Conditional cooperativity of toxin - antitoxin regulation can mediate bistability between growth and dormancy.

• Main Authors: Ilaria Cataudella, Kim Sneppen, Kenn Gerdes, Namiko Mitarai
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2013-01-01
• Series: PLoS Computational Biology
• Online Access: http://europepmc.org/articles/PMC3757081?pdf=render

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.