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Antimicrobial Agents and Chemotherapy, May 2009, p. 1974-1982, Vol. 53, No. 5
0066-4804/09/$08.00+0     doi:10.1128/AAC.00034-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

VanB-Type Enterococcus faecium Clinical Isolate Successively Inducibly Resistant to, Dependent on, and Constitutively Resistant to Vancomycin{triangledown}

Alvaro San Millan,1,§,{ddagger} Florence Depardieu,1,§ Sylvain Godreuil,2 and Patrice Courvalin1*

Institut Pasteur, Unité des Agents Antibactériens, 75724 Paris Cedex 15, France,1 Laboratoire de Bactériologie, Hôpital Universitaire Arnaud de Villeneuve, F-34295 Montpellier Cedex 5, France2

Received 9 January 2009/ Returned for modification 14 February 2009/ Accepted 28 February 2009

Three Enterococcus faecium strains isolated successively from the same patient, vancomycin-resistant strain BM4659, vancomycin-dependent strain BM4660, and vancomycin-revertant strain BM4661, were indistinguishable by pulsed-field gel electrophoresis and harbored plasmid pIP846, which confers VanB-type resistance. The vancomycin dependence of strain BM4660 was due to mutation P175L, which suppressed the activity of the host Ddl D-Ala:D-Ala ligase. Reversion to resistance in strain BM4661 was due to a G-to-C transversion in the transcription terminator of the vanRSB operon that lowered the free energy of pairing from –13.08 to –6.65 kcal/mol, leading to low-level constitutive expression of the resistance genes from the PRB promoter, as indicated by analysis of peptidoglycan precursors and of VanXB D,D-dipeptidase activity. Transcription of the resistance genes, studied by Northern hybridization and reverse transcription, initiated from the PYB resistance promoter, was inducible in strains BM4659 and BM4660, whereas it started from the PRB regulatory promoter in strain BM4661, where it was superinducible. Strain BM4661 provides the first example of reversion to vancomycin resistance of a VanB-type dependent strain not due to a compensatory mutation in the ddl or vanSB gene. Instead, a mutation in the transcription terminator of the regulatory genes resulted in transcriptional readthrough of the resistance genes from the PRB promoter in the absence of 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

{triangledown} Published ahead of print on 9 March 2009.

§ These authors contributed equally to this work.

{ddagger} Present address: Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense de Madrid, 28040 Madrid, Spain.

Antimicrobial Agents and Chemotherapy, May 2009, p. 1974-1982, Vol. 53, No. 5
0066-4804/09/$08.00+0     doi:10.1128/AAC.00034-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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