Resistance potentiators: Evolutionary catalysts of antibiotic resistance.

Why do even closely-related bacteria differ in their capacity to evolve antibiotic resistance? Drawing on evidence from experimental evolution, pathogen genomics, and molecular microbiology, this Essay argues that the evolution of antibiotic resistance in bacterial genomes is frequently catalyzed by the presence of 'resistance potentiators': genes, elements, or pathways that accelerate evolution in a trait-specific manner. Epidemiological evidence suggests that resistance potentiators that modulate phenotypes have been particularly important in successful pathogen lineages. Furthermore, experimental models show that combining antibiotics with inhibitors of resistance potentiators can restrict the evolution of resistance, suggesting that they could be future drug targets or otherwise lead to more evolution-informed antibiotic therapy.