Competition between plasmids conferring the same antimicrobial resistance leads to plasmid-host network specialisation

Plasmids have a key role in disseminating antimicrobial resistance (AMR). Previous work has shown that in the presence of antibiotics, plasmids conferring AMR will spread to a larger number and a more phylogenetically diverse group of host organisms. However, this pattern may be complicated when multiple plasmids confer the same resistance. Here, we analyse host-plasmid networks in experimental communities of three bacterial species cultured for six weeks with three incompatible plasmids (plasmids that cannot stably coexist within a single cell) conferring tetracycline resistance. The communities are cultured either without tetracycline, or with a low or high dose of the antibiotic. We find that while antibiotic selection leads to higher plasmid prevalence, it does not change the structure of host-plasmid networks. Under all conditions, the networks become highly specialised, as specific host-plasmid pairings emerge. This result is supported by a previously published mathematical model parameterised to match our experimental set-up. Our study reiterates the importance of fitness effects of plasmids in determining the structure of bacteria-plasmid networks. The spread of a given AMR plasmid is reduced when fitness differences are reduced due to other plasmids carrying AMR genes, leading to more specialised bacteria-plasmid networks.