Dynamical memory underlies prolonged plasmid persistence after transient antibiotic treatment

Abstract

Plasmids play critical roles in spreading and maintaining antimicrobial resistance (AMR). They often exhibit prolonged persistence upon antibiotic treatment, even when they impose 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 slow-down in plasmid abundance decay at high initial plasmid abundance, reminiscent of the ghost effect from nonlinear dynamical systems. Integrating theory, simulations, and quantitative experiments across clonal populations and multi-species bacterial communities, we demonstrate that a transient antibiotic pulse can eliminate plasmid-free cells and create a ghost state that extends plasmid persistence from days to months. Our research 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.