Plasmid transfer and loss probabilities interactively determine antibiotic resistance spread in surface-associated bacterial biomass

Abstract

Plasmid transfer among bacteria is an evolutionary driver of the spread of antibiotic resistance. Surface-associated bacterial biomass is a hotspot for plasmid transfer due to the dense spatial packing of cells. Compared to plasmid dynamics within a single biomass unit, the determinants of plasmid transfer between discrete units are less understood. Yet, discrete units routinely physically collide with each other as they grow, such as in sparse biofilms. Here, we used individual-based modelling to quantitatively predict how the probabilities of plasmid transfer and loss affect plasmid spread between discrete bacterial colonies as they grow and physically collide into each other. We found that these factors have interactive effects on the extent of plasmid transfer and the subsequent proliferation of transconjugants. We further found that these effects are controlled by the spatial distance between the colliding colonies and the spatial positioning of plasmid-carrying cells along the collision boundary. We then experimentally tested our modelling predictions using strains of Pseudomonas stutzeri and Escherichia coli that can exchange an antibiotic resistance-encoding plasmid. Our study reveals that plasmid transfer between colliding biomass units is determined by the complex interplay between plasmid transfer, plasmid loss, and spatial constraints, expanding our understanding of plasmid dynamics.