1887

Abstract

Summary

The two components of virginiamycin, M and S, separately exerted a reversible bacteriostatic activity on . Their combination increased by a hundredfold the inhibitory activity of each factor and induced a loss of viability of bacteria. Such an irreversible step was preceded by a reversible phase, which was characterized by a long lag in colony formation.

Very short incubation with single virginiamycin components and their combination suddenly and completely blocked protein synthesis, whereas the rate of incorporation of labelled bases and nucleosides into polynucleotides was not altered appreciably unless protein formation was halted completely.

Nevertheless, some alterations of ribosomal RNA metabolism occurred very early after treatment with virginiamycin. The synthesis of 23S rRNA was specifically inhibited. Moreover, the degree of methylation of the rRNA which was made in the presence of the drug was lower than that of the controls. Also, the rRNA labelled in virginiamycin-treated cells was metabolically unstable. This indicates that formation and stability of rRNA, as well as the balance among rRNA species, depend on virginiamycin-sensitive protein synthesis.

Metabolism of pulse-labelled RNA was also altered in the presence of virginiamycin: its half-life was prolonged about sixfold by single components and eightfold by their combination. This was due to an increased turnover of rRNA and to prevention of messenger RNA decay.

It is concluded that peptide chain formation is the primary target of virginiamycins M and S (hence their synergistic antibiotic activity), that translation—not transcription—is prevented by these inhibitors, and that the alterations of nucleic acid metabolism are due to the halt of protein synthesis.

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1969-08-01
2024-04-25
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References

