The mobilome associated with Gram-negative bloodstream infections: A large-scale observational hybrid sequencing based study

Plasmids carry genes conferring antimicrobial resistance (AMR), and other clinically important traits; their ability to move within and between species may provide the machinery for rapid dissemination of such genes. Existing studies using complete plasmid assemblies, which are essential for reliable inference, have been small and/or limited to those carrying particularly antimicrobial resistance genes (ARGs). In this study, we sequenced 1,880 complete plasmids from 738 isolates from bloodstream infections (BSI) in 2009 (194 isolates) and 2018 (368 isolates) in Oxfordshire, UK, plus a stratified selection from intervening years (176 isolates). We demonstrate that plasmids are largely, but not entirely, constrained to host species, although there is substantial overlap between species of plasmid gene-repertoire. Most ARGs are carried by a relatively small number of plasmid groups with biological features that are predictable. Plasmids carrying ARGs (including those encoding carbapenemases) share a putative backbone of core genes with those carrying no such genes. These findings suggest that future surveillance should, in addition to tracking plasmids currently associated with clinically important genes, focus on identifying and monitoring the dissemination of high-risk plasmid groups with the potential to rapidly acquire and disseminate these genes.