ArticleThe Journal of antimicrobial chemotherapy2021
Alternative vanHAX promoters and increased vanA-plasmid copy number resurrect silenced glycopeptide resistance in Enterococcus faecium.
Article in The Journal of antimicrobial chemotherapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- Pangenomics insights of enterococcus faecium human isolates and identification of novel therapeutic targets by in silico subtractive genomics.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2026Article
- Heteroresistance in vancomycin-variable Enterococcus faecium ST80 isolate.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026Article
- Resistome Profiling of a Large Collection ofInternational journal of molecular sciences · 2026Article
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- Vancomycin-variable enterococci as a silent reservoir of resistance: characterization of the first reported vancomycin-variableFrontiers in microbiology · 2026Article
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- Development of a strain-specific PCR as a diagnostic tool for surveillance, detection, and monitoring of vancomycin-resistant Enterococcus faecium during outbreak.Antimicrobial resistance and infection control · 2025Article
- Prevalence and Molecular Characterization of Vancomycin VariableAnnals of laboratory medicine · 2024Article
- Genetic analysis of vancomycin-variable Enterococcus faecium clinical isolates in Italy.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2024Article
- Integration of vanHAX downstream of a ribosomal RNA operon restores vancomycin resistance in a susceptible Enterococcus faecium strain.npj antimicrobials and resistance · 2024Article
- "Keeping us on our toes": a review of what clinicians need to know about vancomycin-variableAntimicrobial stewardship & healthcare epidemiology : ASHE · 2024Review
- The population structure of vancomycin-resistant and -susceptibleMicrobial genomics · 2023Article
- Transiently silent acquired antimicrobial resistance: an emerging challenge in susceptibility testing.The Journal of antimicrobial chemotherapy · 2023Review
- Occult Vancomycin-ResistantAntibiotics (Basel, Switzerland) · 2023Article
- Vancomycin-variable enterococci in sheep and cattle isolates and whole-genome sequencing analysis of isolates harboringIranian journal of veterinary research · 2023Article
- A Simple and Rapid Low-Cost Procedure for Detection of Vancomycin-Resistance Genes in Enterococci Reveals an Outbreak of Vancomycin-VariableDiagnostics (Basel, Switzerland) · 2022Article
- Pharmacokinetics and pharmacodynamics of peptide antibiotics.Advanced drug delivery reviews · 2022Review
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundVancomycin variable enterococci (VVE) are van-positive isolates with a susceptible phenotype that can convert to a resistant phenotype during vancomycin selection.
objectivesTo describe a vancomycin-susceptible vanA-PCR positive ST203 VVE Enterococcus faecium isolate (VVESwe-S) from a liver transplantation patient in Sweden which reverted to resistant (VVESwe-R) during in vitro vancomycin exposure.
methodsWGS analysis revealed the genetic differences between the isolates. Expression of the van-operon was investigated by qPCR. Fitness and stability of the revertant were investigated by growth measurements, competition and serial transfer.
resultsThe VVESwe-R isolate gained high-level vancomycin (MIC >256 mg/L) and teicoplanin resistance (MIC = 8 mg/L). VVESwe-S has a 5'-truncated vanR activator sequence and the VVESwe-R has in addition acquired a 44 bp deletion upstream of vanHAX in a region containing alternative putative constitutive promoters. In VVESwe-R the vanHAX-operon is constitutively expressed at a level comparable to the non-induced prototype E. faecium BM4147 strain. The vanHAX operon of VVESwe is located on an Inc18-like plasmid, which has a 3-4-fold higher copy number in VVESwe-R compared with VVESwe-S. Resistance has a low fitness cost and the vancomycin MIC of VVESwe-R decreased during in vitro serial culture without selection. The reduction in MIC was associated with a decreased vanA-plasmid copy number.
conclusionsOur data support a mechanism by which vancomycin-susceptible VVE strains may revert to a resistant phenotype through the use of an alternative, constitutive, vanR-activator-independent promoter and a vanA-plasmid copy number increase.
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