Molecular investigation of the postantibiotic effects of clarithromycin and erythromycin on Staphylococcus aureus cells.

The kinetics of recovery after inhibition of growth by erythromycin and clarithromycin were examined in Staphylococcus aureus cells. After inhibition for one mass doubling by 0.5 microg of the antibiotics/ml, a postantibiotic effect (PAE) of 3 and 4 h duration was observed for the two drugs before growth resumed. Cell viability was reduced by 25% with erythromycin and 45% with clarithromycin compared with control cells. Erythromycin and clarithromycin treatment reduced the number of 50S ribosomal subunits to 24 and 13% of the number found in untreated cells. 30S subunit formation was not affected. Ninety minutes was required for resynthesis to give the control level of 50S particles. Protein synthesis rates were diminished for up to 4 h after the removal of the macrolides. This continuing inhibition of translation was the result of prolonged binding of the antibiotics to the 50S subunit as measured by 14C-erythromycin binding to ribosomes in treated cells. The limiting factors in recovery from macrolide inhibition in these cells, reflected as a PAE, are the time required for the synthesis of new 50S subunits and the slow loss of the antibiotics from ribosomes in inhibited cells.