Conditional Cooperativity of Toxin - Antitoxin Regulation Can Mediate Bistability between Growth and Dormancy

TY - JOUR

T1 - Conditional Cooperativity of Toxin - Antitoxin Regulation Can Mediate Bistability between Growth and Dormancy

AU - Cataudella, Ilaria

AU - Sneppen, Kim

AU - Gerdes, Kenn

AU - Mitarai, Namiko

PY - 2013/8/1

Y1 - 2013/8/1

N2 - 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.

AB - 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.

U2 - 10.1371/journal.pcbi.1003174

DO - 10.1371/journal.pcbi.1003174

M3 - Journal article

C2 - 24009488

SN - 1553-734X

VL - 9

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 8

M1 - e1003174

ER -