title: Mechanistic insights into type I toxin antitoxin systems in Helicobacter pylori: the importance of mRNA folding in controlling toxin expression.
abstract: Type I toxin-antitoxin (TA) systems have been identified in a wide range of bacterial genomes. Here, we report the characterization of a new type I TA system present on the chromosome of the major human gastric pathogen, Helicobacter pylori. We show that the aapA1 gene encodes a 30 amino acid peptide whose artificial expression in H. pylori induces cell death. The synthesis of this toxin is prevented by the transcription of an antitoxin RNA, named IsoA1, expressed on the opposite strand of the toxin gene. We further reveal additional layers of post-transcriptional regulation that control toxin expression: (i) transcription of the aapA1 gene generates a full-length transcript whose folding impedes translation (ii) a 3΄ end processing of this message generates a shorter transcript that, after a structural rearrangement, becomes translatable (iii) but this rearrangement also leads to the formation of two stem-loop structures allowing formation of an extended duplex with IsoA1 via kissing-loop interactions. This interaction ensures both the translation inhibition of the AapA1 active message and its rapid degradation by RNase III, thus preventing toxin synthesis under normal growth conditions. Finally, a search for homologous mRNA structures identifies similar TA systems in a large number of Helicobacter and Campylobacter genomes.
authors.affiliation: INSERM U1212, CNRS UMR5320, Univ. Bordeaux, ARNA Laboratory, 146 rue Léo Saignat, F-33076 Bordeaux, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Arnion
authors.affiliation: INSERM U1212, CNRS UMR5320, Univ. Bordeaux, ARNA Laboratory, 146 rue Léo Saignat, F-33076 Bordeaux, France.
authors.forename: Dursun Nizam
authors.initials: DN
authors.lastname: Korkut
authors.affiliation: INSERM U1212, CNRS UMR5320, Univ. Bordeaux, ARNA Laboratory, 146 rue Léo Saignat, F-33076 Bordeaux, France.
authors.forename: Sara
authors.initials: S
authors.lastname: Masachis Gelo
authors.affiliation: INSERM U1212, CNRS UMR5320, Univ. Bordeaux, ARNA Laboratory, 146 rue Léo Saignat, F-33076 Bordeaux, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Chabas
authors.affiliation: INSERM U1212, CNRS UMR5320, Univ. Bordeaux, ARNA Laboratory, 146 rue Léo Saignat, F-33076 Bordeaux, France.
authors.forename: Jérémy
authors.initials: J
authors.lastname: Reignier
authors.affiliation: INSERM U1212, CNRS UMR5320, Univ. Bordeaux, ARNA Laboratory, 146 rue Léo Saignat, F-33076 Bordeaux, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Iost
authors.affiliation: INSERM U1212, CNRS UMR5320, Univ. Bordeaux, ARNA Laboratory, 146 rue Léo Saignat, F-33076 Bordeaux, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Darfeuille
mesh_terms: D000992:Antitoxins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics*; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D004926:Escherichia coli; D015964:Gene Expression Regulation, Bacterial; D016680:Genome, Bacterial; D016480:Helicobacter pylori / Q000737:chemistry / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D059370:RNA Folding / Q000235:genetics*; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics; D012329:RNA, Bacterial / Q000235:genetics*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000737:chemistry; D043244:Ribonuclease III / Q000737:chemistry / Q000235:genetics
chemical_list: C000622449:AapA1 protein, Helicobacter pylori; D000992:Antitoxins; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D012329:RNA, Bacterial; D012333:RNA, Messenger; D043244:Ribonuclease III