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

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.