title: The ζ toxin induces a set of protective responses and dormancy.
abstract: The ζε module consists of a labile antitoxin protein, ε, which in dimer form (ε(2)) interferes with the action of the long-living monomeric ζ phosphotransferase toxin through protein complex formation. Toxin ζ, which inhibits cell wall biosynthesis and may be bactericide in nature, at or near physiological concentrations induces reversible cessation of Bacillus subtilis proliferation (protective dormancy) by targeting essential metabolic functions followed by propidium iodide (PI) staining in a fraction (20-30%) of the population and selects a subpopulation of cells that exhibit non-inheritable tolerance (1-5×10(-5)). Early after induction ζ toxin alters the expression of ∼78 genes, with the up-regulation of relA among them. RelA contributes to enforce toxin-induced dormancy. At later times, free active ζ decreases synthesis of macromolecules and releases intracellular K(+). We propose that ζ toxin induces reversible protective dormancy and permeation to PI, and expression of ε(2) antitoxin reverses these effects. At later times, toxin expression is followed by death of a small fraction (∼10%) of PI stained cells that exited earlier or did not enter into the dormant state. Recovery from stress leads to de novo synthesis of ε(2) antitoxin, which blocks ATP binding by ζ toxin, thereby inhibiting its phosphotransferase activity.
authors.affiliation: Department of Microbial Biotechnology, Centro Nacional de Biotecnología, (CNB-CSIC), Madrid, Spain.
authors.forename: Virginia S
authors.initials: VS
authors.lastname: Lioy
authors.forename: Cristina
authors.initials: C
authors.lastname: Machon
authors.forename: Mariangela
authors.initials: M
authors.lastname: Tabone
authors.forename: José E
authors.initials: JE
authors.lastname: Gonzalez-Pastor
authors.forename: Rimantas
authors.initials: R
authors.lastname: Daugelavicius
authors.forename: Silvia
authors.initials: S
authors.lastname: Ayora
authors.forename: Juan C
authors.initials: JC
authors.lastname: Alonso
mesh_terms: D001412:Bacillus subtilis / Q000166:cytology* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D016923:Cell Death; D002462:Cell Membrane / Q000378:metabolism; D002463:Cell Membrane Permeability; D049109:Cell Proliferation; D011756:Diphosphates / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006160:Guanosine Triphosphate / Q000378:metabolism; D042541:Intracellular Space / Q000378:metabolism; D011419:Propidium / Q000378:metabolism; D014118:Toxins, Biological / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D011756:Diphosphates; D014118:Toxins, Biological; D011419:Propidium; D006160:Guanosine Triphosphate