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

Orlek, Alex, Anjum, Muna F., Mather, Alison E., Stoesser, Nicole and Walker, A. Sarah (2023) Factors associated with plasmid antibiotic resistance gene carriage revealed using large-scale multivariable analysis. Scientific Reports, 13. ISSN 2045-2322

[thumbnail of Orlek_etal_2023_SciRep]
PDF (Orlek_etal_2023_SciRep) - Published Version
Available under License Creative Commons Attribution.

Download (2MB) | Preview


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.

Item Type: Article
Additional Information: Data availability: Curated plasmid sequences (14,143 plasmids) are available as a FASTA file (https://doi.org/10.6084/m9.figshare.19438994). Supplementary Data 1 provides the tabular plasmid dataset used for statistical analysis (including plasmid accession numbers) (https://github.com/AlexOrlek/PlasmidAMRCarriage_paper/blob/main/data/Data_S1.xlsx). Code for statistical analysis is available: https://github.com/AlexOrlek/PlasmidARGCarriage. Funding information: This study was funded by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Healthcare Associated Infections and Antimicrobial Resistance at Oxford University in partnership with Public Health England (PHE) (NIHR200915), and was supported by the NIHR Biomedical Research Centre, Oxford. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, the Department of Health and Social Care, or UK Health Security Agency. ASW is an NIHR Senior Investigator. AEM is supported by the Biotechnology and Biological Sciences Research Council (BBSRC) Institute Strategic Programme Microbes in the Food Chain BB/R012504/1 and its constituent project BBS/E/F/000PR10348 (Theme 1, Epidemiology and Evolution of Pathogens in the Food Chain).
Faculty \ School:
Faculty of Medicine and Health Sciences > Norwich Medical School
Related URLs:
Depositing User: LivePure Connector
Date Deposited: 03 Aug 2023 15:33
Last Modified: 10 Aug 2023 08:31
URI: https://ueaeprints.uea.ac.uk/id/eprint/92769
DOI: 10.1038/s41598-023-29530-y


Downloads per month over past year

Actions (login required)

View Item View Item