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Updated: Jun 25, 2026
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Nanomechanics of Drug-target Interactions and Antibacterial Resistance Detection
Published on: October 25, 2013
New combinations of mutations in VanD-Type vancomycin-resistant Enterococcus faecium, Enterococcus faecalis, and
F Depardieu1, M-L Foucault, J Bell
1Unité des Agents Antibactériens, Institut Pasteur, 25, rue du Docteur Roux, 75724 Paris Cedex 15, France.
Antimicrobial Agents and Chemotherapy
|March 5, 2009
Summary
This study investigated vancomycin-resistant Enterococcus strains, identifying mutations in VanS(D) and Ddl ligase that cause constitutive resistance. These findings highlight that while VanD-type resistance often involves sensor mutations, the Ddl ligase is not always impaired.
Area of Science:
- Microbiology
- Genetics
- Molecular Biology
Background:
- Vancomycin resistance in Enterococcus is a significant clinical concern.
- The VanD type resistance mechanism involves specific genetic elements and pathways.
- Understanding the genetic basis of resistance is crucial for developing new therapeutic strategies.
Purpose of the Study:
- To characterize the genetic mutations responsible for vancomycin and teicoplanin resistance in five clinical Enterococcus isolates.
- To investigate the role of the vanD gene cluster and its associated genes in conferring constitutive resistance.
- To determine the impact of these mutations on the Ddl D-Ala:D-Ala ligase and D,D-carboxypeptidase activities.
Main Methods:
- Phenotypic characterization of vancomycin and teicoplanin resistance levels (MICs).
- Genetic analysis of the vanD gene cluster, including sequencing of vanS(D) and Ddl genes.
- Investigation of insertion sequences and their impact on gene function (e.g., vanY(D)).
Main Results:
- Five distinct clinical isolates of Enterococcus (E. faecium, E. avium, E. faecalis) exhibited varying levels of vancomycin and teicoplanin resistance.
- All strains possessed a chromosomal vanD gene cluster and constitutively synthesized peptidoglycan precursors ending in D-alanyl-D-lactate.
- Mutations were identified in conserved domains of VanS(D), leading to constitutive activation, and in the Ddl ligase, often impairing its function, though one strain showed a functional Ddl enzyme.
- An insertion sequence (ISEfa9) in vanY(D) of one strain resulted in absent D,D-carboxypeptidase activity.
- The vanD gene clusters were assigned to two subtypes: vanD-1 and vanD-4.
Conclusions:
- Mutations in vanS(D) or vanR(D) are essential for constitutive resistance in VanD-type strains.
- The Ddl host ligase is not consistently impaired in VanD-type resistant strains.
- The study provides insights into the diverse mutational landscape driving vancomycin resistance in Enterococcus.
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