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Journal of Bacteriology, December 1999, p. 7566-7570, Vol. 181, No. 24
0021-9193/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Gradual Alterations in Cell Wall Structure and Metabolism in Vancomycin-Resistant Mutants of Staphylococcus aureus

Krzysztof Sieradzki and Alexander Tomasz*

The Rockefeller University, New York, New York 10021

Received 8 July 1999/Accepted 29 September 1999

In five vancomycin-resistant laboratory step mutants selected from the highly and homogeneously methicillin-resistant Staphylococcus aureus strain COL (MIC of methicillin, 800 µg/ml; MIC of vancomycin, 1.5 µg/ml), the gradually increasing levels of resistance to vancomycin were accompanied by parallel decreases in the levels of methicillin resistance and abnormalities in cell wall metabolism. The latter included a gradual reduction in the proportion of highly cross-linked muropeptide species in peptidoglycan, down-regulation of the production of penicillin-binding protein 2A (PBP2A) and PBP4, and hypersensitivity to beta -lactam antibiotics each with a relatively selective affinity for the various staphylococcal PBPs; the PBP2-specific inhibitor ceftizoxime was particularly effective.

* Corresponding author. Mailing address: The Rockefeller University, 1230 York Ave., New York, NY 10021. Phone: (212) 752-6159. Fax: (212) 327-8688. E-mail: tomasz{at}rockvax.rockefeller.edu.

Journal of Bacteriology, December 1999, p. 7566-7570, Vol. 181, No. 24
0021-9193/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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