The ζ toxin induces a set of protective responses and dormancy

• Published in: PloS one Vol. 7; no. 1; p. e30282
• Main Authors: Lioy, Virginia S, Machon, Cristina, Tabone, Mariangela, Gonzalez-Pastor, José E, Daugelavicius, Rimantas, Ayora, Silvia, Alonso, Juan C
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 25-01-2012; Public Library of Science (PLoS)
• Subjects: Antibiotics; Apoptosis; Bacillus subtilis; Bacillus subtilis - cytology; Bacillus subtilis - genetics; Bacillus subtilis - growth & development; Bacillus subtilis - metabolism; Bacteria; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bactericides; Biology; Biosynthesis; Biotechnology; Cell Death; Cell division; Cell growth; Cell Membrane - metabolism; Cell Membrane Permeability; Cell Proliferation; Cell walls; Complex formation; Deoxyribonucleic acid; Diphosphates - metabolism; DNA; Dormancy; Escherichia coli; Firmicutes; Gene expression; Gene Expression Regulation, Bacterial; Gene regulation; Genomics; Guanosine Triphosphate - metabolism; Intracellular Space - metabolism; Iodides; Macromolecules; Phosphotransferase; Physiology; Propidium - metabolism; Propidium iodide; Protein synthesis; Proteins; Proteobacteria; RelA protein; Senescence; Streptococcus infections; Toxins; Toxins, Biological - genetics; Toxins, Biological - metabolism; Virginia; Spain
• DOI: 10.1371/journal.pone.0030282
• EISSN: 1932-6203

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.