title: Toxin-antitoxin modules as bacterial metabolic stress managers.
abstract: Bacterial genomes frequently contain operons that encode a toxin and its antidote. These 'toxin-antitoxin (TA) modules' have an important role in bacterial stress physiology and might form the basis of multidrug resistance. The toxins in TA modules act as gyrase poisons or stall the ribosome by mediating the cleavage of mRNA. The antidotes contain an N-terminal DNA-binding region of variable fold and a C-terminal toxin-inhibiting domain. When bound to toxin, the C-terminal domain adopts an extended conformation. In the absence of toxin, by contrast, this domain (and sometimes the whole antidote protein) remains unstructured, allowing its fast degradation by proteolysis. Under silent conditions the antidote inhibits the toxin and the toxin-antidote complex acts as a repressor for the TA operon, whereas under conditions of activation proteolytic degradation of the antidote outpaces its synthesis.
authors.affiliation: Laboratorium voor Ultrastructuur, Vrije Universiteit Brussel, and Department of Molecular and Cellular Interactions, Vlaams Interuniversitair Instituut voor Biotechnologie, Pleinlaan 2, B-1050 Brussel, Belgium.
authors.forename: Lieven
authors.initials: L
authors.lastname: Buts
authors.forename: Jurij
authors.initials: J
authors.lastname: Lah
authors.forename: Minh-Hoa
authors.initials: MH
authors.lastname: Dao-Thi
authors.forename: Lode
authors.initials: L
authors.lastname: Wyns
authors.forename: Remy
authors.initials: R
authors.lastname: Loris
mesh_terms: D000992:Antitoxins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001419:Bacteria / Q000235:genetics / Q000378:metabolism; D001427:Bacterial Toxins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D027081:DNA Gyrase / Q000378:metabolism; D004269:DNA, Bacterial / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D008954:Models, Biological; D008958:Models, Molecular; D046912:Multiprotein Complexes; D017510:Protein Folding; D012329:RNA, Bacterial / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D000992:Antitoxins; D001427:Bacterial Toxins; D004269:DNA, Bacterial; D046912:Multiprotein Complexes; D012329:RNA, Bacterial; D012333:RNA, Messenger; D027081:DNA Gyrase