A new study has provided an unprecedented high-resolution evolutionary map of Escherichia coli (E. coli), a significant step towards developing precision medicine for antibiotic-resistant infections.
Researchers from the Wellcome Sanger Institute, the University of Oslo, and UiT The Arctic University of Norway have leveraged large-scale long-read sequencing to track the genetic flow of E. coli plasmids – circular DNA structures responsible for the bacterium’s adaptability and resistance.
This revolutionary research has the potential to pioneer precision treatments for infections such as urinary tract infections (UTIs) by targeting specific bacterial traits rather than relying on broad-spectrum antibiotics.
Mapping bacterial evolution
By analysing 4,485 plasmid genomes from over 2,000 E. coli bloodstream samples collected over 16 years in Norway, scientists have successfully traced the genetic evolution of E. coli strains back 300 years.
This unprecedented mapping revealed the mechanisms behind plasmid-driven genetic exchanges and identified key barriers that impact gene transfer among bacterial strains.
Crucially, the study found that certain plasmids allow E. coli to produce bacteriocins – proteins capable of killing closely related bacteria.
This discovery could lead to novel precision medicine strategies using naturally occurring bacterial competition to combat antibiotic-resistant infections.
Harnessing bacterial competition for targeted treatments
Contrary to the notion that bacteria primarily fight against human treatments, E. coli strains are in constant competition with one another for survival in the human gut.
While most E. coli strains are harmless, some can cause severe infections if they enter the bloodstream, especially in immunocompromised individuals.
By understanding how plasmids contribute to antibiotic resistance and bacterial virulence, researchers suggest a paradigm shift in precision treatment strategies.
If less harmful E. coli strains can outcompete their more dangerous counterparts, they could potentially be introduced as a natural method to reduce infection risks.
The role of plasmids in antibiotic resistance
Plasmids are vital for bacterial evolution, acting as carriers of genes related to virulence, survival, and antibiotic resistance.
Their ability to transfer between bacterial strains complicates treatment efforts, as resistance can spread rapidly.
This study’s use of long-read sequencing allowed for precise tracking of these genetic exchanges, offering invaluable insights into how resistance traits emerge and persist.
A key finding was that multidrug resistance and bacteriocin production are rarely found in the same bacterial strains.
Laboratory tests confirmed that strains carrying highly effective bacteriocin-encoding genes could successfully inhibit non-carriers, including the most common E. coli strains in the UK.
Notably, these bacteriocin-producing strains effectively targeted multidrug-resistant E. coli, suggesting a potential alternative to traditional antibiotics.
Professor Pål Johnsen, co-senior author at the UiT The Arctic University of Norway, added: “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.”
The future of precision medicine
This evolutionary map represents a significant advancement in precision medicine, providing a resource for targeted bacterial treatment strategies.
By identifying the plasmids linked to harmful E. coli strains, future research could develop highly specific treatments that neutralise dangerous bacteria without disturbing beneficial microbiota.
Additionally, the ability to predict bacterial outbreaks based on historical plasmid tracking could transform public health strategies, enabling proactive infection control measures.
This study lays the groundwork for a new era in medicine – one where precision treatments replace blanket antibiotic use, reducing the rise of drug-resistant infections and revolutionising bacterial disease management.
