Plasmid prevalence is independent of antibiotic resistance in environmental Enterobacteriaceae

The rapid rise of antibiotic-resistant pathogens poses a critical threat to the treatment of infectious diseases. While the spread of antibiotic resistance genes (ARGs) via plasmid conjugation has been extensively studied both in the lab and the clinic, the prevalence and diversity of plasmids in drug-susceptible isolates (e.g. isolates that do not contain ARGs) remain poorly understood. Yet, plasmids in susceptible isolates play a pivotal role as reservoirs, potentially capturing and disseminating ARGs <i>in situ</i>. To better understand the potential impact of these strains, we investigated the prevalence and characteristics of plasmids in >200 <i>Enterobacteriaceae</i>, including those that are primarily drug susceptible, isolated from diverse environmental sources. Using whole-genome sequencing and a novel bioinformatic pipeline, we quantified the number of large plasmids per isolate and examined the relationship between plasmid abundance and host antibiotic susceptibility profiles. Strikingly, we found a high abundance of plasmids in susceptible strains, with no correlation between plasmid number and susceptibility level to a variety of clinically relevant antibiotics. Moreover, plasmid abundance did not influence a strain's ability to accept additional plasmids via conjugation. These findings reveal that plasmids are widespread in susceptible strains regardless of ARG content and underscore their potential to act as conduits for future resistance dissemination.