Ecological memory of prolonged plasmid persistence after transient antibiotic exposure

Plasmids play critical roles in spreading and maintaining antimicrobial resistance (AMR). They often exhibit prolonged persistence after antibiotic treatment, even when they impose a substantial burden on their hosts. This persistence has been primarily attributed to rapid horizontal transfer or low plasmid cost. However, these mechanisms cannot account for the slow decay of burdensome plasmids with poor mobility. Here, we show that the decoupling of time scales between slow segregation loss and fast growth competition leads to a slowing of plasmid-abundance decay at high initial plasmid abundance. Integrating theory, simulations, and quantitative experiments across clonal populations and multispecies bacterial communities, we demonstrate that a transient antibiotic pulse can eliminate plasmid-free cells and create a segregation-loss bottleneck that extends plasmid persistence from days to weeks. Our study reveals a generalizable mechanism for the prolonged ecological memory of antibiotic exposure and underscores the need for proactive strategies to curb the spread of AMR. Zhou, Weiss and colleagues show that a brief antibiotic pulse can prolong plasmid persistence by removing plasmid-free competitors, creating an ecological memory that may sustain antimicrobial resistance.