title: Conditional cooperativity in toxin-antitoxin regulation prevents random toxin activation and promotes fast translational recovery.
abstract: Many toxin-antitoxin (TA) loci are known to strongly repress their own transcription. This auto-inhibition is often called 'conditional cooperativity' as it relies on cooperative binding of TA complexes to operator DNA that occurs only when toxins are in a proper stoichiometric relationship with antitoxins. There has recently been an explosion of interest in TA systems due to their role in bacterial persistence, however the role of conditional cooperativity is still unclear. We reveal the biological function of conditional cooperativity by constructing a mathematical model of the well studied TA system, relBE of Escherichia coli. We show that the model with the in vivo and in vitro established parameters reproduces experimentally observed response to nutritional stress. We further demonstrate that conditional cooperativity stabilizes the level of antitoxin in rapidly growing cells such that random induction of relBE is minimized. At the same time it enables quick removal of free toxin when the starvation is terminated.
authors.affiliation: Center for Models of Life, Niels Bohr Institute, University of Copenhagen, Blegdamsvej 17, DK-2100 Copenhagen, Denmark. cataudel@nbi.dk
authors.forename: Ilaria
authors.initials: I
authors.lastname: Cataudella
authors.forename: Ala
authors.initials: A
authors.lastname: Trusina
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: D000596:Amino Acids / Q000378:metabolism; D001427:Bacterial Toxins / Q000235:genetics* / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006706:Homeostasis; D008957:Models, Genetic; D014176:Protein Biosynthesis; D014158:Transcription, Genetic; D051841:Transcription Factor RelB
chemical_list: D000596:Amino Acids; D001427:Bacterial Toxins; D029968:Escherichia coli Proteins; C465567:RelB protein, E coli; D051841:Transcription Factor RelB; C465566:RelE protein, E coli