title: Growth control switch by a DNA-damage-inducible toxin-antitoxin system in Caulobacter crescentus.
abstract: Bacterial toxin-antitoxin systems (TASs) are thought to respond to various stresses, often inducing growth-arrested (persistent) sub-populations of cells whose housekeeping functions are inhibited. Many such TASs induce this effect through the translation-dependent RNA cleavage (RNase) activity of their toxins, which are held in check by their cognate antitoxins in the absence of stress. However, it is not always clear whether specific mRNA targets of orthologous RNase toxins are responsible for their phenotypic effect, which has made it difficult to accurately place the multitude of TASs within cellular and adaptive regulatory networks. Here, we show that the TAS HigBA of Caulobacter crescentus can promote and inhibit bacterial growth dependent on the dosage of HigB, a toxin regulated by the DNA damage (SOS) repressor LexA in addition to its antitoxin HigA, and the target selectivity of HigB's mRNA cleavage activity. HigB reduced the expression of an efflux pump that is toxic to a polarity control mutant, cripples the growth of cells lacking LexA, and targets the cell cycle circuitry. Thus, TASs can have outcome switching activity in bacterial adaptive (stress) and systemic (cell cycle) networks.
authors: Department of Microbiology &Molecular Medicine, Institute of Genetics &Genomics in Geneva (iGE3), Faculty of Medicine/CMU, University of Geneva, Rue Michel-Servet 1, 1211 Genève 4, Switzerland.
authors: Clare L
authors: CL
authors: Kirkpatrick
authors: Department of Microbiology &Molecular Medicine, Institute of Genetics &Genomics in Geneva (iGE3), Faculty of Medicine/CMU, University of Geneva, Rue Michel-Servet 1, 1211 Genève 4, Switzerland.
authors: Daniel
authors: D
authors: Martins
authors: Department of Microbiology &Molecular Medicine, Institute of Genetics &Genomics in Geneva (iGE3), Faculty of Medicine/CMU, University of Geneva, Rue Michel-Servet 1, 1211 Genève 4, Switzerland.
authors: Peter
authors: P
authors: Redder
authors: Department of Microbiology &Molecular Medicine, Institute of Genetics &Genomics in Geneva (iGE3), Faculty of Medicine/CMU, University of Geneva, Rue Michel-Servet 1, 1211 Genève 4, Switzerland.
authors: Antonio
authors: A
authors: Frandi
authors: Department of Microbiology &Molecular Medicine, Institute of Genetics &Genomics in Geneva (iGE3), Faculty of Medicine/CMU, University of Geneva, Rue Michel-Servet 1, 1211 Genève 4, Switzerland.
authors: Johann
authors: J
authors: Mignolet
authors: Biomolecular Screening Facility, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors: Julien Bortoli
authors: JB
authors: Chapalay
authors: Biomolecular Screening Facility, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors: Marc
authors: M
authors: Chambon
authors: Biomolecular Screening Facility, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors: Gerardo
authors: G
authors: Turcatti
authors: Department of Microbiology &Molecular Medicine, Institute of Genetics &Genomics in Geneva (iGE3), Faculty of Medicine/CMU, University of Geneva, Rue Michel-Servet 1, 1211 Genève 4, Switzerland.
authors: Patrick H
authors: PH
authors: Viollier
mesh_terms: D000222:Adaptation, Physiological; D001426:Bacterial Proteins / Q000378:metabolism*; D016935:Caulobacter crescentus / Q000235:genetics* / Q000254:growth & development*; D004249:DNA Damage; D015964:Gene Expression Regulation, Bacterial; D012697:Serine Endopeptidases / Q000378:metabolism*; D000075704:Toxin-Antitoxin Systems; D000099160:LexA Repressor Protein
chemical_list: D001426:Bacterial Proteins; D012697:Serine Endopeptidases; D000099160:LexA Repressor Protein