Positive selection inhibits plasmid coinfection

Plasmids play an important role in bacterial evolution by transferring niche adaptive functional genes between lineages driving genomic diversification. Bacterial genomes commonly contain multiple plasmid replicons (i.e., plasmid coinfection) which could fuel adaptation by increasing the range of gene functions available to selection and allowing their recombination. However, plasmid coinfection is difficult to explain because the acquisition of plasmids typically incurs high fitness costs for the host cell. Here, we show that plasmid coinfection was stably maintained without positive selection for plasmid-encoded gene functions and was associated with compensatory evolution to reduce fitness costs. By contrast, plasmid coinfection was unstable in the presence of positive selection. This arose despite compensatory evolution because of redundancy and differential fitness benefits provided by the plasmids, which drove retention of only the more beneficial plasmid. These data suggest that selection for plasmid fitness benefits is more efficient than selection against plasmid fitness costs. Widespread plasmid coinfection may therefore reflect rare positive selection in nature or require non-redundancy of accessory gene functions among coinfecting plasmids.