Insufficient development of new antibiotics and the rising resistance of bacteria to those that we have are putting the world at risk of losing the most widely curative class of medicines currently available. Preventing deaths from antimicrobial resistance (AMR) will require exploiting emerging knowledge not only about genetic AMR conferred by horizontal gene transfer or de novo mutations but also about phenotypic AMR, which lacks a stably heritable basis. This Review summarizes recent advances and continuing limitations in our understanding of AMR and suggests approaches for combating its clinical consequences, including identification of previously unexploited bacterial targets, new antimicrobial compounds, and improved combination drug regimens.
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