Vertical and horizontal gene transfer tradeoffs direct plasmid fitness

Plasmid fitness is directed by two orthogonal processes--vertical transfer through cell division and horizontal transfer through conjugation. When considered individually, improvements in either mode of transfer can promote how well a plasmid spreads and persists. Together, however, the metabolic cost of conjugation could create a tradeoff between the two and constrain plasmid evolution. Here we preset evidence for the presence, consequences, and molecular basis of a conjugation-growth tradeoff across 40 plasmids derived from clinical E. coli pathogens. We discover that most plasmids avoid a tradeoff by operating below a conjugation efficiency threshold for major growth effects, indicating strong selection for vertical transfer. In this region, E. coli demonstrates a remarkable growth tolerance to over four orders of magnitude change in conjugation efficiency. This tolerance fades as nutrients become scarce and horizontal transfer attracts a larger share of host resources. Our results provide insight in evolutionary constraints directing plasmid fitness and strategies to combat the spread of antibiotic resistance.