Acinetobacter baumannii superbug evolved gradually to global dominance

Acinetobacter baumannii superbug evolved gradually to global dominance

A deadly hospital pathogen has achieved global dominance not through a sudden emergence, but through a decades-long process of quiet adaptation. Researchers from the University of East Anglia (UEA) have uncovered the genetic history of Acinetobacter baumannii, revealing how the "superbug" accumulated small genetic changes to render antibiotics ineffective.

The bacterium thrives in hospital environments and creates infections that are extremely difficult to treat, according to lead researcher Dr Benjamin Evans of UEA’s Norwich Medical School. The study indicates that the pathogen adapted in waves, with each subsequent wave producing bacteria better equipped to resist medical treatments than the previous one.

To reconstruct this timeline, an international team including scientists from the Quadram Institute and partners in Mexico and Canada combined historical samples with modern data. The team assembled 226 samples dating from the 1970s to the early 2000s. After growing these samples in a lab, the researchers used long-read Oxford Nanopore technology to extract and sequence their DNA.

These historical genomes were merged with more than 1,000 recent genomes collected from six continents. Using high-performance computing, the scientists compared 1,281 chromosomes to build a detailed evolutionary tree and scan antimicrobial resistance genes.

The findings show the bacterium "crept into dominance" over several decades. By around 2005, it had established itself as the leading lineage of A. Baumannii worldwide. Researchers identified a critical turning point when the bacterium acquired two major genetic elements, including a gene known as oxa23. This gene confers resistance to powerful antibiotics, effectively supercharging the pathogen's ability to survive treatment.

"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,"

Dr Benjamin Evans, UEA’s Norwich Medical School, via Technology Networks

The analysis revealed that A. Baumannii is not a single uniform strain but is divided into at least four distinct groups. Three of these groups followed a gradual, step-by-step evolutionary path. However, a fourth group branched off independently. Dr Evans noted that this "group 4" lineage is being detected more frequently in recent samples, suggesting a newer and potentially better-adapted variant is currently on the rise.

Dr Gemma Langridge of the Quadram Institute stated that accessing and sequencing strains from 50 years ago was a crucial element of the study, as it allowed the team to detect when specific subtypes emerged and how they spread globally.

The research was led by UEA in collaboration with the Universidad Nacional Autónoma de México, the Canadian Institute for Advanced Research in Toronto, the CISSS Montérégie-Centre and Université de Sherbrooke in Québec, and the Quadram Institute and Centre for Microbial Interactions at Norwich Research Park.

Funding for the project was provided by the Biotechnology and Biological Sciences Research Council (BBSRC) in the UK, as well as the Fonds de Recherche du Quebec, the New Frontiers in Research Fund, and the Canadian Institute for Advanced Research (CIFAR) in Canada.

Dr Sadhana Sharma, the UKRI-Biotechnology and Biological Sciences Anti-Microbial Resistance lead, said the study highlights how antimicrobial resistance builds over time and emphasizes the necessity of international collaboration and fundamental bioscience investment to protect global health.

The study, titled New isolates from the 1970s to early 2000s provide insights into the evolution of Acinetobacter baumannii international clone 2 and its resistome, was published in the journal Microbial Genomics. Researchers maintain that understanding these evolutionary responses is essential for guiding future policies on antibiotic use to prevent infections from becoming entirely untreatable.