Decades-old hospital samples have helped University of East Anglia (UEA) researchers uncover how a deadly antibiotic-resistant "superbug" quietly tightened its grip across the globe.
It lurked in hospital corridors for decades, largely unnoticed by the wider public.
But now an international team - including scientists at the Quadram Institute and in Canada and Mexico - have uncovered how one of the world's most feared superbugs rose to global dominance.
In a groundbreaking new study, researchers pieced together the genetic history of Acinetobacter baumannii - a notoriously stubborn hospital pathogen - using samples stretching back as far as the 1970s.
They found that this bacterium evolved and adapted quietly for decades, accumulating small changes that eventually made it resistant to antibiotics.
Lead researcher Dr Benjamin Evans, from UEA's Norwich Medical School, said: "We know that bacteria that cause infections in people can adapt to the antibiotics we use to treat them, rendering the antibiotics ineffective.
"We looked at a specific type of bacterium called Acinetobacter baumannii from the 1970s to the present day.
"This bacterium particularly thrives in hospital environments and can cause infections that are extremely difficult to treat - particularly for vulnerable patients.
"Understanding how it evolved into such a formidable threat is really important in stopping its spread. But until now, the genetic events behind this bacterium's success were poorly understood.
"What we found is that it has adapted in waves, with each wave producing bacteria that were better adapted to resist antibiotics than the previous wave.
"Our work provides one of the clearest pictures yet of how antibiotic resistance can accumulate gradually - and then suddenly tip the balance in favour of the pathogen.
"One thing is clear - this superbug didn't just appear. It was decades in the making, and it's still evolving."
How the research happened
Scientists made the breakthrough by combining decades-old bacterial samples with cutting-edge genome sequencing.
The team assembled a unique collection of 226 Acinetobacter baumannii samples dating from the 1970s to the early 2000s. These historical samples were carefully grown in the lab before their DNA was extracted, purified and sequenced using long-read Oxford Nanopore technology.
To build a global picture, the newly sequenced genomes were merged with more than 1,000 more recent genomes from six continents around the world.
Using high-performance computing, the scientists compared all 1,281 chromosomes and created a detailed evolutionary tree.
They paired this analysis with a comprehensive scan of antimicrobial resistance genes, tracking how these genes appeared, disappeared and reshaped the bacteria over time.
Tracking a drug-resistant threat
By aligning genetic changes with sample dates and locations, the team identified when key resistance traits emerged and how they spread globally.
This combined historical and modern approach allowed the team to reconstruct the pathogen's evolution over decades, revealing how it became a dominant, drug-resistant threat.
Dr Evans said: "Comparing patterns in the DNA sequence in the genomes allowed us to see how this bacteria has evolved over time, and how it has become more resistant to antibiotics."
"We found that it didn't suddenly emerge as a superbug. Instead, it crept into dominance - and by around 2005, it had become the leading lineage of A. baumannii worldwide."
But what happened around that time is key.
'Supercharged' bacteria
Researchers identified the acquisition of two major genetic elements - including a gene called oxa23, known for conferring resistance to powerful antibiotics - as a turning point.
This effectively supercharged the bacterium's ability to survive treatment. It became much harder to kill.
Not one bug - but many
The team also found that the bacterium in question isn't a single uniform strain. Instead, it can be divided into at least four distinct groups, each following its own evolutionary path.
Three of these groups appear to show a gradual, step-by-step evolution over time - like a slow genetic arms race against modern medicine. But a fourth group stands apart.
Dr Evans said: "This 'group 4' lineage appears to have branched off independently and is now being detected more frequently in recent samples. This is worrying because it means that a newer and potentially better adapted variant may already be on the rise.
Guiding policy
"This work is really important because understanding how antibiotic-resistant bacteria respond to changes in antibiotic use over time is essential for guiding policies on how we use antibiotics now and in the future.
"This is particularly important for bacteria like Acinetobacter baumannii. These bacteria represent a serious threat to healthcare systems worldwide, and we need new approaches to combat them otherwise infections will become untreatable."
This work was supported with funding from the Biotechnology and Biological Sciences Research Council (BBSRC), and in Canada from the New Frontiers in Research Fund, the Fonds de Recherche du Quebec, and the Canadian Institute for Advanced Research (CIFAR).
Dr Sadhana Sharma, UKRI-Biotechnology and Biological Sciences Anti-Microbial Resistance lead, said: "This study shows how a major hospital superbug evolved over decades, quietly adapting into distinct, drug-resistant groups and spreading globally.
"It underlines how antimicrobial resistance builds over time, and why understanding these changes is critical to staying ahead.
"It also highlights the importance of international collaboration, including with partners in Canada, and sustained BBSRC investment in fundamental bioscience to protect health, advance knowledge, improve lives and drive growth."
This study was led by UEA in collaboration with the Centre for Microbial Interactions and the Quadram Institute, both at Norwich Research Park, Université de Sherbrooke and the CISSS Montérégie-Centre, both in Québec (Canada), Universidad Nacional Autónoma de México (Mexico), and the Canadian Institute for Advanced Research in Toronto (Canada).
'New isolates from the 1970s to early 2000s provide insights into the evolution of Acinetobacter baumannii international clone 2 and its resistome' is published in the journal Microbial Genomics.
