Mobile genetic elements (MGEs) are primary facilitators in the global spread of antibiotic resistance. Here, we present novel ecological and evolutionary perspectives to understand and manage these elements: as selfish entities that exhibit biological individuality, as pollutants that replicate and as invasive species that thrive under human impact. Importantly, each viewpoint suggests new means to control their activity and spread. When seen as biological individuals, MGEs can be regarded as therapeutic targets in their own right. We highlight promising conjugation-inhibiting compounds that could be administered alongside antibiotic treatment. Viewed as pollutants, sewage treatment methods could be modified to efficiently remove antimicrobials and the resistance genes that they select. Finally, by recognizing the invasive characteristics of MGEs, we might apply strategies developed for the management of invasive species. These include environmental restoration to reduce antimicrobial selection, early detection to help inform appropriate antibiotic usage, and biocontrol strategies that target MGEs, constituting precision antimicrobials. These actions, which embody the One Health approach, target different characteristics of MGEs that are pertinent at the cellular, community, landscape and global levels. The strategies could act on multiple fronts and, together, might provide a more fruitful means to combat the global resistance crisis. This article is part of the theme issue 'The secret lives of microbial mobile genetic elements'.
Keywords: One Health; antibiotic pollution; antimicrobial resistance; horizontal gene transfer; mobile DNA.