The ζ Toxin Induces a Set of Protective Responses and Dormancy

The zeta epsilon module consists of a labile antitoxin protein, e, which in dimer form (epsilon(2)) interferes with the action of the long-living monomeric zeta phosphotransferase toxin through protein complex formation. Toxin zeta, 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 (1-5x10(-5)). Early after induction zeta toxin alters the expression of similar to 78 genes, with the up-regulation of relA among them. RelA contributes to enforce toxin-induced dormancy. At later times, free active zeta decreases synthesis of macromolecules and releases intracellular K+. We propose that zeta toxin induces reversible protective dormancy and permeation to PI, and expression of epsilon(2) antitoxin reverses these effects. At later times, toxin expression is followed by death of a small fraction (similar to 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 epsilon(2) antitoxin, which blocks ATP binding by zeta toxin, thereby inhibiting its phosphotransferase activity.