Subinhibitory quinupristin/dalfopristin attenuates virulence of Staphylococcus aureus

1 Institute for Medical Microbiology, Immunology and Hygiene, Medical Center, University of Cologne, Goldenfelsstrasse 19-21 50935 Köln, Germany
Received 19 September 2005; returned 10 March 2006; revised 5 May 2006; accepted 23 June 2006
*Corresponding author. Tel: +49-221-478 3018; Fax: +49-221-478-3067; E-mail: Oleg.Krut{at}uni-koeln.de
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 Gram-positive cocci.
Methods: The activity of quinupristin/dalfopristin on exotoxin release by S. aureus was investigated by 2D SDSPAGE 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,
- and ß-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.
Keywords: proteomics , exoproteins , mass spectrometry , antibiotics
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