(Press-News.org) The genetic culprits responsible for the spread of multidrug resistance (MDR) in bacteria have been identified by new research mapping 100 years of bacterial evolution.
Experts at the Wellcome Sanger Institute, the University of Bath, the UK Health Security Agency (UKHSA) and their collaborators1, analysed over 40,000 plasmids from historical and present-day bacterial samples taken across six continents, the largest dataset of its kind.
Plasmids are transferable structures in bacteria that allow different strains to share genetic information. In this study, published today (25 September) in Science, researchers found that a minority of plasmids causes most of the multidrug resistance in the world. In the future, developing ways to target these could lead to new therapies to combat treatment-resistant infections worldwide.
Currently, treatment-resistant infections cause at least one million deaths worldwide every year, with this number expected to rise2. While some bacteria and fungi carry antimicrobial resistance (AMR) genes naturally, the emergence and spread of MDR and AMR genes has been consistently linked to the use of antibiotics.
In this study, researchers were able to analyse bacterial samples from as far back as 1917, a time before the discovery of antibiotics. The team found that the ancestral plasmids that went on to become global spreaders of AMR genes did not contain resistance genes initially. They evolved to gain this resistance as the use of antibiotics grew. Their descendants, a relatively small group of modern plasmids, now confer resistance to both first-line and last-resort antibiotics, making them a huge threat to human health.
By diving into the last 100 years of bacterial history, the team also developed a model for plasmid evolution, highlighting the three distinct pathways plasmids can take.
The modern plasmids that contain MDR genes rose from two of these pathways. Either they were formed by AMR genes being inserted into an existing plasmid structure, or these plasmids were the result of fusion with another plasmid. The plasmids formed by fusion are also highly transferable between different species of bacteria.
As these plasmids are found across multiple different bacterial species, developing ways to target the AMR-carrying plasmids could lead to new therapies to combat multiple treatment-resistant infections worldwide.
Additionally, the model developed to explain the last 100 years of evolution could help predict how the next 100 years may go. This could help predict outbreaks and patterns of infectious disease and be used to inform public health strategies to stop the spread of infectious disease.
Dr Adrian Cazares, first author at the Wellcome Sanger Institute, said: “Plasmids are key drivers of bacterial survival against antibiotics. By going back in time through unique historical collections, we reveal how plasmids adapted to the antibiotic era and the evolutionary journey that transformed a minority of them into the global multidrug-resistant vectors driving the antimicrobial resistance crisis we face today. Our findings show that the widespread use of antibiotics fundamentally reshaped the genetic landscape of plasmids, and the way bacteria fight against antimicrobial treatment, and are a stark reminder that our actions have a profound and lasting impact on bacterial evolution.”
Professor Zamin Iqbal, co-senior author at the Milner Centre for Evolution, University of Bath, said: “Our research combines historical and modern-day data to give a new perspective on the evolutionary lifestyles that different plasmids can have, whether this be changing slowly, completely merging with other plasmids, or disappearing and leaving genetic fragments that are then 'recycled for parts’. Through our research, we can see the impact of human antibiotic use and the shadow of other selective forces, which also challenge bacteria and their plasmids.”
Dr Sarah Alexander, UKHSA lead for the study, said: “This groundbreaking study builds on a longstanding and successful collaboration between The National Collection of Type Cultures (NCTC) and the Wellcome Sanger Institute. The generous donation of the Murray Collection to the NCTC enabled us to conserve these irreplaceable bacterial strains. DNA analysis of our strains has shown how NCTC’s stringent preservation methods have ensured the bacteria have not changed since they were deposited, even over many decades. These exciting findings help us to better understand the origins of antimicrobial resistance and could play a role in helping us tackle the global spread of resistant infections over years to come.”
Professor Nick Thomson, co-senior author at the Wellcome Sanger Institute, said: “This research builds on the rich and leading role the UK has played in the discovery and development of antibiotics for the treatment of human and animal infections. Here, we combined expertise across institutes, teaming up with the longest-running publicly owned biological archive in the world. Thanks to this, we were able to use unique historical samples to glimpse at the molecular events behind one of the most significant challenges facing us today — untreatable infections. By uncovering the rules of plasmid evolution, it could be possible, in the future, to develop rational approaches to target the spread of antibiotic resistance genes, the consequences of which touch all our lives at one point or another.”
ENDS
Contact details:
Rachael Smith
Press Office
Wellcome Sanger Institute
Cambridge, CB10 1SA
07827979492
Email: press.office@sanger.ac.uk
Notes to Editors:
This was a highly collaborative project including experts at the Wellcome Sanger Institute, EMBL’s European Bioinformatics Institute (EMBL-EBI), the University of Cambridge, the University of Oxford, the UK Health Security Agency, the University of Bath, and the London School of Health and Tropical Medicine. A full author and affiliations list can be found in the publication.
Naghavi, Mohsen et al. (2024) ‘Global burden of bacterial antimicrobial resistance 1990–2021: a systematic analysis with forecasts to 2050’. The Lancet. Available at: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)01867-1/fulltext
Publication:
A. Cazares, W. Figueroa, D. Cazares, et al. (2025) ‘Pre and Post antibiotic epoch: the historical spread of antimicrobial resistance’. Science. DOI: 10.1126/science.adr1522
Funding:
This research was part-funded by Wellcome. A full acknowledgement list can be found in the publication.
Selected websites:
About the University of Bath
The University of Bath is one of the UK's leading universities, recognised for high-impact research, excellence in education, an outstanding student experience and strong graduate prospects.
We are ranked among the top 10% of universities globally, placing 132nd in the QS World University Rankings 2026.
We are ranked in the top 10 in all of the UK’s major university guides.
The University achieved a triple Gold award in the last Teaching Excellence Framework 2023, the highest awards possible, for both the overall assessment and for student outcomes and student experience. The Teaching Excellence Framework (TEF) is a national scheme run by the Office for Students (OfS).
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The Wellcome Sanger Institute is a world leader in genomics research. We apply and explore genomic technologies at scale to advance understanding of biology and improve health. Making discoveries not easily made elsewhere, our research delivers insights across health, disease, evolution and pathogen biology. We are open and collaborative; our data, results, tools, technologies and training are freely shared across the globe to advance science.
Funded by Wellcome, we have the freedom to think long-term and push the boundaries of genomics. We take on the challenges of applying our research to the real world, where we aim to bring benefit to people and society.
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END
Capturing 100 years of antibiotic resistance evolution
2025-09-25
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