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 that constrains plasmid evolution. Here, we present evidence for the presence, consequences, and molecular basis of a conjugation-growth tradeoff across 40 plasmids derived from clinical Escherichia coli pathogens. We discover that most plasmids operate below a conjugation efficiency threshold for major growth effects, indicating strong natural selection for vertical transfer. Below this threshold, 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 greater share of host resources. Our results provide insight into evolutionary constraints directing plasmid fitness and strategies to combat the spread of antibiotic resistance.

Automated summary

Plasmid fitness is determined by vertical and horizontal transfer processes. While improvements in either mode of transfer can enhance plasmid spread and persistence, the metabolic cost of conjugation could limit plasmid evolution. Through the study of 40 plasmids from clinical E. coli pathogens, we uncover a conjugation-growth tradeoff and its consequences and molecular basis. Most plasmids operate below a threshold of conjugation efficiency for significant growth effects, indicating strong selection for vertical transfer. E. coli demonstrates remarkable growth tolerance to changes in conjugation efficiency below this threshold, which diminishes as nutrients become scarce and horizontal transfer consumes a greater share of host resources. Our findings provide insights into evolutionary constraints on plasmid fitness and strategies to combat antibiotic resistance spread.