How antibiotics kill bacteria: from targets to networks

Bacterial responses to antibiotics are complex and involve many genetic and biochemical pathways. This Review describes the effects of bactericidal antibiotics on bacterial cellular processes, the associated responses that contribute to killing and recent insights into these processes revealed through the study of biological networks. Antibiotic drug–target interactions, and their respective direct effects, are generally well characterized. By contrast, the bacterial responses to antibiotic drug treatments that contribute to cell death are not as well understood and have proven to be complex as they involve many genetic and biochemical pathways. In this Review, we discuss the multilayered effects of drug–target interactions, including the essential cellular processes that are inhibited by bactericidal antibiotics and the associated cellular response mechanisms that contribute to killing. We also discuss new insights into these mechanisms that have been revealed through the study of biological networks, and describe how these insights, together with related developments in synthetic biology, could be exploited to create new antibacterial therapies.