title: pSM19035-encoded zeta toxin induces stasis followed by death in a subpopulation of cells.
abstract: The toxin-antitoxin operon of pSM19035 encodes three proteins: the omega global regulator, the epsilon labile antitoxin and the stable zeta toxin. Accumulation of zeta toxin free of epsilon antitoxin induced loss of cell proliferation in both Bacillus subtilis and Escherichia coli cells. Induction of a zeta variant (zetaY83C) triggered stasis, in which B. subtilis cells were viable but unable to proliferate, without selectively affecting protein translation. In E. coli cells, accumulation of free zeta toxin induced stasis, but this was fully reversed by expression of the epsilon antitoxin within a defined time window. The time window for reversion of zeta toxicity by expression of epsilon antitoxin was dependent on the initial cellular level of zeta. After 240 min of constitutive expression, or inducible expression of high levels of zeta toxin for 30 min, expression of epsilon failed to reverse the toxic effect exerted by zeta in cells growing in minimal medium. Under the latter conditions, zeta inhibited replication, transcription and translation and finally induced death in a fraction (approximately 50 %) of the cell population. These results support the view that zeta interacts with its specific target and reversibly inhibits cell proliferation, but accumulation of zeta might lead to cell death due to pleiotropic effects.
authors.affiliation: Department of Microbial Biotechnology, Centro Nacional de Biotecnología, CSIC, 28049 Madrid, Spain.
authors.forename: Virginia S
authors.initials: VS
authors.lastname: Lioy
authors.affiliation: Department of Microbial Biotechnology, Centro Nacional de Biotecnología, CSIC, 28049 Madrid, Spain.
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Martín
authors.affiliation: Department of Microbial Biotechnology, Centro Nacional de Biotecnología, CSIC, 28049 Madrid, Spain.
authors.forename: Ana G
authors.initials: AG
authors.lastname: Camacho
authors.affiliation: Max-Planck-Institut für molekulare Genetik, D-14195 Berlin, Germany.
authors.forename: Rudi
authors.initials: R
authors.lastname: Lurz
authors.affiliation: Institut für Mikrobiologie, Ernst-Moritz-Arndt-Universität, D-17487 Greifswald, Greifswald, Germany.
authors.forename: Haike
authors.initials: H
authors.lastname: Antelmann
authors.affiliation: Institut für Mikrobiologie, Ernst-Moritz-Arndt-Universität, D-17487 Greifswald, Greifswald, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hecker
authors.affiliation: Department of Food Safety Science, BBSRC Institute of Food Research, Norwich Laboratory, Colney Lane, Norwich Research Park, Colney, Norwich NR4 7UA, UK.
authors.forename: Ed
authors.initials: E
authors.lastname: Hitchin
authors.affiliation: Department of Food Safety Science, BBSRC Institute of Food Research, Norwich Laboratory, Colney Lane, Norwich Research Park, Colney, Norwich NR4 7UA, UK.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Ridge
authors.affiliation: University of Amsterdam, Swammerdam Institute of Life Sciences, 1018 WV Amsterdam, The Netherlands.|Department of Food Safety Science, BBSRC Institute of Food Research, Norwich Laboratory, Colney Lane, Norwich Research Park, Colney, Norwich NR4 7UA, UK.
authors.forename: Jerry M
authors.initials: JM
authors.lastname: Wells
authors.affiliation: Department of Microbial Biotechnology, Centro Nacional de Biotecnología, CSIC, 28049 Madrid, Spain.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Alonso
mesh_terms: D000992:Antitoxins / Q000502:physiology; D017209:Apoptosis; D001412:Bacillus subtilis / Q000235:genetics* / Q000502:physiology; D001427:Bacterial Toxins / Q000235:genetics*; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D004269:DNA, Bacterial / Q000096:biosynthesis; D004926:Escherichia coli / Q000235:genetics* / Q000502:physiology; D015964:Gene Expression Regulation, Bacterial; D009876:Operon; D010957:Plasmids / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D000992:Antitoxins; D001427:Bacterial Toxins; D004269:DNA, Bacterial