The Evolution of Plasmids Carrying Multiple Resistance Genes: The Role of Segregation, Transposition, and Homologous Recombination

Abstract

We used a mathematical model and experiments with laboratory populations of Escherichia coli to examine conditions for the evolution of plasmids conferring resistance to multiple antibiotics. In our model and its experimental analogue, two different resistance genes are initially carried on separate plasmids, and recombination between the plasmids can generate a third element that carries both resistances. The environment is such that only cells carrying the two resistance genes can replicate. Our simulations predict that under these conditions, populations carrying a single plasmid with both resistance genes increase in frequency at a rate approximately equal to that at which the two-plasmid state decays by vegetative segregation. When the segregation rate is high, the pace of evolution is nearly independent of the rates of recombination and plasmid transfer or of whether the antibiotic is bacteriostatic or bacteriocidal. In the main, our experimental results are consistent with these predictions. When t...