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Antimicrobial Agents and Chemotherapy, November 2004, p. 4281-4285, Vol. 48, No. 11
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.11.4281-4285.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Heterologous Expression of the Enterococcal vanA Operon in Methicillin-Resistant Staphylococcus aureus

Bruno Périchon and Patrice Courvalin*

Unité des Agents Antibactériens, Institut Pasteur, Paris, France

Received 30 April 2004/ Returned for modification 13 June 2004/ Accepted 22 July 2004

Two methicillin- and vancomycin-resistant Staphylococcus aureus strains, MI-VRSA and PA-VRSA, and Enterococcus faecalis DMC83006B, considered to be the potential donor of glycopeptide resistance to MI-VRSA, were studied. MI-VRSA is highly resistant to both glycopeptides, whereas PA-VRSA displays low-level resistance to vancomycin and reduced susceptibility to teicoplanin. We have analyzed the expression of the vanA operon in the three clinical isolates. Determination of the relative amounts of late peptidoglycan precursors and quantification of the D,D-peptidase activities, in the absence or after induction by glycopeptides, revealed that the resistance genes were expressed at similarly high levels in the three strains. Glycopeptide resistance stability in the three strains was studied by replica plating. Resistance was lost at high frequency, ca. 50%, after overnight growth of PA-VRSA in the absence of antibiotics, whereas it was fully stable in MI-VRSA and E. faecalis DMC83006B. Induction of resistance by vancomycin was significantly delayed in PA-VRSA relative to MI-VRSA. Low-level glycopeptide resistance of S. aureus PA-VRSA is thus likely due to instability of the genetic element, plasmid or transposon, carrying the vanA operon associated with a longer lag phase before growth resumes after induction by vancomycin.


* Corresponding author. Mailing address: Unité des Agents Antibactériens, Institut Pasteur, 25, rue du Docteur Roux, 75724 Paris Cedex 15, France. Phone: (33) (1) 45-68-83-20. Fax: (33) (1) 45-68-83-19. E-mail: pcourval{at}pasteur.fr.


Antimicrobial Agents and Chemotherapy, November 2004, p. 4281-4285, Vol. 48, No. 11
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.11.4281-4285.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.




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