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Journal of Bacteriology, December 2003, p. 7103-7110, Vol. 185, No. 24
0021-9193/03/$08.00+0     DOI: 10.1128/JB.185.24.7103-7110.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Alterations of Cell Wall Structure and Metabolism Accompany Reduced Susceptibility to Vancomycin in an Isogenic Series of Clinical Isolates of Staphylococcus aureus

K. Sieradzki and A. Tomasz*

The Rockefeller University, New York, New York 10021

Received 2 June 2003/ Accepted 17 September 2003

A series of isogenic methicillin-resistant Staphylococcus aureus isolates recovered from a bacteremic patient were shown to acquire gradually increasing levels of resistance to vancomycin during chemotherapy with the drug (K. Sieradzki, T. Leski, L. Borio, J. Dick, and A. Tomasz, J. Clin. Microbiol. 41:1687-1693, 2003). We compared properties of the earliest (parental) vancomycin-susceptible isolate, JH1 (MIC, 1 µg/ml), to two late (progeny) isolates, JH9 and JH14 (vancomycin MIC, 8 µg/ml). The resistant isolates produced abnormally thick cell walls and poorly separated cells when grown in antibiotic-free medium. Chemical analysis of the resistant isolates showed decreased cross-linkage of the peptidoglycan and drastically reduced levels of PBP4 as determined by the fluorographic assay. Resistant isolates showed reduced rates of cell wall turnover and autolysis. In vitro hydrolysis of resistant cell walls by autolytic extracts prepared from either susceptible or resistant strains was also slow, and this abnormality could be traced to a quantitative (or qualitative) change in the wall teichoic acid component of resistant isolates. Some change in the structure and/or metabolism of teichoic acids appears to be an important component of the mechanism of decreased susceptibility to vancomycin in S. aureus.

* Corresponding author. Mailing address: The Rockefeller University, 1230 York Ave., New York, NY 10021. Phone: (212) 327 8277. Fax: (212) 327 8688. E-mail: tomasz{at}mail.rockefeller.edu.

Journal of Bacteriology, December 2003, p. 7103-7110, Vol. 185, No. 24
0021-9193/03/$08.00+0     DOI: 10.1128/JB.185.24.7103-7110.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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