Spreading Advantages of Coresident Plasmids bla(CTX-M)-Bearing IncFII and mcr-1-Bearing IncI2 in Escherichia coli

Two diverse conjugative plasmids can interact within bacterial cells. However, to the best of our knowledge, the interaction between bla(CTX-M)-bearing IncFII plasmid and mcr-1-carrying IncI2 plasmid colocated on the same bacterial host has not been reported. This study was initiated to explore the interaction and to analyze the reasons that these two plasmids are often coresident in multidrug-resistant Escherichia coli. To assess the interactions on plasmid stabilities, fitness costs, and transfer rates, we constructed two groups of isogenic derivatives, C600(FII), C600(I2), and C600(FII+I2) of E. coli C600 and J53(FII), J53(I2), and J53(FII+I2) of E. coli J53, respectively. We found that carriage of FII and I2 plasmids, independently and together, had not impaired the growth of the bacterial host. It was difficult for the single plasmid FII or I2 in E. coli C600 to reach stable persistence for a long time in an antibiotic-free environment, while the stability would be striking improved when they coresided. Meanwhile, plasmids FII and I2, whether together or apart, could notably enhance the fitness advantage of the host; moreover, E. coli coharboring plasmids FII and I2 presented more obvious fitness advantage than that carrying single plasmid FII. Coresident plasmids FII and I2 could accelerate horizontal cotransfer by conjugation. The transfer rates from a strain carrying coresident FII and I2 plasmids increased significantly when it mated with a recipient cell carrying one of them. Our findings highlight the advantages of coinhabitant FII and I2 plasmids in E. coli to drive the persistence and spread of plasmid-carried bla(CTX-M) and mcr-1 genes, although the molecular mechanisms of their coresidence warrant further study. IMPORTANCE More and more Enterobacteriaceae carry both bla(CTX-M) and mcr-1, which are usually located on IncFII-type and IncI2-type plasmids in the same bacterial host, respectively. However, the study on advantages of coresident plasmids in bacterial host is still sparse. Here, we investigated the stability, fitness cost, and cotransfer traits associated with coresident IncFII-type and IncI2-type plasmids in E. coli. Our results show that coinhabitant plasmids in E. coli are more stable, confer more fitness advantages, and are easier to transfer and cotransfer than a single plasmid IncFII or IncI2. Our findings confirm the advantages of coresident plasmids of bla(CTX-M)-bearing IncFII and mcr-1-bearing IncI2 in clinical E. coli, which will pose a serious threat to clinical therapy and public health.