title: Toxin-antitoxin systems in bacterial growth arrest and persistence.
abstract: Bacterial persister cells constitute a subpopulation of genetically identical, metabolically slow-growing cells that are highly tolerant of antibiotics and other environmental stresses. Recent studies have demonstrated that gene loci known as toxin-antitoxin (TA) modules play a central role in the persister state. Under normal growth conditions, antitoxins potently inhibit the activities of the toxins. In contrast, under conditions of stress, the antitoxins are selectively degraded, freeing the toxins to inhibit essential cellular processes, such as DNA replication and protein translation. This inhibition results in rapid growth arrest. In this Review, we highlight recent discoveries of these multifaceted TA systems with a focus on the newly uncovered mechanisms, especially conditional cooperativity, that are used to regulate cell growth and persistence. We also discuss the potential for targeting TA systems for antimicrobial drug discovery.
authors.affiliation: Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, Rhode Island, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Page
authors.affiliation: Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, Rhode Island, USA.|Department of Chemistry, Brown University, Providence, Rhode Island, USA.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Peti
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000992:Antitoxins / Q000235:genetics*; D001427:Bacterial Toxins / Q000235:genetics*; D055808:Drug Discovery; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D008954:Models, Biological; D009154:Mutation
chemical_list: D000900:Anti-Bacterial Agents; D000992:Antitoxins; D001427:Bacterial Toxins