Recombination and accessory genome turnover shaped the rise and decline of vanA Enterococcus faecium ST80 in Denmark.
10 affiliations
- 1School of the Environment, University of Windsor, Windsor, ON, N9B 3P4, Canada. [email protected].
- 2Great Lakes Institute for Environmental Research, University of Windsor, Windsor, ON, Canada. [email protected].
- 3WE SPARK Health Institute, Windsor, ON, Canada. [email protected].
- 4Department of Clinical Microbiology, Copenhagen University Hospital, Amager Hvidovre Hospital, Hvidovre, Denmark.
- 5Department of Gastroenterology, Copenhagen University Hospital, Hvidovre, Denmark.
- 6Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, Denmark.
- 7Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
- 8Department of Sequencing and Bioinformatics, Statens Serum Institut, Copenhagen, Denmark.
- 9Laboratory of Bacterial Evolution and Molecular Epidemiology, Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa (ITQB-NOVA), Oeiras, 2780-157, Portugal.
- 10Laboratory of Bacterial Evolution and Molecular Epidemiology, Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa (ITQB-NOVA), Oeiras, 2780-157, Portugal. [email protected].
Abstract
Background
Vancomycin-resistant Enterococcus faecium (VREfm) is a major cause of hospital-associated infections globally. In the Capital Region of Denmark, VREfm ST80 emerged as the dominant vanA-positive clone but declined significantly over the following decade.Methods
To investigate the genomic mechanisms underlying this epidemiological shift, we assembled and performed whole-genome sequencing and phylogenomic analysis of 334 ST80 isolates collected from colonisation (83%) and infection (17%) cases across nine hospitals in the region between 2012 and 2020.Results
Two major clusters (Clusters 1 and 2) and nine sub-clusters (1.A-G and 2.H-I) were identified. Sub-cluster-1.A (169/334) was the dominant lineage, accounting for 72% of isolates from 2012-2015. Isolates from 2016-2020 were distributed across all sub-clusters, indicating increasing diversification over time. Genetic variation 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. Accessory genome comparisons revealed sub-cluster-specific enrichment of resistance genes, including ermG (89% in 1.B), tet(S) (85% in 1.A), and tet(M) (88% in sub-cluster-1.B). Additionally, genes associated with biofilm formation, ABC transporters, and biosynthesis of polysaccharides, terpenoids, and aspartate were differentially enriched across the clusters. These genomic signatures may have contributed to niche adaptation and intra-clonal diversification. Plasmidome analysis showed increased diversity in later years, with the decline of Inc18 family plasmids (from 80 to 38%) and the rise of two new plasmids, coinciding with reduced clonal stability. Long-read hybrid assemblies uncovered mosaic phage-like plasmids harboring the vanA operon alongside ermB, aadE, and aph(3')-IIIa suggesting a unique mechanism for co-mobilization of antimicrobial resistance via transduction or conjugation. Despite the observed diversity, a continuous and sustained intra- and inter-hospital transmission and dissemination of this clone was evidenced by the small SNP difference (≤ 15 SNPs) between strains.Conclusions
This study showed the continuous hospital transmission and intra-clonal diversity of VREfm ST80. The dissemination, transmission and persistence dynamics of the vanA ST80 clone in Denmark may have been shaped by recombination events and gain/loss of genes involved in general metabolism, antibiotic resistance and virulence, and inter-clonal competition.
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BibTeX
@article{lawal2026recombination,
title = {{Recombination and accessory genome turnover shaped the rise and decline of vanA Enterococcus faecium ST80 in Denmark.}},
author = {Opeyemi U Lawal and Ingrid Maria Cecilia Rubin and Jose Alfredo Samaniego Castruita and Andreas Munk Petersen and Sarah Mollerup and Martin Schou Pedersen and Mariana Camoez and Nuno A Faria and Henrik Westh and Mette Pinholt and Maria Miragaia},
journal = {Genome medicine},
year = {2026},
month = aug,
doi = {10.1186/s13073-026-01747-2},
url = {https://europepmc.org/article/MED/42907904},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Recombination and accessory genome turnover shaped the rise and decline of vanA Enterococcus faecium ST80 in Denmark.
AU - Opeyemi U Lawal
AU - Ingrid Maria Cecilia Rubin
AU - Jose Alfredo Samaniego Castruita
AU - Andreas Munk Petersen
AU - Sarah Mollerup
AU - Martin Schou Pedersen
AU - Mariana Camoez
AU - Nuno A Faria
AU - Henrik Westh
AU - Mette Pinholt
AU - Maria Miragaia
PY - 2026
DA - 2026/08/01
JO - Genome medicine
DO - 10.1186/s13073-026-01747-2
UR - https://europepmc.org/article/MED/42907904
AB - Background Vancomycin-resistant Enterococcus faecium (VREfm) is a major cause of hospital-associated infections globally. In the Capital Region of Denmark, VREfm ST80 emerged as the dominant vanA-positive clone but declined significantly over the following decade.Methods To investigate the genomic mechanisms underlying this epidemiological shift, we assembled and performed whole-genome sequencing and phylogenomic analysis of 334 ST80 isolates collected from colonisation (83%) and infection (17%) cases across nine hospitals in the region between 2012 and 2020.Results Two major clusters (Clusters 1 and 2) and nine sub-clusters (1.A-G and 2.H-I) were identified. Sub-cluster-1.A (169/334) was the dominant lineage, accounting for 72% of isolates from 2012-2015. Isolates from 2016-2020 were distributed across all sub-clusters, indicating increasing diversification over time. Genetic variation 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. Accessory genome comparisons revealed sub-cluster-specific enrichment of resistance genes, including ermG (89% in 1.B), tet(S) (85% in 1.A), and tet(M) (88% in sub-cluster-1.B). Additionally, genes associated with biofilm formation, ABC transporters, and biosynthesis of polysaccharides, terpenoids, and aspartate were differentially enriched across the clusters. These genomic signatures may have contributed to niche adaptation and intra-clonal diversification. Plasmidome analysis showed increased diversity in later years, with the decline of Inc18 family plasmids (from 80 to 38%) and the rise of two new plasmids, coinciding with reduced clonal stability. Long-read hybrid assemblies uncovered mosaic phage-like plasmids harboring the vanA operon alongside ermB, aadE, and aph(3')-IIIa suggesting a unique mechanism for co-mobilization of antimicrobial resistance via transduction or conjugation. Despite the observed diversity, a continuous and sustained intra- and inter-hospital transmission and dissemination of this clone was evidenced by the small SNP difference (≤ 15 SNPs) between strains.Conclusions This study showed the continuous hospital transmission and intra-clonal diversity of VREfm ST80. The dissemination, transmission and persistence dynamics of the vanA ST80 clone in Denmark may have been shaped by recombination events and gain/loss of genes involved in general metabolism, antibiotic resistance and virulence, and inter-clonal competition.
SN - 1756-994X
ER -