Pivotal plasmids drive the global spread of CTX-M-27 in Escherichia coli

The detection rate of CTX-M-27-producing E. coli has increased worldwide in recent years although relatively little is known about the strains and vectors responsible for this increased isolation.To explore the evolution of CTX-M-27-producing E. coli in the past 20 years at three levels; genetic structure of the bla_CTX-M-27 locus, nature of carrying plasmids and types of host bacteria, we analysed 543 genomes of bla_CTX-M-27-positive E. coli isolated globally from 2003 to 2020.Results indicated that hospitalised patients are a major reservoir of bla_CTX-M-27 carrying isolates but there are a wide variety of other resistance genes, plasmid replicons and virulence factors carried by CTX-M-27-producing E. coli strains. There was a strong positive correlation between carriage of the bla_CTX-M-27 gene and the highly virulent clone-ST131 E. coli. IncF-type plasmids were the most common vector of bla_CTX-M-27 transmission with a subtype of F plasmids showing a tropism for specific sequence types of E. coli. The DNA transfer and replicon-stability regions of host plasmids showed evidence for significant evolution over time with deletion and truncation events associated with bla_CTX-M-27-carrying plasmids being stably maintained in specific host sequence types. Moreover, recently isolated bla_CTX-M-27-carrying plasmids were found to contribute to growth of host bacteria suggesting they have evolved to provide benefits to their host. IncF plasmids and the bla_CTX-M-27 locus also showed evidence for co-evolution, in particular, "Bridge" co-integrate structures flanked by IS26 were found in this study in IncF plasmids.Together, our results illustrate that bla_CTX-M-27 is present on various plasmids which are associated with epidemic host E. coli and it appears carriage of prevalent IncF bla_CTX-M-27-carrying plasmids are beneficial for the host. Complex genetic structures are under evolutionary pressure which promote the wide spread of bla_CTX-M-27 which is a global health threat.