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.
Similar content being viewed by others
References
Fine, D. P. Complement and Infectious Diseases, 157 (CRC, Boca Raton, Florida, 1981).
McCowan, J. E. Jr, Barnes, M. W. & Finland, M. J. infect. Dis. 132, 316–334 (1975).
Williams, G. T., Houang, E. T., Shaw, E. J. & Tabaqchali, S. Lancet ii, 1291–1293 (1976).
Roantree, R. J. & Ranz, L. A. J. clin. Invest. 39, 72–81 (1960).
Roantree, R. J. & Poppas, N. C. J. clin. Invest. 39, 82–91 (1960).
Joiner, K. A., Hammer, C. H., Brown, E. J., Cole, R. J. & Frank, M. M. J. exp. Med. 155, 797–808 (1982).
Nikaido, H. & Nakae, T. Adv. microb. Physiol. 20, 163–250 (1979).
Chihara, S., Tobita, T., Yahata, M., Ito, A. & Koyama, Y. Agric. Biol. Chem. 37, 2455–2463 (1973).
Chihara, S., Ito, A., Yahata, M., Tobita, T. & Koyama, Y. Agric. Biol. Chem. 38, 521–529 (1974).
Teuber, M. & Bader, J. Archs Microbiol. 109, 51–58 (1976).
Teuber, M. Archs Microbiol. 100, 131–144 (1974).
Rosenthal, K. & Storm, D. J. Antibiot. 30, 1087–1092 (1977).
Vaara, M. & Vaara, T. Antimicrob. Ag. Chemother. 19, 578–583 (1981).
Vaara, M. J. Bact. 148, 426–434 (1981).
Storm, D. E., Rosenthal, K. S. & Swanson, P. E. A. Rev. Biochem. 46, 723–763 (1977).
Kunin, C. M. J. infect. Dis. 121, 55–65 (1960).
Garrod, L. P., Lambert, H. P. & O'Grady, F. Antibiotic and Chemotherapy (Churchill Livingstone, London, 1981).
Paakkanen, J., Gotschlich, E. C. & Mäkelä, P. H. J. Bact. 139, 835–841 (1979).
Vaara, M. thesis, Univ. Helsinki, (1981).
Leive, L. Ann. N.Y. Acad. Sci. 235, 109–127 (1974).
Leive, L. & Kollin, V. Biochem. biophys. Res. Commun. 28, 229–236 (1967).
Podack, E. R. & Müller-Eberhard, H. J. J. Immun. 121, 1025–1030 (1978).
Joiner, K. A., Hammer, C. H., Brown, E. J. & Frank, M. M. J. exp. Med. 155, 809–819 (1982).
Sanderson, K. E., Ross, H., Ziegler, L. & Mäkelä, P. H. Bact. Rev. 36, 608–637 (1972).
Keleti, G. & Lederer, W. H. Handbook of Micromethods for the Biological Sciences (Van Nostrand, New York, 1974).
Miller, J. H. Experiments in Molecular Genetics (Cold Spring Harbor Laboratory, New York, 1972).
Author information
Authors and Affiliations
Rights 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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/303526a0
- Springer Nature Limited
This article is cited by
-
A novel antibiotic combination of linezolid and polymyxin B octapeptide PBOP against clinical Pseudomonas aeruginosa strains
Annals of Clinical Microbiology and Antimicrobials (2022)
-
Causes of polymyxin treatment failure and new derivatives to fill the gap
The Journal of Antibiotics (2022)
-
Outer membrane and phospholipid composition of the target membrane affect the antimicrobial potential of first- and second-generation lipophosphonoxins
Scientific Reports (2021)
-
Design, synthesis and antimicrobial studies of some polymyxin analogues
The Journal of Antibiotics (2020)
-
Complement-dependent outer membrane perturbation sensitizes Gram-negative bacteria to Gram-positive specific antibiotics
Scientific Reports (2019)