The plasmidome associated with Gram-negative bloodstream infections: A large-scale observational study using complete
Samuel Lipworth1,2, William Matlock3, Liam Shaw4
1Nuffield Department of Medicine, University of Oxford, Oxford, UK. samuel.lipworth@ndm.ox.ac.uk.
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.
Insights
This study analyzed 1,880 plasmids from bloodstream infections, revealing that most antimicrobial resistance genes (ARGs) reside on specific plasmid groups. Future surveillance should monitor these high-risk plasmid groups for potential gene acquisition and spread.
Area of Science:
- Genetics
- Microbiology
- Epidemiology
Background:
- Plasmids are key vectors for antimicrobial resistance genes (ARGs) and other clinically significant traits.
- Previous research on complete plasmid assemblies is limited in scale and scope, often focusing only on ARGs.
Purpose of the Study:
- To characterize a large collection of complete plasmids from bloodstream infections.
- To understand the distribution and gene content of plasmids, particularly those carrying ARGs.
- To identify plasmid features that predict ARG carriage and potential for dissemination.
Main Methods:
- Sequencing of 1,880 complete plasmids from 738 bacterial isolates from UK bloodstream infections (2009, 2018, and intervening years).
- Analysis of plasmid host range, gene repertoire overlap between species, and association of ARGs with specific plasmid groups.
- Investigation of shared genetic elements ('backbone') between plasmids with and without ARGs.
Main Results:
- Plasmids are predominantly host-species-specific but show significant gene-repertoire overlap.
- Most ARGs are found on a limited number of plasmid groups with predictable biological features.
- Plasmids carrying ARGs, including carbapenemases, share core genes with non-ARG plasmids.
Conclusions:
- Plasmids play a crucial role in the dissemination of antimicrobial resistance.
- Identifying and monitoring high-risk plasmid groups is essential for effective surveillance.
- Future strategies should focus on plasmids with the potential to acquire and spread clinically important genes.
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