Skip to main content
Journal of Bacteriology logoLink to Journal of Bacteriology
. 1968 Mar;95(3):1111–1117. doi: 10.1128/jb.95.3.1111-1117.1968

Accumulation in Gram-positive and Gram-negative Bacteria as a Mechanism of Resistance to Erythromycin

James C-H Mao 1, Mary Putterman 1
PMCID: PMC252138  PMID: 4966821

Abstract

Erythromycin was recovered in high yield after incubation with gram-negative bacteria. The cell-free protein-synthesizing preparation from gram-negative bacteria is equally as susceptible to the antibiotic as is that from gram-positive bacteria. Thus, neither destruction of erythromycin nor the absence of the step susceptible to the antibiotic plays an important role in the resistance mechanism of gram-negative bacteria. A 100-fold difference in accumulation of erythromycin between gram-positive and gram-negative bacteria was observed. This alone explains the resistance of gram-negative bacteria to erythromycin. Furthermore, data showed that the inhibition of growth is closely related to the accumulation of erythromycin. The concentration of intracellular erythromycin in gram-positive bacteria was found to be 44- to 90-fold greater than that of the extracellular medium. However, the antibiotic did not accumulate on the cell walls, nor was the accumulation energy-dependent. It is proposed that it takes place by the binding of erythromycin to the bacterial ribosomes, forming a very stable complex. The dissociation constants of erythromycin-Staphylococcus aureus complex and erythromycin-Bacillus subtilis complex were determined to be 1.1 × 10−7 and 3.4 × 11−7m, respectively.

Full text

PDF
1114

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. HAIGHT T. H., FINLAND M. The antibacterial action of erythromycin. Proc Soc Exp Biol Med. 1952 Oct;81(1):175–183. doi: 10.3181/00379727-81-19815. [DOI] [PubMed] [Google Scholar]
  2. HURWITZ C., ROSANO C. L. Accumulation of label from C14-streptomycin by Escherichia coli. J Bacteriol. 1962 Jun;83:1193–1201. doi: 10.1128/jb.83.6.1193-1201.1962. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. KAGAN B. M., ZOLLA S., BUSSER R., LIEPNIEKS S. SENSITIVITY OF COCCAL AND L FORMS OF STAPHYLOCOCCUS AUREUS TO FIVE ANTIBIOTICS. J Bacteriol. 1964 Sep;88:630–632. doi: 10.1128/jb.88.3.630-632.1964. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Mao J. C. Protein synthesis in a cell-free extract from Staphylococcus aureus. J Bacteriol. 1967 Jul;94(1):80–86. doi: 10.1128/jb.94.1.80-86.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Mao J. C., Tardrew P. L. Demethylation of erythromycins by rabbit tissues in vitro. Biochem Pharmacol. 1965 Jul;14(7):1049–1058. doi: 10.1016/0006-2952(65)90033-x. [DOI] [PubMed] [Google Scholar]
  6. Mao J. C. The stoichiometry of erythromycin binding to ribosomal particles of Staphylococcus aureus. Biochem Pharmacol. 1967 Dec;16(12):2441–2443. doi: 10.1016/0006-2952(67)90232-8. [DOI] [PubMed] [Google Scholar]
  7. POLLOCK M. R. Drug resistance and mechanisms for its development. Br Med Bull. 1960 Jan;16:16–22. doi: 10.1093/oxfordjournals.bmb.a069785. [DOI] [PubMed] [Google Scholar]
  8. TAUBENECK U. Susceptibility of Proteus mirabilis and its stable L-forms to erythromycin and other macrolides. Nature. 1962 Oct 13;196:195–196. doi: 10.1038/196195b0. [DOI] [PubMed] [Google Scholar]
  9. TAUBMAN S. B., SO A. G., YOUNG F. E., DAVIE E. W., CORCORAN J. W. EFFECT OF ERYTHROMYCIN ON PROTEIN BIOSYNTHESIS IN BACILLUS SUBTILIS. Antimicrob Agents Chemother (Bethesda) 1963;161:395–401. [PubMed] [Google Scholar]
  10. Tanaka K., Teraoka H. Binding of erythromycin to Escherichia coli ribosomes. Biochim Biophys Acta. 1966 Jan 18;114(1):204–206. doi: 10.1016/0005-2787(66)90272-3. [DOI] [PubMed] [Google Scholar]
  11. Tanaka K., Teraoka H., Nagira T., Tamaki M. Formation of C14-erythromycin-ribosome complex. J Biochem. 1966 Jun;59(6):632–634. doi: 10.1093/oxfordjournals.jbchem.a128355. [DOI] [PubMed] [Google Scholar]
  12. Taubman S. B., Jones N. R., Young F. E., Corcoran J. W. Sensitivity and resistance to erythromycin in Bacillus subtilis 168: the ribosomal binding of erythromycin and chloramphenicol. Biochim Biophys Acta. 1966 Aug 17;123(2):438–440. doi: 10.1016/0005-2787(66)90301-7. [DOI] [PubMed] [Google Scholar]
  13. WOLFE A. D., HAHN F. E. ERYTHROMYCIN: MODE OF ACTION. Science. 1964 Mar 27;143(3613):1445–1446. doi: 10.1126/science.143.3613.1445. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Bacteriology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES