title: Two regulatory RNA elements affect TisB-dependent depolarization and persister formation.
abstract: Bacterial survival strategies involve phenotypic diversity which is generated by regulatory factors and noisy expression of effector proteins. The question of how bacteria exploit regulatory RNAs to make decisions between phenotypes is central to a general understanding of these universal regulators. We investigated the TisB/IstR-1 toxin-antitoxin system of Escherichia coli to appreciate the role of the RNA antitoxin IstR-1 in TisB-dependent depolarization of the inner membrane and persister formation. Persisters are phenotypic variants that have become transiently drug-tolerant by arresting growth. The RNA antitoxin IstR-1 sets a threshold for TisB-dependent depolarization under DNA-damaging conditions, resulting in two sub-populations: polarized and depolarized cells. Furthermore, our data indicate that an inhibitory 5' UTR structure in the tisB mRNA serves as a regulatory RNA element that delays TisB translation to avoid inappropriate depolarization when DNA damage is low. Investigation of the persister sub-population further revealed that both regulatory RNA elements affect persister levels as well as persistence time. This work provides an intriguing example of how bacteria exploit regulatory RNAs to control phenotypic heterogeneity.
authors.affiliation: Department of Cell and Molecular Biology, Uppsala University, Uppsala, 75124, Sweden.
authors.forename: Bork A
authors.initials: BA
authors.lastname: Berghoff
authors.affiliation: Department of Cell and Molecular Biology, Uppsala University, Uppsala, 75124, Sweden.
authors.forename: Mirthe
authors.initials: M
authors.lastname: Hoekzema
authors.affiliation: Department of Cell and Molecular Biology, Uppsala University, Uppsala, 75124, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Aulbach
authors.affiliation: Department of Cell and Molecular Biology, Uppsala University, Uppsala, 75124, Sweden.
authors.forename: E Gerhart H
authors.initials: EG
authors.lastname: Wagner
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001427:Bacterial Toxins / Q000235:genetics*; D002462:Cell Membrane / Q000473:pathology; D002939:Ciprofloxacin / Q000494:pharmacology*; D004249:DNA Damage / Q000235:genetics*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics*; D014176:Protein Biosynthesis / Q000235:genetics*; D012329:RNA, Bacterial / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D058727:RNA, Small Untranslated / Q000235:genetics*; D038621:Regulatory Sequences, Ribonucleic Acid / Q000235:genetics*; D013014:SOS Response, Genetics / Q000187:drug effects / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D029968:Escherichia coli Proteins; D012329:RNA, Bacterial; D012333:RNA, Messenger; D058727:RNA, Small Untranslated; D038621:Regulatory Sequences, Ribonucleic Acid; C575529:TisB toxin, E coli; D002939:Ciprofloxacin