transferable R plasmid of fish pathogen, Pasteurella piscicida. Kim, E.H., Aoki, T. Microbiol. Immunol. (1994) [Pubmed]
  4. Biochemical and genetic characterization of the tet determinant of Bacillus plasmid pAB124. Eccles, S.J., Chopra, I. J. Bacteriol. (1984) [Pubmed]
  5. A system for in vivo selection of genomic rearrangements with predetermined endpoints in Escherichia coli using modified Tn10 transposons. François, V., Louarn, J., Patte, J., Louaran, J.M. Gene (1987) [Pubmed]
  6. Modulation of tyrT promoter activity by template supercoiling in vivo. Bowater, R.P., Chen, D., Lilley, D.M. EMBO J. (1994) [Pubmed]
  7. Selection of biocatalysts for chemical synthesis. van Sint Fiet, S., van Beilen, J.B., Witholt, B. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  8. Transposon stability and a role for conjugational transfer in adaptive mutability. Godoy, V.G., Fox, M.S. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  9. Second-site suppressor mutations for the serine 202 to phenylalanine substitution within the interdomain loop of the tetracycline efflux protein Tet(C). Sapunaric, F.M., Levy, S.B. J. Biol. Chem. (2003) [Pubmed]
  10. 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]
  11. 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]
  12. Overview of bacterial expression systems for heterologous protein production: from molecular and biochemical fundamentals to commercial systems. Terpe, K. Appl. Microbiol. Biotechnol. (2006) [Pubmed]
  13. Decreased function of the class B tetracycline efflux protein Tet with mutations at aspartate 15, a putative intramembrane residue. McMurry, L.M., Stephan, M., Levy, S.B. J. Bacteriol. (1992) [Pubmed]
  14. The tetracycline resistance determinants of RP1 and Tn1721: nucleotide sequence analysis. Waters, S.H., Rogowsky, P., Grinsted, J., Altenbuchner, J., Schmitt, R. Nucleic Acids Res. (1983) [Pubmed]
  15. 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]
  16. Cloning and characterization of a tetracycline resistance determinant present in Agrobacterium tumefaciens C58. Luo, Z.Q., Farrand, S.K. J. Bacteriol. (1999) [Pubmed]
  17. Effects of efflux transporter genes on susceptibility of Escherichia coli to tigecycline (GAR-936). Hirata, T., Saito, A., Nishino, K., Tamura, N., Yamaguchi, A. Antimicrob. Agents Chemother. (2004) [Pubmed]
  18. 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]
  19. Effects of transcription and translation on gyrase-mediated DNA cleavage in Escherichia coli. Koo, H.S., Wu, H.Y., Liu, L.F. J. Biol. Chem. (1990) [Pubmed]
  20. Resistance to various tetracyclines mediated by transposon Tn10 in Escherichia coli K-12. Traub, B., Beck, C.F. Antimicrob. Agents Chemother. (1985) [Pubmed]
  21. A multifunctional gene (tetR) controls Tn10-encoded tetracycline resistance. Beck, C.F., Mutzel, R., Barbé, J., Müller, W. J. Bacteriol. (1982) [Pubmed]
  22. Complete nucleotide sequence of Tn1721: gene organization and a novel gene product with features of a chemotaxis protein. Allmeier, H., Cresnar, B., Greck, M., Schmitt, R. Gene (1992) [Pubmed]
  23. Overlapping divergent promoters control expression of Tn10 tetracycline resistance. Bertrand, K.P., Postle, K., Wray, L.V., Reznikoff, W.S. Gene (1983) [Pubmed]
  24. Frequency and distribution of tetracycline resistance genes in genetically diverse, nonselected, and nonclinical Escherichia coli strains isolated from diverse human and animal sources. Bryan, A., Shapir, N., Sadowsky, M.J. Appl. Environ. Microbiol. (2004) [Pubmed]
  25. Glutamate residues located within putative transmembrane helices are essential for TetA(P)-mediated tetracycline efflux. Kennan, R.M., McMurry, L.M., Levy, S.B., Rood, J.I. J. Bacteriol. (1997) [Pubmed]
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