Subinhibitory quinupristin/dalfopristin attenuates virulence of Staphylococcus aureus

Objectives: The semi-synthetic streptogramin quinupristin/dalfopristin antibiotic exerts potent bactericidal activity against Staphylococcus aureus. We investigated whether, like other bactericidal antibiotics used at subinhibitory concentrations, quinupristin/dalfopristin enhances release of toxins by Grampositive cocci. Methods: The activity of quinupristin/dalfopristin on exotoxin release by S. aureus was investigated by 2D SDS–PAGE combined with MALDI-TOF/MS analysis and by western blotting. Results: We show that quinupristin/dalfopristin at subinhibitory concentrations reduces the release of S. aureus factors that induce tumour necrosis factor secretion in macrophages. Furthermore, quinupristin/dalfopristin but not linezolid attenuated S. aureus-mediated killing of infected host cells. When added to S. aureus cultures at different stages of bacterial growth, quinupristin/dalfopristin reduced in a dose-dependent manner the release of specific virulence factors (e.g. autolysin, protein A, aand b-haemolysins, lipases). In contrast, other presumably non-toxic exoproteins remained unchanged. Conclusions: The results of the present study suggest that subinhibitory quinupristin/dalfopristin inhibits virulence factor release by S. aureus, which might be especially helpful for the treatment of S. aureus infections, where both bactericidal as well as anti-toxin activity may be advantageous.