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Infection and Immunity, May 2001, p. 2996-3003, Vol. 69, No. 5
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.5.2996-3003.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Subinhibitory Clindamycin Differentially Inhibits Transcription of Exoprotein Genes in Staphylococcus aureus

Silvia Herbert, Peter Barry, and Richard P. Novick*

Program in Molecular Pathogenesis, Skirball Institute, and Department of Microbiology, New York University School of Medicine, New York, New York 10016

Received 14 August 2000/Returned for modification 4 October 2000/Accepted 29 January 2001

It has long been known that certain antibiotics, at subinhibitory concentrations, differentially inhibit the synthesis of alpha -hemolysin and other staphylococcal virulence factors. In this report, we show that subinhibitory clindamycin (SBCL) eliminates production of nearly all exoproteins by Staphylococcus aureus but has virtually no effect on cytoplasmic proteins. The effect was abolished by a gene conferring resistance to macrolides-lincosamides-streptogramin B, showing that differential inhibition of protein synthesis is responsible; remarkably, however, subinhibitory clindamycin blocked production of several of the individual exoprotein genes, including spa (encoding protein A), hla (encoding alpha -hemolysin), and spr (encoding serine protease), at the level of transcription, suggesting that the primary effect must be differential inhibition of the synthesis of one or more regulatory proteins. In contrast to earlier reports, however, we found that subinhibitory clindamycin stimulates synthesis of coagulase and fibronectin binding protein B, also at the level of transcription. agr and sar expression was minimally affected by subinhibitory clindamycin. These effects varied from strain to strain and do not seem to be responsible for the effects of subinhibitory clindamycin on the overall exoprotein pattern.

* Corresponding author. Mailing address: Program in Molecular Pathogenesis, Skirball Institute, and Department of Microbiology, New York University School of Medicine, 540 First Ave., New York, NY 10016. Phone: (212) 263-6290. Fax: (212) 263-5711. E-mail: RICHARD.NOVICK{at}MCSKA.MED.NYU.EDU.

Infection and Immunity, May 2001, p. 2996-3003, Vol. 69, No. 5
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.5.2996-3003.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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