Resistance in Staphylococcus aureus: Induction of Macrolide-Resistant Protein Synthesis

Induction of resistance to macrolide-, lincosamide-, and streptogramin B-type antibiotics in Staphylococcus aureus was studied by monitoring the appearance of erythromycin A (EM)-resistant [14C]leucine incorporation. Examination of the induction process revealed saturation kinetics and a time course much like that reported for penicillinase in gram-positive bacteria. Induction kinetics in exponentially growing cells were sigmoidal and appeared to reach a maximum and constant rate when growth reached stationary phase. Since the induction of EM-resistant colony-forming ability was complete within 60 min, ribosome modification cannot be limited to a fraction of the population and must occur in essentially every cell. However, EM-resistant growth was expressed in cells where less than half the ['4C]leucine-incorporating activity was resistant to EM. This suggests that resistance requires that only a threshold level of ribosome modification be exceeded and that, once exceeded, resistance is dominant to sensitivity.