The plasmidome associated with Gram-negative bloodstream infections: A large-scale observational study using complete plasmid assemblies

Samuel Lipworth (), William Matlock, Liam Shaw, Karina-Doris Vihta, Gillian Rodger, Kevin Chau, Leanne Barker, Sophie George, James Kavanagh, Timothy Davies, Alison Vaughan, Monique Andersson, Katie Jeffery, Sarah Oakley, Marcus Morgan, Susan Hopkins, Timothy Peto, Derrick Crook, A. Sarah Walker and Nicole Stoesser
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Samuel Lipworth: University of Oxford
William Matlock: University of Oxford
Liam Shaw: University of Oxford
Karina-Doris Vihta: University of Oxford
Gillian Rodger: University of Oxford
Kevin Chau: University of Oxford
Leanne Barker: University of Oxford
Sophie George: University of Oxford
James Kavanagh: University of Oxford
Timothy Davies: University of Oxford
Alison Vaughan: University of Oxford
Monique Andersson: Oxford University Hospitals NHS Foundation Trust
Katie Jeffery: Oxford University Hospitals NHS Foundation Trust
Sarah Oakley: Oxford University Hospitals NHS Foundation Trust
Marcus Morgan: Oxford University Hospitals NHS Foundation Trust
Susan Hopkins: United Kingdom Health Security Agency
Timothy Peto: University of Oxford
Derrick Crook: University of Oxford
A. Sarah Walker: University of Oxford
Nicole Stoesser: University of Oxford

Nature Communications, 2024, vol. 15, issue 1, 1-11

Abstract: Abstract Plasmids carry genes conferring antimicrobial resistance and other clinically important traits, and contribute to the rapid dissemination of such genes. Previous studies using complete plasmid assemblies, which are essential for reliable inference, have been small and/or limited to plasmids carrying antimicrobial resistance genes (ARGs). In this study, we sequenced 1,880 complete plasmids from 738 isolates from bloodstream infections in Oxfordshire, UK. The bacteria had been originally isolated in 2009 (194 isolates) and 2018 (368 isolates), plus a stratified selection from intervening years (176 isolates). We demonstrate that plasmids are largely, but not entirely, constrained to a single 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.

Date: 2024
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DOI: 10.1038/s41467-024-45761-7

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