Binding parameters and microbiological activity of macrolides, lincosamides and streptogramins against Staphylococcus aureus.
Parameters of erythromycin binding to Staphylococcus aureus were measured in-vitro using an equilibrium method with [3H]erythromycin. The dissociation constant of the complex, erythromycin-S. aureus sensitive strain, was KD = 0.11 microM. The maximal binding, representing the density of binding sites was 14,847 molecules/cell. No binding was detectable on the constitutive resistant strain. Macrolides, streptogramins and lincosamides displaced bound [3H]erythromycin by a competitive process indicating that these compounds share common binding sites on the bacteria, i.e. 50 S ribosomal subunits. A good correlation (r = 0.99) was demonstrated between the corresponding inhibition constants (Ki) and the minimal inhibitory concentration. It is proposed that knowledge of the binding parameters provides a good indication of bacterial susceptibility and may serve as a useful adjunct in developing new compounds.
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004917:Erythromycin / Q000378:metabolism*; D055231:Lincosamides; D018942:Macrolides; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism; D014316:Tritium; D014769:Virginiamycin / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D055231:Lincosamides; D018942:Macrolides; D014316:Tritium; D014769:Virginiamycin; D004917:Erythromycin