How Vancomycin-Resistant Enterococcus Evolved in a Danish Hospital

Vancomycin-resistant Enterococcus faecium is listed by the World Health Organization—in its 2024 Bacterial Priority Pathogens List—as one of the highest-priority bacteria.

In a new study published in Genome Medicine, researchers from Instituto de Tecnologia Química e Biológica António Xavier from NOVA University of Lisbon (ITQB NOVA), in Portugal, investigated the genetic mechanisms behind the rise and fall of the dominant vancomycin-resistant Enterococcus faecium clone (VREfm ST80) from 2012 to 2020 in Danish hospitals. The team assembled and performed whole-genome sequencing and phylogenomic analysis of 334 ST80 isolates collected from colonization (83%) and infection (17%) cases across nine hospitals in the region between 2012 and 2020.

The results identified two major clusters (Clusters 1 and 2) and nine sub-clusters (1.A–G and 2.H–I). Sub-cluster-1.A (169/334) was the dominant lineage, accounting for 72% of isolates from 2012–2015. The isolates from 2016–2020 “were distributed across all sub-clusters, indicating increasing diversification over time.”

Genetic variation, the authors write, was “driven by accumulation of mutations, recombination and gain/loss of accessory genes and plasmids.” Eight recombination hotspots were identified in core genes involved in cell wall synthesis, phosphotransferase systems, amino-acid biosynthesis, and several transporters.

This work is published in Genome Medicine in the paper, “Recombination and accessory genome turnover shaped the rise and decline of vanA Enterococcus faecium ST80 in Denmark.”

The team also found that this bacterial clone carried a mosaic phage-like plasmid element that made it resistant to several antibiotics at once. The element harbored the vanA operon with ermB, aadE, and aph(3’)-IIIa suggesting “a unique mechanism for co-mobilization of antimicrobial resistance via transduction or conjugation.”

“Using any one of those antibiotics can select for bacteria carrying the whole package, including vancomycin resistance,” explains Maria Miragaia, PhD, leader of the Bacterial Evolution and Molecular Epidemiology lab at ITQB NOVA. “This means that simply reducing vancomycin use may not be enough to reduce vancomycin-resistant bacteria if other linked antibiotics are still being used,” she adds.

The study suggests that targeting the strategies that helped the clone persist—forming biofilms, altering its outer surface, and using alternative sugars in the gut—could help to clear these resistant bacteria from the gut and reduce their spread in hospitals.

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