Vancomycin-resistant Enterococcus faecium is listed by the World Health Organization as one of the highest-priority bacteria in its 2024 Bacterial Priority Pathogens List, ahead of MRSA , due to its ability to transfer resistance genes between humans, animals, and the environment.
Clonal replacement is common in hospital settings: high-risk bacterial lineages emerge, spread, and are eventually replaced. But why a once-successful clone loses its advantage has remained unclear.
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, and collaborators, investigated the genetic mechanisms behind the rise and fall of a vancomycin-resistant Enterococcus faecium clone from 2012 to 2020 at a danish hospital.
Their results showed that this epidemic clone o wed its dominance over the years to a stable, well-adapted genome carrying key plasmids (small circular DNA molecules) and accessory genes that helped it survive. These genes facilitated its persistence both in the gut and on hospital surfaces , allowing it to resist antibiotics, use alternative sugars, modify its outer envelope, and form biofilms , highly organised bacterial communities that attach to surfaces and are harder to eliminate. However, during its rise, it rarely recombined, or “shuffled” its DNA .
This challenges the common assumption that epidemic success depends on genomic plasticity. In this case, researchers saw the opposite: the clone became dominant because its genome remained stable. In contrast, when its genome started to diversify, the clone declined in the hospital.
The same features that initially helped the clone’s success were also those it lost as it declined. This is the case of genes linked to antibiotic resistance and the metabolism of alternative sugars. Moreover, some of its descendants acquired the ability to produce bacteriocins , small antimicrobial molecules that bacteria use to inhibit nearby competitors, giving them an additional advantage and ultimately contributing to the demise of their ancestral clone.
The team also found that this bacterial clone carried a genetic “super-tool” that made it resistant to several antibiotics at once . This element looked like a mix between a bacterial virus and a plasmid and could carry and pass on multiple resistance genes together. “Using any one of those antibiotics can select for bacteria carrying the whole package, including vancomycin resistance”, explains Maria Miragaia , leader of the Bacterial Evolution and Molecular Epidemiology lab at ITQB NOVA and senior author of the study. “ This means that simply reducing vancomycin use may not be enough to reduce vancomycin-resistant bacteria if other linked antibiotics are still being used ”, the researcher adds.
“Hospitals often only notice and respond to these clones once they have already spread widely,” explains Opeyemi Lawal , former PhD student at ITQB NOVA and now at Windsor University in Canada. “ By understanding why this clone declined in the hospital, we can identify its weak points and use that knowledge to control similar multidrug-resistant bacteria in the future.”
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.
Genome Medicine
Recombination and accessory genome turnover shaped the rise and decline of vanA Enterococcus faecium ST80 in Denmark
18-Aug-2026