IncC plasmid genome rearrangements influence the vertical and horizontal transmission tradeoff in Escherichia coli

Literature has previously described an evolutionary tradeoff between vertical (host growth rate) and horizontal (plasmid conjugation) transmissions, contributing to global plasmid fitness. As conjugative IncC plasmids are especially important for the spread of multidrug resistance (MDR), in an extremely broad range of bacterial hosts, we investigated vertical and horizontal transmissions of two pST3 IncC plasmids according to their backbones and MDR-region rearrangements, upon plasmid entry into a new host. We observed plasmid genome rearrangements after conjugation in three natural Escherichia coli clinical strains, varying from null to high number depending on the plasmid, but all occurring in the MDR-region. The plasmid burden on bacterial fitness depended more on the strain background than on the structure of the MDR-region, rearrangements appearing to have no impact. Besides, we observed a statistically significant increase in plasmid transfer rate, from ancestral host to new clinical recipient strains, when the IncC plasmid was rearranged. Finally, we investigated the evolutionary tradeoff of the IncC plasmid during the critical period of plasmid establishment in single K-12 bacterial host, by comparing host bacteria harboring the rearranged or non-rearranged IncC plasmid. Plasmid rearrangements strongly improved conjugation efficiency with no negative growth effect. Our findings indicate that the flexibility of the MDR-region of the IncC plasmids can promote their dissemination, and provide diverse opportunities to capture new resistance genes, especially in an environment subject to selection pressure. In a broader view, they reveal how the vertical-horizontal transmission tradeoff can be manipulated by the plasmid to improve its fitness.