title: Regulating toxin-antitoxin expression: controlled detonation of intracellular molecular timebombs.
abstract: Genes for toxin-antitoxin (TA) complexes are widely disseminated in bacteria, including in pathogenic and antibiotic resistant species. The toxins are liberated from association with the cognate antitoxins by certain physiological triggers to impair vital cellular functions. TAs also are implicated in antibiotic persistence, biofilm formation, and bacteriophage resistance. Among the ever increasing number of TA modules that have been identified, the most numerous are complexes in which both toxin and antitoxin are proteins. Transcriptional autoregulation of the operons encoding these complexes is key to ensuring balanced TA production and to prevent inadvertent toxin release. Control typically is exerted by binding of the antitoxin to regulatory sequences upstream of the operons. The toxin protein commonly works as a transcriptional corepressor that remodels and stabilizes the antitoxin. However, there are notable exceptions to this paradigm. Moreover, it is becoming clear that TA complexes often form one strand in an interconnected web of stress responses suggesting that their transcriptional regulation may prove to be more intricate than currently understood. Furthermore, interference with TA gene transcriptional autoregulation holds considerable promise as a novel antibacterial strategy: artificial release of the toxin factor using designer drugs is a potential approach to induce bacterial suicide from within.
authors.affiliation: Faculty of Life Sciences and Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester M1 7DN, UK. finbarr.hayes@manchester.ac.uk.
authors.forename: Finbarr
authors.initials: F
authors.lastname: Hayes
authors.affiliation: Faculty of Life Sciences and Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester M1 7DN, UK. barbara.kedzierska@biol.ug.edu.pl.
authors.forename: Barbara
authors.initials: B
authors.lastname: Kędzierska
mesh_terms: D000992:Antitoxins / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D027081:DNA Gyrase / Q000235:genetics / Q000378:metabolism; D004269:DNA, Bacterial / Q000235:genetics; D063185:Epigenetic Repression; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D014118:Toxins, Biological / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D000992:Antitoxins; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D014118:Toxins, Biological; D027081:DNA Gyrase