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 virginia-mycins 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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