Host-specific plasmid evolution explains the variable spread of clinical antibiotic-resistance plasmids

Abstract

Antibiotic resistance encoded on plasmids is a pressing global health problem. Predicting which plasmids spread/decline in the long term remains a huge challenge, even though some key parameters influencing plasmid stability have been identified, such as plasmid growth costs and horizontal transfer rates. Here, we show these parameters evolve in a strain-specific way among clinical plasmids/bacteria, and this occurs rapidly enough to alter the relative likelihoods of different bacterium-plasmid combinations spreading/declining. We used experiments with Escherichia coli and antibiotic-resistance plasmids isolated from patients, paired with a mathematical model, to show long-term plasmid stability (beyond antibiotic exposure) was better explained by evolutionary changes in plasmid-stability traits than by initial variation among bacterium-plasmid combinations. Evolutionary trajectories were specific to particular bacterium-plasmid combinations. Genome sequencing and genetic manipulation helped explain this, revealing epistatic (here, strain-dependent) effects of key genetic changes affecting horizontal plasmid transfer. Several genetic changes involved mobile elements and pathogenicity islands. Rapid strain-specific evolution can thus outweigh ancestral phenotypes as a predictor of plasmid stability. Accounting for strain-specific plasmid evolution in natural populations could improve our ability to anticipate and manage successful bacterium-plasmid combinations.

Evolutionary Responses to Acquiring a Multidrug Resistance Plasmid Are Dominated by Metabolic Functions across Diverse Escherichia coli Lineages

“…Alternatively, these evolutionary responses can be more extensive, involving coadaptation of the chromosome and plasmid, whereby multiple mutations occurring on both replicons are necessary to assimilate the plasmid into the genome ( 17 – 19 ). To date, few studies have compared the evolutionary responses of diverse lineages to acquiring a new plasmid at the genomic level ( 16 , 19 , 20 ). As such little is known about how the evolutionary processes of genomic integration of an MDR plasmid vary between genomically diverse bacterial lineages.…”

Real-time visualisation of the intracellular dynamics of conjugative plasmid transfer

“…In addition, the leading regions of plasmids belonging to a wide range of incompatibility groups (IncF, IncN, IncP9 and IncW) classified as MOBF plasmids using the relaxase as a phylogenetic marker were reported to be the preferential target for CRISPR-Cas systems directed against conjugation 8,91,92 . Recently, the leading region was shown to be an important evolutionary target for the dissemination of the pESBL (IncI) plasmid 93 . Concerning the F plasmid, we can stress that Frpo1 and Frpo2 share 92% similarity at the nucleotide level and are located only about 5 kb apart.…”

Real time visualisation of conjugation reveals the molecular strategy evolved by the conjugative F plasmid to ensure the sequential production of plasmid factors during establishment in the new host cell

“…In addition, the leading regions of plasmids belonging to a wide range of incompatibility groups (IncF, IncN, IncP9 and IncW) classified as MOBF plasmids using the relaxase as a phylogenetic marker were reported to be the preferential target for CRISPR-Cas systems directed against conjugation (Fernandez-Lopez et al, 2016; Garcillán-Barcia et al, 2009; Westra et al, 2013). Recently, the leading region was shown to be an important evolutionary target for the dissemination of the pESLB (IncI) plasmid (Benz and Hall, 2022). Concerning the F plasmid, we can stress that F rpo1 and F rpo2 share 92 % similarity at the nucleotide level and are located only about 5 kb apart.…”