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Antibiotic Resistance Spread in Europe Informed by Bacterial Plasmid Sequencing

NEW YORK – A team from the UK, Germany, and Italy has demonstrated the value of interrogating sequence data from bacterial plasmids, along with chromosomal sequences, to identify antibiotic resistance genes and track their spread.

In a statement, co-senior and co-corresponding author David Aanensen, a genomic pathogen surveillance researcher affiliated with the Wellcome Genome Campus and Oxford University's Li Ka Shing Centre for Evolution, called plasmids "the missing parts of the puzzle" for following some forms of antibiotic-resistant bacteria.

For a study published in the Proceedings of the National Academy of Sciences on Wednesday, he and his colleagues used long-read sequence and assembly data for dozens of Klebsiella pneumoniae samples collected across Europe, along with phylogenetics and short-read sequences from 1,717 K. pneumoniae isolates previously profiled at European hospitals, to track bacterial plasmid and chromosome patterns behind the spread of carbapenemase enzyme-coding genes that boost resistance to carbapenem-based antibiotics.

"Analyzing the genetic sequences of both bacterial chromosomes and plasmids can give us a more detailed picture of how antibiotic resistance genes and mechanisms spread in a population," Aanensen said. "Genomic surveillance of bacteria should include plasmids and other mobile elements in order to tackle the rise in antibiotic-resistant infections."

The team's findings suggested plasmid-based carbapenemase gene spread is widespread and pointed to three main modes by which these plasmid-borne bacterial plasmids spread: a single antibiotic resistance-related plasmid such as the so-called "epidemic pOXA-48-like" plasmid that infiltrates several different bacterial strains, multiple resistance-related plasmids hopping in and out of individual high-risk bacterial clones, or carbapenem resistance that spreads via multiple plasmids and multiple bacterial strains.

"Knowing these transmission strategies enables tailoring of interventions, either to control the dominant plasmid, control the dominant strain, or in complicated situations, control both," co-senior author Hajo Grundmann, an infection prevention and hospital epidemiology researcher at the University of Freiburg in Germany, said in a statement.

Bacterial plasmids tend to get left out in pathogen surveillance programs that hinge on relatively low-resolution molecular profiling methods, the team noted, while the K. pneumoniae sequence data revealed the possibility of achieving a more refined understanding of pathogen and antibiotic resistance spread by incorporating additional long-read sequence data.

"Taken altogether, these results reveal the diverse trajectories of antibiotic resistance genes in clinical settings," the authors wrote, arguing that the broader approach of the study "provides a framework for the much needed incorporation of plasmid data into genomic surveillance systems, an essential step toward a more comprehensive understanding of resistance spread."