ArticleAntimicrobial agents and chemotherapy2016
A Silenced vanA Gene Cluster on a Transferable Plasmid Caused an Outbreak of Vancomycin-Variable Enterococci.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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44 citing papers in PubMed, 69 citations in OpenAlex.
- Evaluation of resistance mechanisms and susceptibility testing in Enterococcus spp.: implications of vancomycin-variable isolates and optrA-mediated resistance.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026Article
- Article
- When Culture Results Don't Tell the Whole Story: A Practical Review of Antibiotics Pitfalls for Clinical Decision-Making.Infectious diseases and therapy · 2026Review
- 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
- Global dissemination of optrA-mediated linezolid resistance in enterococci.The Journal of antimicrobial chemotherapy · 2026Article
- Vancomycin variable Enterococci in the Netherlands (2018-2023) and the mechanism of resistance induction.PloS one · 2026Article
- Vancomycin-variable enterococci as a silent reservoir of resistance: characterization of the first reported vancomycin-variableFrontiers in microbiology · 2026Article
- Surveillance and Characterization of Vancomycin-Resistant and Vancomycin-Variable Enterococci in a Hospital Setting.Antibiotics (Basel, Switzerland) · 2025Article
- 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
- The healthy human gut can take it all: vancomycin-variable, linezolid-resistant strains and specific bacteriocin-species interplay inApplied and environmental microbiology · 2025Article
- Detection of vanA genes in vancomycin-susceptible Enterococcus faecium isolates: implications for additional testing.Access microbiology · 2025Article
- Prevalence of Vancomycin-Variable Enterococci from the Bloodstream in the Korea Global Antibiotic Resistance Surveillance System, 2017-2022.Antibiotics (Basel, Switzerland) · 2024Article
- Reduced vancomycin susceptibility in Staphylococcus aureus clinical isolates: a spectrum of less investigated uncertainties.BMC infectious diseases · 2024Article
- Prevalence and Molecular Characterization of Vancomycin VariableAnnals of laboratory medicine · 2024Article
- CRISPR-Cas System, Antimicrobial Resistance, andBiomedicines · 2024Article
- Surveillance of vancomycin-resistant enterococci reveals shift in dominating clusters fromEuro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin · 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
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We report an outbreak of vancomycin-variable vanA(+) enterococci (VVE) able to escape phenotypic detection by current guidelines and demonstrate the molecular mechanisms for in vivo switching into vancomycin resistance and horizontal spread of the vanA cluster. Forty-eight vanA(+) Enterococcus faecium isolates and one Enterococcus faecalis isolate were analyzed for clonality with pulsed-field gel electrophoresis (PFGE), and their vanA gene cluster compositions were assessed by PCR and whole-genome sequencing of six isolates. The susceptible VVE strains were cultivated in brain heart infusion broth containing vancomycin at 8 μg/ml for in vitro development of resistant VVE. The transcription profiles of susceptible VVE and their resistant revertants were assessed using quantitative reverse transcription-PCR. Plasmid content was analyzed with S1 nuclease PFGE and hybridizations. Conjugative transfer of vanA was assessed by filter mating. The only genetic difference between the vanA clusters of susceptible and resistant VVE was an ISL3-family element upstream of vanHAX, which silenced vanHAX gene transcription in susceptible VVE. Furthermore, the VVE had an insertion of IS1542 between orf2 and vanR that attenuated the expression of vanHAX Growth of susceptible VVE occurred after 24 to 72 h of exposure to vancomycin due to excision of the ISL3-family element. The vanA gene cluster was located on a transferable broad-host-range plasmid also detected in outbreak isolates with different pulsotypes, including one E. faecalis isolate. Horizontally transferable silenced vanA able to escape detection and revert into resistance during vancomycin therapy represents a new challenge in the clinic. Genotypic testing of invasive vancomycin-susceptible enterococci by vanA-PCR is advised.
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