In a groundbreaking study recently published in Science, an international team of researchers has unveiled critical insights into the genetic mechanisms propelling the global spread of multidrug resistance among bacterial pathogens. By meticulously analyzing an unprecedented dataset comprising more than 40,000 plasmids extracted from bacterial specimens collected over the past century across six continents, scientists have mapped the evolutionary journey of antimicrobial resistance with an unprecedented historical scope. This comprehensive investigation was spearheaded by experts from the Wellcome Sanger Institute, the University of Bath, and the UK Health Security Agency, among other collaborators.
Plasmids, which are extrachromosomal DNA elements capable of horizontal transfer between bacterial cells, play a pivotal role in disseminating genes that confer resistance to antibiotics. The study reveals that a relatively small subset of these plasmids functions as major vectors, driving the multidrug resistance crisis troubling modern medicine. Historically, plasmids did not initially carry resistance genes; instead, their acquisition of antimicrobial resistance traits occurred after the widespread introduction of antibiotics in the 20th century, underscoring the profound impact of human pharmaceutical practices on bacterial evolution.
By tapping into bacterial collections dating back to 1917, predating the antibiotic era, researchers traced the origins and evolutionary trajectories of plasmids pivotal to current resistance trends. They discovered that ancestral plasmids lacked resistance genes but gradually incorporated these genetic sequences in response to selective pressures imposed by antibiotic usage. These evolutionary adaptations have culminated in “modern plasmids” highly adept at conferring bacterial resistance not only to early-line treatments but also to critical last-resort antibiotics, amplifying the threat to global public health.
The team developed an evolutionary model that categorizes plasmid trajectories into three distinct pathways. The first involves the incremental acquisition of antimicrobial resistance genes into existing plasmid frameworks. The second pathway entails the fusion of distinct plasmids, resulting in composite plasmids that exhibit enhanced transferability across diverse bacterial species. The third pathway, less directly implicated in resistance dissemination, involves plasmid degradation and gene fragment recycling within bacterial populations. Both the gene insertion and plasmid fusion pathways have given rise to the most clinically significant resistant plasmids observed today.
A striking discovery was the demonstration that fusion-derived plasmids exhibit broad host ranges, facilitating the interspecies horizontal gene transfer of resistance determinants. This finding highlights the adaptive versatility of plasmids and the formidable challenge they pose in controlling the spread of resistance. Targeting these “super plasmids” harboring multiple resistance genes might pave the way for innovative therapeutic strategies aimed at curbing multidrug-resistant infections that currently cause over a million deaths annually worldwide.
Crucially, the model developed extends beyond retrospective insight, providing a predictive framework for plasmid evolution over the next century. This approach could enable epidemiologists and public health officials to anticipate emerging resistance patterns and infectious disease outbreaks with greater accuracy. Consequently, it offers a vital tool to guide effective stewardship of antibiotic use and bolster global efforts in curbing antimicrobial resistance proliferation.
Dr. Adrian Cazares, lead author from the Wellcome Sanger Institute, emphasized the transformative nature of these findings on our understanding of bacterial adaptation. “Our research uncovers how antibiotic use has reshaped plasmid genetics, turning a minority into highly efficient agents of resistance spread,” he explained. Such evolutionary pressures, largely anthropogenic, underscore the urgency of reevaluating antibiotic deployment policies.
Complementing this, Professor Zamin Iqbal of the University of Bath highlighted the intricate evolutionary dynamics of plasmids, including slow genetic drift, plasmid fusion events, and genetic recycling. These trends illustrate how microbial genomic plasticity fosters resilience under selective pressures, with human antibiotic consumption acting as a dominant force influencing plasmid diversity and functionality.
Furthermore, Dr. Sarah Alexander from the UK Health Security Agency praised the collaboration’s integration of historical bacterial archives, such as the Murray Collection, that, through rigorous preservation techniques, ensured faithful genetic representations of early 20th-century bacterial strains. This enabled the team to conduct authentic genomic comparisons across an expansive temporal scale, anchoring their evolutionary model in empirical data.
Professor Nick Thomson, co-senior author at the Wellcome Sanger Institute, reflected on the importance of combining historical microbiological archives with modern genomics. The decades-spanning samples illuminated molecular events underlying resistance emergence, offering a rare glimpse into the evolutionary mechanisms that continue to challenge contemporary medicine. The detailed understanding of plasmid evolution could eventually inform targeted interventions aimed at halting the unstoppable march of antibiotic resistance genes.
The societal implications of this research are profound. With antibiotic resistance threatening modern therapeutic paradigms, uncovering the genetic basis and evolution of resistance vectors is essential for developing rational strategies to mitigate their spread. Plasmid-targeted therapies may provide a novel frontier, accompanying traditional antibiotic treatments, that could safeguard efficacy and extend the lifespan of existing drugs.
This study exemplifies the power of integrated multidisciplinary science—melding genomics, evolutionary biology, microbiology, and epidemiology—in addressing one of humanity’s most pressing health crises. As antibiotic resistance continues to evolve rapidly, this research offers both a cautionary tale of past human impacts on microbial genomes and a hopeful pathway for future scientific and clinical innovation.
The findings underscore the urgent need for global coordinated action in antibiotic stewardship, infection control, and ongoing surveillance of resistance elements. By unveiling the molecular players driving multidrug resistance dissemination, researchers empower the medical community with knowledge critical for designing next-generation interventions to protect public health.
Subject of Research: Genetic mechanisms and evolutionary pathways driving the spread of multidrug resistance plasmids in bacteria over the past century.
Article Title: Pre and Post Antibiotic Epoch: The Historical Spread of Antimicrobial Resistance
News Publication Date: 25 September 2025
Web References:
References:
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.
Naghavi, M., et al. (2024). Global burden of bacterial antimicrobial resistance 1990–2021: a systematic analysis with forecasts to 2050. The Lancet.
Keywords: Antibiotic resistance, Drug resistance, Bacteria, Plasmids, Mobile genetic elements, Evolutionary biology
