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Pre- and postantibiotic epoch: The historical spread of antimicrobial resistance | Science

**Understanding the Evolution of Antimicrobial Resistance: The Role of Plasmids Before Antibiotics**

Plasmids, small circular DNA molecules found in bacteria, have become the primary vectors of antimicrobial resistance (AMR), posing significant challenges to public health worldwide. As the use of antibiotics surged in the mid-20th century, the evolution of these plasmids accelerated, enabling bacteria to acquire and disseminate resistance genes more rapidly. However, our understanding of how industrialization and the widespread use of antibiotics have influenced the evolution of these plasmids is hampered by a lack of data from the period before antibiotics were introduced. This gap in knowledge, referred to as the “paucity of data predating the antibiotic era” (PAE), limits our ability to fully comprehend the historical context of AMR and its current implications.

Recent research aims to bridge this knowledge gap by investigating the evolutionary history of plasmids and their role in AMR prior to the antibiotic boom. By analyzing ancient bacterial genomes and plasmids from various ecological niches, scientists are uncovering patterns of resistance that predate the clinical use of antibiotics. For example, studies have shown that certain resistance genes were already present in environmental bacteria long before the first antibiotics were synthesized, suggesting that the natural selection pressures exerted by environmental factors may have played a significant role in shaping the plasmid landscape. This revelation underscores the complexity of AMR, highlighting that while human activities have exacerbated the problem, the roots of resistance are deeply embedded in the natural world.

Additionally, understanding the evolution of plasmids and their resistance mechanisms can inform strategies to combat AMR. By identifying the environmental reservoirs of resistance genes, researchers can develop targeted interventions to mitigate the spread of these plasmids in clinical settings. Furthermore, this knowledge could aid in the development of new antibiotics that are less likely to be undermined by existing resistance mechanisms. As the global community grapples with the rising tide of AMR, delving into the historical context of plasmids and their evolution offers critical insights that could shape future public health strategies and antibiotic stewardship programs. Ultimately, addressing the challenges posed by antimicrobial resistance requires a comprehensive understanding of both the past and present dynamics of bacterial evolution.