title: Conditional cooperativity of toxin - antitoxin regulation can mediate bistability between growth and dormancy.
abstract: Many toxin-antitoxin operons are regulated by the toxin/antitoxin ratio by mechanisms collectively coined "conditional cooperativity". Toxin and antitoxin form heteromers with different stoichiometric ratios, and the complex with the intermediate ratio works best as a transcription repressor. This allows transcription at low toxin level, strong repression at intermediate toxin level, and then again transcription at high toxin level. Such regulation has two interesting features; firstly, it provides a non-monotonous response to the concentration of one of the proteins, and secondly, it opens for ultra-sensitivity mediated by the sequestration of the functioning heteromers. We explore possible functions of conditional regulation in simple feedback motifs, and show that it can provide bistability for a wide range of parameters. We then demonstrate that the conditional cooperativity in toxin-antitoxin systems combined with the growth-inhibition activity of free toxin can mediate bistability between a growing state and a dormant state.
authors.affiliation: Niels Bohr Institute/CMOL, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Cataudella
authors.forename: Kim
authors.initials: K
authors.lastname: Sneppen
authors.forename: Kenn
authors.initials: K
authors.lastname: Gerdes
authors.forename: Namiko
authors.initials: N
authors.lastname: Mitarai
mesh_terms: D018407:Bacterial Physiological Phenomena; D001427:Bacterial Toxins / Q000378:metabolism*; D019295:Computational Biology; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000502:physiology; D029968:Escherichia coli Proteins / Q000502:physiology; D025461:Feedback, Physiological / Q000502:physiology; D008954:Models, Biological
chemical_list: D001427:Bacterial Toxins; D029968:Escherichia coli Proteins