Conditional Cooperativity in Toxin-Antitoxin Regulation Prevents Random Toxin Activation and Promotes Fast Translational Recovery

TY - JOUR

T1 - Conditional Cooperativity in Toxin-Antitoxin Regulation Prevents Random Toxin Activation and Promotes Fast Translational Recovery

AU - Cataudella, Ilaria

AU - Trusina, Ala

AU - Sneppen, Kim

AU - Gerdes, Kenn

AU - Mitarai, Namiko

PY - 2012/8

Y1 - 2012/8

N2 - 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.

AB - 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.

U2 - 10.1093/nar/gks297

DO - 10.1093/nar/gks297

M3 - Journal article

SN - 0305-1048

VL - 40

SP - 6424

EP - 6434

JO - Nucleic Acids Research

JF - Nucleic Acids Research

IS - 14

ER -