The post antibiotic effect of streptogramins on gram-positive bacteria primarily arises from the type a component

The post-antibiotic effect (PAE) is the delay in bacterial regrowth following removal of an antibiotic and has important implications for dosing regimens. Several classes of antibiotics generate PAEs including the streptogramins which are comprised of two components, type A and type B, that bind to adjacent sites on the ribosome and act synergistically to inhibit bacterial growth. In the present work, we investigated the activity of the type A and type B streptogramins virginiamycin (VM1) and virginiamycin (VS1) toward two Gram-positive bacteria, Bacillus subtilis and Staphylococcus aureus. In agreement with previous studies, we show that the combination of VM1 and VS1 resulted in synergistic antibacterial activity defined by the minimum inhibitor concentration (MIC). However, the PAE generated by VM1 was similar to that of the VM1 VS1 combination, whereas VS1 generated only a minimal PAE. These data contrast with the general expectation that the synergy resulting from the combination of streptogramins lowers both the MIC and extends the PAE compared to either component alone, and again reflecting fundamental differences in drug activity at fixed concentrations compared to time-dependent activity.