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.

  • Letter
  • Published:

Sensitization of Gram-negative bacteria to antibiotics and complement by a nontoxic oligopeptide

Abstract

A major virulence factor of bacteria that cause generalized infections is their resistance to the lytic action of the complement cascade1, an important defence mechanism of the host. Invasive Gram-negative enteric bacteria, which cause about one-third of all bacteraemic infections2,3, are completely resistant to lysis by complement, even in the presence of hyperim-mune serum4–6. The same bacteria are also resistant to many antibiotics that are effective therapeutic agents against other bacteria, as the outermost surface layer (the outer membrane) of the bacteria functions as a permeability barrier7. Here we show that it is possible to sensitize such bacteria to both complement and antibiotics by using an agent that binds to the outer membrane. This agent is a nontoxic derivative of polymyxin which by itself has no bactericidal action8,9.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Fine, D. P. Complement and Infectious Diseases, 157 (CRC, Boca Raton, Florida, 1981).

    Google Scholar 

  2. McCowan, J. E. Jr, Barnes, M. W. & Finland, M. J. infect. Dis. 132, 316–334 (1975).

    Article  Google Scholar 

  3. Williams, G. T., Houang, E. T., Shaw, E. J. & Tabaqchali, S. Lancet ii, 1291–1293 (1976).

    Article  Google Scholar 

  4. Roantree, R. J. & Ranz, L. A. J. clin. Invest. 39, 72–81 (1960).

    Article  CAS  Google Scholar 

  5. Roantree, R. J. & Poppas, N. C. J. clin. Invest. 39, 82–91 (1960).

    Article  CAS  Google Scholar 

  6. Joiner, K. A., Hammer, C. H., Brown, E. J., Cole, R. J. & Frank, M. M. J. exp. Med. 155, 797–808 (1982).

    Article  CAS  Google Scholar 

  7. Nikaido, H. & Nakae, T. Adv. microb. Physiol. 20, 163–250 (1979).

    Article  CAS  Google Scholar 

  8. Chihara, S., Tobita, T., Yahata, M., Ito, A. & Koyama, Y. Agric. Biol. Chem. 37, 2455–2463 (1973).

    CAS  Google Scholar 

  9. Chihara, S., Ito, A., Yahata, M., Tobita, T. & Koyama, Y. Agric. Biol. Chem. 38, 521–529 (1974).

    Article  CAS  Google Scholar 

  10. Teuber, M. & Bader, J. Archs Microbiol. 109, 51–58 (1976).

    Article  CAS  Google Scholar 

  11. Teuber, M. Archs Microbiol. 100, 131–144 (1974).

    Article  CAS  Google Scholar 

  12. Rosenthal, K. & Storm, D. J. Antibiot. 30, 1087–1092 (1977).

    Article  CAS  Google Scholar 

  13. Vaara, M. & Vaara, T. Antimicrob. Ag. Chemother. 19, 578–583 (1981).

    Article  CAS  Google Scholar 

  14. Vaara, M. J. Bact. 148, 426–434 (1981).

    Article  CAS  Google Scholar 

  15. Storm, D. E., Rosenthal, K. S. & Swanson, P. E. A. Rev. Biochem. 46, 723–763 (1977).

    Article  CAS  Google Scholar 

  16. Kunin, C. M. J. infect. Dis. 121, 55–65 (1960).

    Article  Google Scholar 

  17. Garrod, L. P., Lambert, H. P. & O'Grady, F. Antibiotic and Chemotherapy (Churchill Livingstone, London, 1981).

    Google Scholar 

  18. Paakkanen, J., Gotschlich, E. C. & Mäkelä, P. H. J. Bact. 139, 835–841 (1979).

    Article  CAS  Google Scholar 

  19. Vaara, M. thesis, Univ. Helsinki, (1981).

  20. Leive, L. Ann. N.Y. Acad. Sci. 235, 109–127 (1974).

    Article  ADS  CAS  Google Scholar 

  21. Leive, L. & Kollin, V. Biochem. biophys. Res. Commun. 28, 229–236 (1967).

    Article  CAS  Google Scholar 

  22. Podack, E. R. & Müller-Eberhard, H. J. J. Immun. 121, 1025–1030 (1978).

    CAS  PubMed  Google Scholar 

  23. Joiner, K. A., Hammer, C. H., Brown, E. J. & Frank, M. M. J. exp. Med. 155, 809–819 (1982).

    Article  CAS  Google Scholar 

  24. Sanderson, K. E., Ross, H., Ziegler, L. & Mäkelä, P. H. Bact. Rev. 36, 608–637 (1972).

    CAS  PubMed  Google Scholar 

  25. Keleti, G. & Lederer, W. H. Handbook of Micromethods for the Biological Sciences (Van Nostrand, New York, 1974).

    Google Scholar 

  26. Miller, J. H. Experiments in Molecular Genetics (Cold Spring Harbor Laboratory, New York, 1972).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vaara, M., Vaara, T. Sensitization of Gram-negative bacteria to antibiotics and complement by a nontoxic oligopeptide. Nature 303, 526–528 (1983). https://doi.org/10.1038/303526a0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/303526a0

This article is cited by

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