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.

Details

Title
Factors associated with plasmid antibiotic resistance gene carriage revealed using large-scale multivariable analysis
Author
Orlek, Alex 1 ; Anjum, Muna F. 2 ; Mather, Alison E. 3 ; Stoesser, Nicole 4 ; Walker, A. Sarah 5 

 UK Health Security Agency, HCAI, Fungal, AMR, AMU & Sepsis Division, London, UK (GRID:grid.515304.6) (ISNI:0000 0005 0421 4601); University of Oxford, Nuffield Department of Medicine, Oxford, UK (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948); University of Oxford, NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Oxford, UK (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948) 
 Animal and Plant Health Agency, Department of Bacteriology, Weybridge, Addlestone, UK (GRID:grid.422685.f) (ISNI:0000 0004 1765 422X) 
 Quadram Institute Bioscience, Norwich, UK (GRID:grid.40368.39) (ISNI:0000 0000 9347 0159); University of East Anglia, Norwich, UK (GRID:grid.8273.e) (ISNI:0000 0001 1092 7967) 
 University of Oxford, Nuffield Department of Medicine, Oxford, UK (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948); University of Oxford, NIHR Oxford Biomedical Research Centre (BRC), Oxford, UK (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948) 
 University of Oxford, Nuffield Department of Medicine, Oxford, UK (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948); University of Oxford, NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Oxford, UK (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948); University of Oxford, NIHR Oxford Biomedical Research Centre (BRC), Oxford, UK (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948) 
Pages
2500
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2775877193
Copyright
© Crown 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.