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The first-of-its-kind in-depth bacterial evolutionary map could pave the way for the development of precision treatments for certain antibiotic-resistant infections, such as urinary tract infections. Researchers at the Wellcome Sanger Institute, the University of Oslo, UiT The Arctic University of Norway, and their collaborators, have developed a new way of using large-scale long-read sequencing data to investigate circular genetic structures called plasmids in the most commonly studied microbe, Escherichia coli ( E. coli ).
Through this, the team were able to track the flow of gene exchange, identify some of the barriers preventing this, and trace outbreaks of different E. coli strains to specific plasmids going back approximately 300 years. The study, published today (3 April) in Nature Communications , also uncovered a plasmid found in multiple strains of E.
coli that allows them to produce a toxin to kill other closely related bacteria, which could help inform future therapies for bacterial infections. This high-resolution resource allows the scientific community to investigate E. coli at a level which has not been previously possible, providing information that shows how plasmids co-evolve with E.
coli strains. By being able to understand and track which plasmids provide E. coli strains with certain traits, it could be possible to target these directly.
This could minimise the need for broad-spectrum antibiotic use, and in turn, lower the spread of treatment-resistant bacterial infections. Additionally, researchers suggest that if a strain that is less dangerous to humans can naturally outcompete a more dangerous strain, it could be introduced to help manage human health more holistically. Bacteria are often in competition with each other, fighting for the same habitable landscape, which in the case of E.
coli , is the human gut. Most strains of E. coli are harmless; however, if the bacterium gets into the bloodstream due to a weakened immune system, it can cause infection, which can range from mild to life-threatening.
While it often feels like the fight is with humans, E. coli bacteria are mostly competing with other strains for resources. It is this competition that leads to genetic adaptation, such as antibiotic resistance , which will help them survive in certain environments.
Bacteria are able to transfer genetic material, and therefore, certain traits via plasmids, which are circular pieces of DNA. Plasmids often carry genes for virulence, survival, or antibiotic resistance, improving the bacterium's fitness. Multiple plasmids are often found in bacterial cells, and due to their complex genetic composition and ability to share genes with the host cell chromosome, plasmids are incredibly difficult to track.
In this latest study, Sanger Institute researchers and their collaborators used long-read sequencing to create 4,485 plasmid genomes from over 2,000 E. coli bloodstream samples, all collected over 16 years in Norway 1 . From these newly-created genomes, they were able to map the plasmids linked to 216 different strains of E.
coli , including the four most common strains in the UK. Related Stories Diabetes fuels antibiotic resistance, worsening infections and treatment challenges New CRISPR-enriched metagenomics method for detecting antibiotic resistance genes in wastewater New class of antibiotic selectively targets gonorrhea bacterium Additionally, the team created a 2D-map showing where genetic material had been transferred horizontally between strains. This allowed them to map the co-evolution of plasmids and E.
coli strains back 300 years, illustrating that this is a highly conserved and useful method of genetic transfer. By unravelling the evolution of plasmids, the team were able to connect earlier global outbreaks of particular strains with the plasmids responsible and understand more about the factors that cause certain strains to spread, tracking those with pandemic-causing abilities. The researchers were also able to identify certain traits that tend not to be compatible.
For example, multi-drug resistance to antibiotics and the ability to produce a substance that kills other strains, known as bacteriocin, are not found in the same bacterial strains. Using extensive laboratory experiments, the team were able to verify that those carrying the most successful bacteriocin-encoding genes were able to efficiently inhibit all non-carriers, including the top four most common E. coli strains circulating in the UK.
Importantly, the inhibition was effective against all multi-drug resistant strains in the sample, suggesting that further research into these bacteriocins could lead to new ways of treating treatment-resistant bacterial infections in the future. This evolutionary map is a vital resource for the research community and paves the way for new precision treatments that could target specific plasmids. Additionally, future studies could use this resource to further understand the factors and spread of strains that are more harmful to humans, possibly predicting outbreaks of bacterial infections and helping inform new ways to limit them.
Dr Sergio Arredondo-Alonso, co-first author previously at the University of Oslo, said: "Our work unravels the evolution of E. coli plasmids. From this, we've started to uncover what traits can be found together, and what can't, such as antimicrobial resistance and the ability to create bacteriocin.
The discovery of how the bacteriocin-producing ability is distributed among E. coli also highlights the different approaches that strains take to outcompete their rivals. Understanding all the factors in E.
coli 's warfare adaptations could be used to inform new ways to limit or prevent the spread of unwanted bacterial strains." Bacterial evolution and adaptation often depend on plasmids to support the transfer of genes, and are shaped by environmental factors. Our evolutionary map enables us to start exploring this on a level that has not been possible before, by finally filling in the gaps of plasmid evolution over decades and centuries and providing a way of linking this to what was happening in the world at the time.
We have created a new resource to tackle antimicrobial-resistant E. coli which could inform new ways to help stop these strains from spreading." Professor Pål Johnsen, co-senior author at the UiT The Arctic University of Norway Professor Jukka Corander, co-senior author at the Wellcome Sanger Institute and the University of Oslo, said: "This is one of the most exciting research projects I've led.
It has created a vital resource that I hope supports the wider scientific community to uncover new ways to help tackle bloodstream infections, especially those that are resistant to treatment. By mapping the evolution of plasmids, this resource can help us understand the mechanisms of gene transfer and target the plasmids which carry genetic traits that are most harmful to humans. In the future, this could help develop precision therapies that would reduce the need for wide-spectrum antibiotics, which in turn, could lessen the spread of drug-resistant bacteria.
" Wellcome Trust Sanger Institute Arredondo-Alonso, S., et al . (2025).
Plasmid-driven strategies for clone success in Escherichia coli. Nature Communications . doi.
org/10.1038/s41467-025-57940-1 ..
