Collateral sensitivity and genetic vulnerability of antibiotic resistance.

Antibiotic combination therapy has a critical role in limiting emergent antibiotic resistance in bacterial pathogens. Collateral sensitivity (CS), resistance to one antibiotic that is inextricable from sensitivity to another antibiotic, presents an opportunity for combinations explicitly selecting against resistance. Complementing efforts to select against resistance, differential genetic vulnerability mapping unravels dependencies unique for resistant strains. In this review, we discuss the potential implications of CS and genetic vulnerability data for the design of bespoke antibiotic combinations, drug discovery, and tracking evolution of resistant strains.