Piggybacking on Niche Adaptation Improves the Maintenance of Multidrug-Resistance Plasmids

Abstract The persistence of plasmids in bacterial populations represents a puzzling evolutionary problem with serious clinical implications due to their role the ongoing antibiotic resistance crisis. Recently, major advancements have been made toward resolving this “plasmid paradox” but mainly nonclinical context. Here, we propose an additional explanation for maintenance multidrug-resistance Escherichia coli strains. After coevolving two encoding last resort carbapenems extraintestinal pathogenic E. strain, observed that chromosomal media adaptive mutations global regulatory systems CCR (carbon catabolite repression) and ArcAB (aerobic respiration control) pleiotropically improved both plasmids. Mechanistically, net downregulation plasmid gene expression reduced fitness cost. Our results suggest transcriptional rewiring during niche adaptation may facilitate maintenance.