Molecular mechanisms of antibiotic resistance revisited

Antibiotic resistance is a global health emergency, with resistance detected to all antibiotics currently in clinical use and only a few novel drugs in the pipeline. Understanding the molecular mechanisms that bacteria use to resist the action of antimicrobials is critical to recognize global patterns of resistance and to improve the use of current drugs, as well as for the design of new drugs less susceptible to resistance development and novel strategies to combat resistance. In this Review, we explore recent advances in understanding how resistance genes contribute to the biology of the host, new structural details of relevant molecular events underpinning resistance, the identification of new resistance gene families and the interactions between different resistance mechanisms. Finally, we discuss how we can use this information to develop the next generation of antimicrobial therapies. In this Review, Blair, Webber and colleagues explore our understanding of the mechanisms of antibiotic resistance, including reduced permeability, antibiotic efflux, modification or alteration of the antibiotic target, modification or destruction of the drug itself, and bypass of metabolic pathways. They also discuss how this information can aid in developing the next generation of antimicrobial therapies.