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Journal of Antimicrobial Chemotherapy 2006 58(3):564-574; doi:10.1093/jac/dkl291
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© The Author 2006. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

Subinhibitory quinupristin/dalfopristin attenuates virulence of Staphylococcus aureus

Carmen Koszczol, Katussevani Bernardo{dagger}, Martin Krönke and Oleg Krut*

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 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, {alpha}- 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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