Bacterial “Fossil Record” Reveals How a Superbug Rose to Dominance
Researchers have pieced together the genetic history of a hospital pathogen using samples dating back to the 1970s.
Hospital samples dating back to the 1970s have revealed how the deadly antimicrobial-resistant “superbug” Acinetobacter baumannii (A. baumannii) came to be a major global threat.
Analysis of bacterial isolates revealed that A. baumannii adapted in waves, with each wave producing bacteria better adapted to resist antibiotics than the previous wave.
The most successful A. baumannii lineage—international clone 2 (IC2)—became dominant in 2005. This coincides with when the bacteria acquired genes commonly associated with antimicrobial resistance (AMR).
The study, published in the journal Microbial Genomics, also describes how IC2 can be further split into at least four distinct groups. While groups one, two, and three represent incremental evolution of the A. baumannii chromosome, group four is distinct. It shows a parallel evolutionary history that the researchers believe may be in the early stages of expansion.
Details on how A. baumannii gradually accumulated AMR over time could inform future policies on antibiotic use and the development of new treatments for A. baumannii infections.
Mining the history of a notorious pathogen
A. baumannii thrives in hospital environments and can cause infections that are extremely difficult to treat with existing antibiotics. It is one of only four bacteria listed in the “critical” priority group in the World Health Organization’s Bacterial Priority Pathogen list.
“We wanted to understand how the genome of the bacterium has changed over the last 50 years and has resulted in the formidable pathogen we see today,” Dr. Benjamin Evans, lecturer in medical microbiology at the University of East Anglia’s Norwich Medical School, told Technology Networks.
To determine A. baumannii’s evolutionary history, the researchers utilized a set of 226 hospital samples dating from the 1970s to early 2000s. The samples were cultured in the lab, long-read sequenced, and assembled into high-quality chromosomes.
To build a more global picture, the researchers merged publicly available A. baumannii genomes, producing a dataset of 1,281 chromosomes derived from samples collected across 6 continents.
Bioinformatics tools were used to produce a detailed evolutionary tree from the dataset. This was then combined with antimicrobial resistance gene presence/absence data to track how changes in certain genes reshaped the bacteria over time.
This detailed analysis of evolutionary history was made possible by recent advances in genome sequencing.
“Bacterial genomes have lots of repeated sequences in them, which can make it hard to know what order the genome sequence should go in,” explained Evans. “With older genome sequencing technologies, this meant that the bacterial genomes would be made up of lots of different fragments, like pieces of a jigsaw that we didn’t know how to assemble.”
Genes associated with antibiotic resistance are often found on the boundaries between these “jigsaw pieces”, making it hard to understand how they relate to one another.
“Newer genome sequencing technologies are able to overcome this problem and allow us to produce complete bacterial chromosomes. This means we are able to see how different parts of the genome moved around and were gained and lost together over time,” Evans said.
The rise of a hospital superbug
The researchers identified the acquisition of oxa23 and the formation of Acinetobacter baumannii Genomic Resistance Island 3 (AbGRI3) around 2005 as turning points in the bacteria’s rise to dominance.
What is AbGRI3?
AbGRI3 is an area of the A. baumannii genome where many genes that make the bacterium resistant to antibiotics are clustered closely together.
The gene oxa23 produces an enzyme capable of breaking down carbapenems, the primary antibiotic used to treat A. baumannii. “The acquisition of this gene therefore rendered our primary therapeutic option ineffective,” stated Evans.
Similarly, the formation of AbGRI3 around the same time allowed A. baumannii to increase in prevalence. However, not all the genes in AbGRI3 are needed by the bacteria, and “around about 2015 it lost these genes, and we believe this efficiency benefited the bacterium and contributed to the further expansion of this pathogen,” Evans continued.
The team also found that the bacterium did not evolve as one uniform strain. Looking at patterns of antimicrobial resistance genes, the researchers found that A. baumannii can be divided into four groups.
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Groups one, two, and three emerged in sequence over time as A. baumannii slowly adapted to AMR selection. Group four is distinct in that it appears to have branched off independently.
Group four has seen an increase in isolation and sequencing since 2023, driven in part by pathogen surveillance programs in the United States. While this may be due to increased sampling, the researchers believe the similarities they’ve observed in patterns of expansion with groups two and three suggest that group four may be in the early stages of its own expansion.
It is worth noting that the historical samples used in the study show a bias towards the UK and Europe, with a notable lack of isolates from Asia and the Middle East, despite these regions having A. baumannii outbreaks in the early 2000s. This bias may have offset the date when a gene was believed to have first been acquired, if acquisition first occurred in one of the missing regions. Despite this, the historical chromosomes still provide insight into the evolution of A. baumannii that would have been difficult with pre-existing data.
Informing future policies for tackling AMR
The method used in the study could be applied to any bacterium. The limiting factor for the analysis is the availability of old bacterial isolates, which may have been lost over time.
“Any researchers who have held on to such collections of isolates will be able to analyze this bacterial ‘fossil record’ as we have done, and see how pathogens have evolved over time.” — Dr. Benjamin Evans.
Through understanding how and when A. baumannii became resistant to antibiotics, it's possible to see how healthcare practices have influenced its evolution. This could help inform policies on how we use antibiotics now and in the future.
“We can use these data to identify possible new parts of the bacterium to develop new drugs to target. Furthermore, identifying subtypes of a bacterium can allow us to assess how much risk that particular subtype might pose to a patient when causing an infection,” concluded Evans.
Reference: Neil M, Grenier F, Allard N, et al. New isolates from the 1970s to early 2000s provide insights into the evolution of Acinetobacter baumannii international clone 2 and its resistome. Microb Genom. 2026;12(7). doi: 10.1099/mgen.0.001752
Dr. Benjamin Evans is the group leader of the healthcare-associated pathogens research group in the Norwich Medical School at UEA. He completed his undergraduate degree and PhD at the University of Edinburgh, followed by postdoc positions at the University of Manchester and University of Liverpool. Evans’ first lecturing position was at Anglia Ruskin University, before moving to UEA in 2016.
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