Stabilizing features of cefotaximase harbouring plasmids enable persistence in UK livestock

Extended-spectrum cephalosporinases (ESCs) confer resistance to a range of beta-lactam compounds, including many cephalosporins and have grown in prevalence since the early 2000s. ESCs are often disseminated via plasmids, which can also encode other genes that confer bacterial fitness. Until recently, detailed characterization of plasmids encoding antimicrobial resistance genes was limited by the technical ability to close plasmid genomes. Recent advances in long-read technology have simplified this problem, facilitating the characterization of the genetic structure of plasmids and their component genes. This study examined the genetic mechanisms that underpin the stability of the most common cefotaximase-encoding plasmids in Escherichia coli recovered from UK livestock between 2013 and 2020. The most common plasmid replicon types were IncF, IncI1 and IncX, and the predominant cefotaximases were bla _CTX-M-1, blaCTX-M-14, bla _CTX-M-15 and bla _CTX-M-55; in this study, we focused on IncI1 plasmids only which were most commonly associated with the cefotaximases in our dataset. Comparison of circularized plasmid genomes revealed that IncI1/bla _CTX-M-1 plasmids showed a high degree of genetic similarity to one another in the time period examined, as did IncI1/bla _CTX-M-14 plasmids, indicating stability of these plasmid genomes. Overall, our results indicate that IncI1/bla _CTX-M-1 plasmids carry genes promoting their maintenance in host E. coli and encode several genes that may enhance their fitness. Therefore, these plasmids may play an important role in the persistence of ESC resistance in E. coli isolated from One-Health compartments, despite nationwide reductions in cephalosporin usage in both humans and livestock.