PLoS Computational Biology (Jan 2013)

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

  • Ilaria Cataudella,
  • Kim Sneppen,
  • Kenn Gerdes,
  • Namiko Mitarai

DOI
https://doi.org/10.1371/journal.pcbi.1003174
Journal volume & issue
Vol. 9, no. 8
p. e1003174

Abstract

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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.