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Antimicrobial Agents and Chemotherapy, November 1998, p. 2817-2823, Vol. 42, No. 11
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Effects of Subinhibitory Concentrations of Antibiotics on Alpha-Toxin (hla) Gene Expression of Methicillin-Sensitive and Methicillin-Resistant Staphylococcus aureus Isolates

Knut Ohlsen,1 Wilma Ziebuhr,1 Klaus-Peter Koller,2 Wolfgang Hell,3 Thomas A. Wichelhaus,4 and Jörg Hacker1,*

Institut für Molekulare Infektionsbiologie der Universität Würzburg, D-97070 Würzburg,1 Hoechst Marion Roussel Deutschland GmbH, D-65926 Frankfurt am Main,2 Institut für Medizinische Mikrobiologie, Ruhr-Universität Bochum, D-44780 Bochum,3 and Institut für Medizinische Mikrobiologie, Universitätsklinik Frankfurt am Main, D-60596 Frankfurt am Main,4 Germany

Received 18 March 1998/Returned for modification 14 July 1998/Accepted 18 August 1998

Concentrations of antibiotics below the MIC are able to modulate the expression of virulence-associated genes. In this study, the influence of subinhibitory doses of 31 antibiotics on the expression of the gene encoding the staphylococcal alpha-toxin (hla), a major virulence factor of Staphylococcus aureus, was investigated with a novel gene fusion protocol. The most striking observation was a strong induction of hla expression by subinhibitory concentrations of beta -lactams and an almost complete inhibition of alpha-toxin expression by clindamycin. Whereas glycopeptide antibiotics had no effect, the macrolide erythromycin and several aminoglycosides reduced and fluoroquinolones slightly stimulated hla expression. Furthermore, Northern blot analysis of hla mRNA and Western blot (immunoblot) analysis of culture supernatants of both methicillin-sensitive and methicillin-resistant S. aureus strains revealed that methicillin-induced alpha-toxin expression is a common phenomenon of alpha-toxin-producing strains. Some methicillin-resistant S. aureus isolates produced up to 30-fold more alpha-toxin in the presence of 10 µg of methicillin per ml than in its absence. The results indicate that the novel gene fusion technique is a useful tool for studying the modulation of virulence gene expression by antibiotics. Moreover, the results suggest that the effects of certain antibiotics on virulence properties may be relevant for the management of S. aureus infections.

* Corresponding author. Mailing address: Institut für Molekulare Infektionsbiologie der Universität Würzburg, Röntgenring 11, D-97070 Würzburg, Germany. Phone: 49-931-312575. Fax: 49-931-312578. E-mail: J.Hacker{at}rzbox.uni-wuerzburg.de.

Antimicrobial Agents and Chemotherapy, November 1998, p. 2817-2823, Vol. 42, No. 11
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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