  1. Borek E. 1963; The methylation of transfer RNA: mechanism and function. Cold Spring Harb. Symp. quant. Biol 28:139
    [Google Scholar]
  2. Bray G. A. 1960; A simple efficient liquid scintillator for counting aqueous solutions in a liquid scintillation counter. Analyt. Biochem 1:279
    [Google Scholar]
  3. Ceriotti G. 1955; Determination of nucleic acids in animal tissues. J. biol. Chem 214:59
    [Google Scholar]
  4. Chabbert Y. A., Acar J. F. 1964; Interactions bactériostatiques et bactéricides chez les anti-biotiques du groupe de la streptogramine. Annls Inst. Pasteur, Paris 107:777
    [Google Scholar]
  5. Cocito C. 1963 Biochemical Properties and Metabolism of Nucleic Acids of Viruses, Cells and Virus-infected Cells Leuven: Fonteyn edition;
    [Google Scholar]
  6. Cocito C. 1969; The action of virginiamycin on nucleic acid and protein synthesis in Bacillus subtilis infected with bacteriophage 2C. J. gen. Microbiol 57:195
    [Google Scholar]
  7. Cocito C., De Somer P. 1961; Chromatographic analysis of nucleic acids from mammalian and bacterial cells and viruses. Proc. int. Biophys. Congr., Stockholm220
    [Google Scholar]
  8. Delpierre G. R., Eastwood F. W., Gream G. E., Kingston D. G. I., Sarin P. S., Todd A., Williams D. H. 1966; The structure of ostreogrycin A. Tetrahedron Lett 4:369
    [Google Scholar]
  9. Dubin D. T., Elkort A. T. 1965; A direct demonstration of the metabolic turnover of chloramphenicol RNA. Biochim. biophys. Acta 103:355
    [Google Scholar]
  10. Eastwood F. W., Snell B. K., Todd A. 1960; Antibiotics of the E129 (Ostreogrycin) complex. I. The structure of E129B. J. chem. Soc2286
    [Google Scholar]
  11. Fan D. P., Higa A., Levinthal C. 1964; Messenger RNA decay and protection. J. molec. Biol 8:210
    [Google Scholar]
  12. Giles K. W., Myers A. 1965; An improved diphenylamine method for the estimation of deoxy-ribonucleic acid. Nature, Lond 206:93
    [Google Scholar]
  13. Gordon J., Boman H. G. 1964; Studies on microbial RNA. II. Transfer of methyl groups from methionine to the RNA of a ribonucleoprotein particle. J. molec. Biol 9:638
    [Google Scholar]
  14. Gordon J., Boman H., Isaksson L. 1964; In vivo inhibition of RNA methylation in the presence of chloramphenicol. J. molec. Biol 9:831
    [Google Scholar]
  15. Gosselinckx I. 1963 Scheikundige studie van het antibioticum staphylomycine Thesis, University of Leuven;
    [Google Scholar]
  16. Jolles G., Terlain B., Thomas J. P. 1965; Metabolic investigations on pristinamycin. Nature, Lond 207:199
    [Google Scholar]
  17. Kurland C. G., Maaløe O. 1962; Regulation of ribosomal and transfer RNA synthesis. J. molec. Biol 4:193
    [Google Scholar]
  18. Lindberg O., Ernster L. 1956; Determination of organic phosphorus compounds by phosphate analysis. Meth. biochem. Analysis 3:1
    [Google Scholar]
  19. Lowry O. H., Rosebrough N. J., Farr A. L., Randall R. J. 1951; Protein measurement with Folin phenol reagent. J. biol. Chem 193:265
    [Google Scholar]
  20. Murat M., Pellerat J. 1965; Etude comparative des pouvoirs bactériostatiques et bactéricides de la pristinamycine, de la méthicilline et de la pérucilline sur un certain nombre de souches de staphylocoques et de streptocoques hémolytiques. Annls Inst. Pasteur, Paris 109:317
    [Google Scholar]
  21. Nakada D. 1965; Ribosome formation by puromycin-treated B. subtilis. Biochim. biophys. Acta 103:455
    [Google Scholar]
  22. Nakada D., Anderson I. A. C., Magasanik B. 1964; Fate of the ribosomal RNA produced by a ‘relaxed’ mutant of E. coli. J. molec. Biol 9:472
    [Google Scholar]
  23. Neidhardt F., Gros F. 1957; Metabolic instability of the ribonucleic acid synthesized by E. coli in the presence of chloromycetin. Biochim. biophys. Acta 25:513
    [Google Scholar]
  24. Otaka E., Osawa S., Sibatani A. 1964; Stimulation of 14C-leucine incorporation into protein in vitro by ribosomal RNA of E. coli. Biochem. biophys. Res. Commun 15:568
    [Google Scholar]
  25. Schaechter M. 1963; Bacterial polyribosomes and their participation in protein synthesis in vivo. J. molec. Biol 7:561
    [Google Scholar]
  26. Spizizen J. 1958; Transformation of biochemically deficient strains of B. subtilis by deoxyribonucleate. Proc. natn. Acad. SciU.S.A 441072
    [Google Scholar]
  27. Vanderhaeghe G., Parmentier G. 1960; The structure of factor S of staphylomycin. J. Am. chem. Soc 82:4414
    [Google Scholar]
  28. Vanderhaeghe H., van Duck P., Parmentier G., De Somer P. 1957; Isolation and properties of the components of staphylomycin. Antibiotics Chemother 3:606
    [Google Scholar]
  29. Vazquez D. 1966a; Mode of action of chloramphenicol and related antibiotics. Symp. Soc. gen Microbiol 16:169
    [Google Scholar]
  30. Vazquez D. 1966b; Studies on the mode of action of the streptogramin antibiotics. J. gen. Microbiol 42:93
    [Google Scholar]
  31. Vazquez D. 1966c; Antibiotics affecting chloramphenicol uptake by bacteria. Their effect on amino acid incorporation in a cell-free system. Biochim. biophys. Acta 114:289
    [Google Scholar]
  32. Vazquez D. 1966d; Binding of chloramphenicol to ribosomes. The effect of a number of antibiotics. Biochim. biophys. Acta 114:277
    [Google Scholar]
  33. Videau D. 1965; La pristinamycine et le phénomène de bactériopause. Annls Inst. Pasteur, Paris 108:602
    [Google Scholar]
  34. Yamaguchi H., Tanaka N. 1964; Selective toxicity of mikamycins, inhibitors of protein synthesis. Nature, Lond 201:499
    [Google Scholar]
  35. Young F. E., Spizizen J. 1963; Incorporation of DNA in the B. subtilis transformation system. J. Bact 86:392
    [Google Scholar]
  36. Yudkin M. D., Davis B. 1965; Nature of the RNA associated with the protoplast membrane of B. megaterium. J. molec. Biol 12:193
    [Google Scholar]
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