Vancomycin-Dependent Enterococcus faecalis Clinical Isolates and Revertant Mutants
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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 vanS B - vanR B 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 VanS B 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 VanS B , 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.
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The vancomycin-dependent phenotype seems unstable because mutations in the VanS sensor or promoter regions frequently revert the phenotype.
“This phenotype seems to be unstable since mutations in the VanS sensor or promoter regions frequently revert the phenotype (81).”
From Mechanisms of Antibiotic Resistance (2016) · cites this paper as [81]
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- Authors
- Van Bambeke, F., Chauvel, M., Reynolds, P. E., Fraimow, H. S., & Courvalin, P.
- Affiliations
- <!--label omitted: 1-->Unité des Agents Antibactériens, Institut Pasteur, 75724 Paris Cedex 15, France1;
- Institut Pasteur (FR)
- University of Cambridge (GB)
- Graduate Hospital (US)
- ORCID
- Fraimow, Henry S.
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 1999-01
- Volume
- 43
- Issue
- 1
- Pages
- 41-47
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC89018
- OpenAlex
- W2105673202
- Cited by
- 88
- References
- 31
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 1 · 2020: 2 · 2019: 3 · 2018: 2 · 2017: 2 · 2016: 5 · 2015: 2 · 2014: 4 · 2013: 1 · 2012: 3
- FWCI
- 3.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DIAL (Catholic University of Leuven) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
- Keywords
- Enterococcus faecalis, vancomycin resistance, peptidoglycan precursor, two-component systems, teicoplanin resistance, autophosphorylation sites, clinical isolates
- MeSH terms
- Anti-Bacterial Agents, Bacterial Proteins, Cloning, Molecular, Drug Resistance, Microbial, Electrophoresis, Polyacrylamide Gel, Genotype, Mutation, Peptide Synthases, Phenotype, Enterococcus faecalis, Vancomycin, Teicoplanin
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