title: How antibiotics kill bacteria: from targets to networks.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute and the Department of Biomedical Engineering, Center for BioDynamics and Center for Advanced Biotechnology, Boston University, 44 Cummington Street, Boston, Massachusetts 02215, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Kohanski
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Dwyer
authors.forename: James J
authors.initials: JJ
authors.lastname: Collins
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D002473:Cell Wall / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D055808:Drug Discovery; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis; D012294:Rifamycins / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D019384:Nucleic Acid Synthesis Inhibitors; D015363:Quinolones; D012294:Rifamycins; D012313:RNA