| الوصف: |
Plasmids are key vectors of bacterial antibiotic resistance, but understanding of risk factors associated with plasmid antibiotic resistance gene (ARG) carriage is limited. We curated >14000 publicly available plasmid genomes and associated metadata. Duplicate and replicate plasmids were excluded; where possible, sample metadata was validated externally (BacDive database). Using Logistic Generalised Additive Models (GAMs) we assessed the influence of biotic/abiotic risk 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. Among livestock vs human plasmids, carbapenem resistance was infrequent (0.42% vs 12%), while tetracycline resistance was enriched (adjusted odds-ratio [OR]=2.65, 95% confidence interval [CI] 1.89–3.72), reflecting known prescribing practices. 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. Carbapenem resistance was more likely to reside on conjugative vs non-mobilisable plasmids (adjusted OR=3.59 95%CI 2.80–4.61), and on plasmids with a higher density of insertion sequences. 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. |
