This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Van Bambeke, F.
Right arrow Articles by Courvalin, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Van Bambeke, F.
Right arrow Articles by Courvalin, P.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, January 1999, p. 41-47, Vol. 43, No. 1
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Vancomycin-Dependent Enterococcus faecalis Clinical Isolates and Revertant Mutants

Françoise Van Bambeke,1,dagger Murielle Chauvel,1 Peter E. Reynolds,2 Henry S. Fraimow,3 and Patrice Courvalin1,*

Unité des Agents Antibactériens, Institut Pasteur, 75724 Paris Cedex 15, France1; Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, United Kingdom2; and Department of Medicine, The Graduate Hospital, Philadelphia, Pennsylvania3

Received 24 June 1998/Returned for modification 25 August 1998/Accepted 13 October 1998

Three vancomycin-dependent clinical isolates of Enterococcus faecalis of the VanB type were studied by determining (i) the sequence of the ddl gene encoding the host D-Ala:D-Ala ligase and the vanSB-vanRB genes specifying the two-component regulatory system that activates transcription of the vanB operon, (ii) the level of expression of resistance genes by using DD-dipeptidase activity as a reporter, and (iii) the proportions of the peptidoglycan precursors synthesized. Each strain had a mutation in ddl leading to an amino acid substitution (D295 to V; T316 to I) or deletion (DAK251-253 to E) at invariant positions in D-Ala:D-Ala, D-Ala:D-Lac, and D-Ala:D-Ser ligases. These mutations resulted in impaired host D-Ala:D-Ala ligases since only precursors terminating in D-Ala-D-Lac were synthesized under vancomycin-inducing conditions. Two types of vancomycin-independent revertants of one isolate were obtained in vitro after growth in the absence of vancomycin: (i) vancomycin-resistant, teicoplanin-susceptible mutants had a 6-bp insertion in the host ddl gene, causing the E251-to-EYK change that restored D-Ala:D-Ala ligase activity, (ii) constitutive vancomycin-resistant, teicoplanin-resistant mutants had substitutions (S232 to F or E247 to K) in the vicinity of the autophosphorylation site of the VanSB sensor and produced exclusively precursors ending in D-Ala-D-Lac. Vancomycin- and teicoplanin-dependent mutants obtained by growth in the presence of teicoplanin had an 18-bp deletion in VanSB, affecting residues 402 to 407 and overlapping the G2 ATP binding domain. The rapid emergence of vancomycin-independent revertants in vitro suggests that interruption of vancomycin therapy may not be sufficient to cure patients infected with vancomycin-dependent enterococci.

* Corresponding author. Mailing address: Unité des Agents Antibactériens, Institut Pasteur, 25, rue du Dr 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.

dagger Present address: Unité de Pharmacologie Cellulaire et Moléculaire, Université Catholique de Louvain, 1200 Brussels, Belgium.

Antimicrobial Agents and Chemotherapy, January 1999, p. 41-47, Vol. 43, No. 1
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Perichon, B., Courvalin, P. (2009). VanA-Type Vancomycin-Resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 53: 4580-4587 [Abstract] [Full Text]  
  • Moubareck, C., Meziane-Cherif, D., Courvalin, P., Perichon, B. (2009). VanA-Type Staphylococcus aureus Strain VRSA-7 Is Partially Dependent on Vancomycin for Growth. Antimicrob. Agents Chemother. 53: 3657-3663 [Abstract] [Full Text]  
  • San Millan, A., Depardieu, F., Godreuil, S., Courvalin, P. (2009). VanB-Type Enterococcus faecium Clinical Isolate Successively Inducibly Resistant to, Dependent on, and Constitutively Resistant to Vancomycin. Antimicrob. Agents Chemother. 53: 1974-1982 [Abstract] [Full Text]  
  • Hawley, J. S., Murray, C. K., Jorgensen, J. H. (2007). Development of Colistin-Dependent Acinetobacter baumannii-Acinetobacter calcoaceticus Complex. Antimicrob. Agents Chemother. 51: 4529-4530 [Full Text]  
  • Goldstein, F., Perutka, J., Cuirolo, A., Plata, K., Faccone, D., Morris, J., Sournia, A., Kitzis, M. D., Ly, A., Archer, G., Rosato, A. E. (2007). Identification and Phenotypic Characterization of a {beta}-Lactam-Dependent, Methicillin-Resistant Staphylococcus aureus Strain. Antimicrob. Agents Chemother. 51: 2514-2522 [Abstract] [Full Text]  
  • Depardieu, F., Kolbert, M., Pruul, H., Bell, J., Courvalin, P. (2004). VanD-Type Vancomycin-Resistant Enterococcus faecium and Enterococcus faecalis. Antimicrob. Agents Chemother. 48: 3892-3904 [Abstract] [Full Text]  
  • Depardieu, F., Reynolds, P. E., Courvalin, P. (2003). VanD-Type Vancomycin-Resistant Enterococcus faecium 10/96A. Antimicrob. Agents Chemother. 47: 7-18 [Abstract] [Full Text]  
  • Ambur, O.-H., Reynolds, P. E., Arias, C. A. (2002). D-Ala:D-Ala Ligase Gene Flanking the vanC Cluster: Evidence for Presence of Three Ligase Genes in Vancomycin-Resistant Enterococcus gallinarum BM4174. Antimicrob. Agents Chemother. 46: 95-100 [Abstract] [Full Text]  
  • Arthur, M., Quintiliani, R. Jr. (2001). Regulation of VanA- and VanB-Type Glycopeptide Resistance in Enterococci. Antimicrob. Agents Chemother. 45: 375-381 [Full Text]  
  • Arias, C. A., Courvalin, P., Reynolds, P. E. (2000). vanC Cluster of Vancomycin-Resistant Enterococcus gallinarum BM4174. Antimicrob. Agents Chemother. 44: 1660-1666 [Abstract] [Full Text]  
  • Boyd, D. A., Conly, J., Dedier, H., Peters, G., Robertson, L., Slater, E., Mulvey, M. R. (2000). Molecular Characterization of the vanD Gene Cluster and a Novel Insertion Element in a Vancomycin-Resistant Enterococcus Isolated in Canada. J. Clin. Microbiol. 38: 2392-2394 [Abstract] [Full Text]  
  • Arthur, M., Depardieu, F., Reynolds, P., Courvalin, P. (1999). Moderate-Level Resistance to Glycopeptide LY333328 Mediated by Genes of the vanA and vanB Clusters in Enterococci. Antimicrob. Agents Chemother. 43: 1875-1880 [Abstract] [Full Text]  
  • Casadewall, B., Courvalin, P. (1999). Characterization of the vanD Glycopeptide Resistance Gene Cluster from Enterococcus faecium BM4339. J. Bacteriol. 181: 3644-3648 [Abstract] [Full Text]  
  • Lefort, A., Baptista, M., Fantin, B., Depardieu, F., Arthur, M., Carbon, C., Courvalin, P. (1999). Two-Step Acquisition of Resistance to the Teicoplanin-Gentamicin Combination by VanB-Type Enterococcus faecalis In Vitro and in Experimental Endocarditis. Antimicrob. Agents Chemother. 43: 476-482 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»