Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Plasmid-determined tetracycline resistance involves new transport systems for tetracycline

Abstract

TETRACYCLINES are broad-spectrum bacteriostatic antibiotics which act by inhibiting protein synthesis1,2. However, their usefulness in combating bacterial infection has been sharply curtailed by the widespread occurrence in bacteria of tetracycline resistance encoded by genes located on extrachromosomal DNA elements called plasmids3,4. In many bacteria, notably Enterobacteriaceae, Pseudomonas and Staphylococcus, plasmid-mediated tetracycline resistance is inducible; the resistance level can be increased by preincubation of the cells in sub-inhibitory amounts of tetracycline5–8. Coincident with induced resistance is the induced synthesis of a plasmid-encoded inner membrane protein which we have designated TET protein8–10. Synthesis of this protein (and presumably most of the resistance determinant) is negatively regulated; a represser has been partially purified11. However, the mechanisms for plasmid-mediated tetracycline resistance are not yet clear, and there seems to be no degradation of the antibiotic in resistant cells10,12,13. Although resistant cells accumulate less tetracycline than do sensitive cells14,15, the moderately reduced uptake does not explain the much larger difference in sensitivity to the drug10,16,17. We report here that plasmid-containing resistant cells take up tetracycline by a different transport mechanism from that of sensitive cells. This altered transport seems to be responsible for at least part of the difference in tetracycline inhibition of sensitive as compared to resistant cells.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

References

  1. Suzuki, I., Kaji, H. & Kaji, A. Proc. natn. Acad. Sci. U.S.A. 55, 1483–1490 (1966).

    ADS  Article  Google Scholar 

  2. Högenauer, G. & Turnowsky, F. FEBS Lett. 26, 185–188 (1972).

    Article  PubMed  Google Scholar 

  3. Watanabe, T. Bact. Rev. 27, 87–115 (1963).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Falkow, S. Infectious Multiple Drug Resistance (Pion, London, 1975).

    Book  Google Scholar 

  5. Izaki, K., Kiuchi, K. & Arima, K. J. Bact. 91, 628–633 (1966).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Unowsky, J. & Rachmeler, M. J. Bact. 92, 358–365 (1966).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Franklin, T. J. Biochem. J. 105, 371–378 (1967).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. Levy, S. B. & McMurry, L. Biochem. biophys. Res. Commun. 56, 1060–1068 (1974).

    CAS  Article  PubMed  Google Scholar 

  9. Levy, S. B. in Drug-inactivating Enzymes and Antibiotic Resistance (eds Mitsuhashi, Rosival & Krčméry) 215–225 (Springer, Berlin, 1975).

    Book  Google Scholar 

  10. Levy, S. B., McMurry, L., Onigman, P. & Saunders, R. M. in Topics in Infectious Diseases, Vol. 2 (eds Drews & Högenauer) 180–203 (Springer, Berlin, 1977).

    Google Scholar 

  11. Yang, H-L., Zubay, G. & Levy, S. B. Proc. natn. Acad. Sci. U.S.A. 73, 1509–1512 (1976).

    ADS  CAS  Article  Google Scholar 

  12. DeZeeuw, J. R. J. Bact. 95, 498–506 (1968).

    CAS  Google Scholar 

  13. Sompolinsky, D., Krawitz, T., Zaidenzaig, Y. & Abramova, N. J. gen. Microbiol. 62, 341–349 (1970).

    CAS  Article  PubMed  Google Scholar 

  14. Arima, K. & Izaki, K. Nature 200, 192–193 (1963).

    ADS  CAS  Article  PubMed  Google Scholar 

  15. Franklin, T. J. & Godfrey, A. Biochem. J. 94, 54–60 (1965).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Reynard, A. M., Nellis, L. F. & Beck, M. E. Appl. Microbiol. 21, 71–75 (1971).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Levy, S. B. & McMurry, L. in Microbiology 1978 (ed. Schlessinger) 177–180 (Am. Soc. for Microbiol., Washington, 1978).

    Google Scholar 

  18. McMurry, L. & Levy, S. B. Antimicrob. Ag. Chem. 14, 201–209 (1978).

    CAS  Article  Google Scholar 

  19. Foster, T. J., Howe, T. G. B. & Richmond, K. M. V. J. Bact. 124, 1153–1158 (1975).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Lehninger, A. L. Biochemistry, 429 (North, New York, 1975).

    Google Scholar 

  21. Berger, E. A. & Heppel, L. A. J. biol. Chem. 249, 7747–7755 (1974).

    CAS  PubMed  Google Scholar 

  22. Wilson, D. B. J. Bact. 126, 1156–1165 (1976).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Levy, S. B. J. Bact. 108, 300–308 (Fig. 4) (1971).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Lennox, E. S. Virology 1, 190–206 (1955).

    CAS  Article  PubMed  Google Scholar 

  25. Curtiss, R. J. Bact. 89, 28–40 (1965).

    PubMed Central  Google Scholar 

  26. Heppel, L. A. in Structure and Function of Biological Membranes (ed. Rothfield) 223–247 (Academic, New York, 1971).

    Book  Google Scholar 

  27. Navashin, S. M., Beliavskaya, I. V., Sazykin, Y. O. & Gryaznova, N. S. in Drug-inactivating Enzymes and Antibiotic Resistance (eds Mitsuhashi, Rosival & Krčméry), 227–230 (Springer, Berlin, 1975).

    Book  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

LEVY, S., MCMURRY, L. Plasmid-determined tetracycline resistance involves new transport systems for tetracycline. Nature 276, 90–92 (1978). https://doi.org/10.1038/276090a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/276090a0

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing