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Antimicrobial Agents and Chemotherapy, December 2004, p. 4566-4573, Vol. 48, No. 12
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.12.4566-4573.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Penicillin-Binding Protein 2 Is Essential for Expression of High-Level Vancomycin Resistance and Cell Wall Synthesis in Vancomycin- Resistant Staphylococcus aureus Carrying the Enterococcal vanA Gene Complex

Anatoly Severin,1,{dagger} Shang Wei Wu,1 Keiko Tabei,2 and Alexander Tomasz1*

The Rockefeller University, New York,1 Wyeth, Pearl River, New York2

Received 13 February 2004/ Returned for modification 19 April 2004/ Accepted 26 June 2004

A combination of biochemical and genetic experiments were performed in order to better understand the mechanism of expression of high-level vancomycin resistance in Staphylococcus aureus. The transcription of pbp2 of the highly vancomycin- and oxacillin-resistant strain COLVA200 and its mutant derivative with inactivated mecA were put under the control of an inducible promoter, and the dependence of oxacillin and vancomycin resistance and cell wall composition on the concentration of the isopropyl-ß-D-thiogalactopyranoside inducer was determined. The results indicate that mecA—the genetic determinant of oxacillin resistance—while essential for oxacillin resistance, is not involved with the expression of vancomycin resistance. Penicillin binding protein 2A, the protein product of mecA, appears to be unable to utilize the depsipeptide cell wall precursor produced in the vancomycin-resistant cells for transpeptidation. The key penicillin binding protein essential for vancomycin resistance and for the synthesis of the abnormally structured cell walls characteristic of vancomycin-resistant S. aureus (A. Severin, K. Tabei, F. Tenover, M. Chung, N. Clarke, and A. Tomasz, J. Biol. Chem. 279:3398-3407, 2004) is penicillin binding protein 2.

* Corresponding author. Mailing address: The Rockefeller University, Box 152, 1230 York Ave., New York, NY 10021. Phone: (212) 327-8277. Fax: (212) 327-8688. E-mail: tomasz{at}mail.rockefeller.edu.

{dagger} Present address: Wyeth, Pearl River, NY 10965.

Antimicrobial Agents and Chemotherapy, December 2004, p. 4566-4573, Vol. 48, No. 12
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.12.4566-4573.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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