title: HicA toxin of Escherichia coli derepresses hicAB transcription to selectively produce HicB antitoxin.
abstract: Antitoxins encoded by type II toxin - antitoxin (TA) modules neutralize cognate toxins by direct protein - protein contact and in addition, regulate TA operon transcription by binding to operators in the promoter regions. On top of the simple negative feed-back regulation, canonical type II TA operons are regulated by a mechanism called 'Conditional Cooperativity'(CC). In CC, the cellular toxin:antitoxin (T:A) ratio controls the transcription-rate such that low T:A ratios favour repression and high T:A ratios favour de-repression of TA operon transcription. Here a new molecular mechanism that secures selective synthesis of antitoxin in the presence of excess toxin was unravelled. The hicAB locus of E. coli K-12 encodes HicA mRNase and HicB antitoxin. It was shown that hicAB is transcribed by two promoters, an upstream one that is activated by CRP-cAMP and competence factor Sxy and a downstream one that is autorepressed solely by HicB. Excess HicA destabilizes the HicB•operator complex in vitro and consistently, activates hicAB transcription in vivo. Remarkably, the hicAB transcript synthesized from the HicB-controlled promoter produces HicB but not HicA. Thus, the HicA-mediated derepression of hicAB transcription provides a mechanism that conditionally and selectively stimulates synthesis of HicB antitoxin under conditions of excess HicA toxin.
authors.affiliation: Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, Copenhagen, DK-2200, Denmark.
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Turnbull
authors.affiliation: Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, Copenhagen, DK-2200, Denmark.
authors.forename: Kenn
authors.identifier: http://orcid.org/0000-0002-7462-4612
authors.initials: K
authors.lastname: Gerdes
mesh_terms: D000992:Antitoxins / Q000096:biosynthesis* / Q000235:genetics; D001427:Bacterial Toxins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D048168:Escherichia coli K12 / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D009876:Operon; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
chemical_list: D000992:Antitoxins; D001427:Bacterial Toxins; D029968:Escherichia coli Proteins