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Factors associated with plasmid antibiotic resistance gene carriage revealed using large-scale multivariable analysis

Abstract:
Plasmids are major vectors of bacterial antibiotic resistance, but understanding of factors associated with plasmid antibiotic resistance gene (ARG) carriage is limited. We curated > 14,000 publicly available plasmid genomes and associated metadata. Duplicate and replicate plasmids were excluded; where possible, sample metadata was validated externally (BacDive database). Using Generalised Additive Models (GAMs) we assessed the influence of 12 biotic/abiotic factors (e.g. plasmid genetic factors, isolation source, collection date) on ARG carriage, modelled as a binary outcome. Separate GAMs were built for 10 major ARG types. Multivariable analysis indicated that plasmid ARG carriage patterns across time (collection years), isolation sources (human/livestock) and host bacterial taxa were consistent with antibiotic selection pressure as a driver of plasmid-mediated antibiotic resistance. Only 0.42% livestock plasmids carried carbapenem resistance (compared with 12% human plasmids); conversely, tetracycline resistance was enriched in livestock vs human plasmids, reflecting known prescribing practices. Interpreting results using a timeline of ARG type acquisition (determined by literature review) yielded additional novel insights. More recently acquired ARG types (e.g. colistin and carbapenem) showed increases in plasmid carriage during the date range analysed (1994–2019), potentially reflecting recent onset of selection pressure; they also co-occurred less commonly with ARGs of other types, and virulence genes. Overall, this suggests that following acquisition, plasmid ARGs tend to accumulate under antibiotic selection pressure and co-associate with other adaptive genes (other ARG types, virulence genes), potentially re-enforcing plasmid ARG carriage through co-selection.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/s41598-023-29530-y

Authors


More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Research group:
NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Research group:
NIHR Oxford Biomedical Research Centre
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
NDM Experimental Medicine
Research group:
NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance; NIHR Oxford Biomedical Research Centre
Role:
Author
ORCID:
0000-0002-0412-8509


Publisher:
Springer Nature
Journal:
Scientific Reports More from this journal
Volume:
13
Issue:
1
Article number:
2500
Publication date:
2023-02-13
Acceptance date:
2023-02-06
DOI:
EISSN:
2045-2322


Language:
English
Keywords:
Subjects:
Pubs id:
1327840
Local pid:
pubs:1327840
Deposit date:
2023-02-08

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