Mar 26 – 28, 2014
Nordita, Stockholm
Europe/Stockholm timezone

Conditional Cooperativity in Toxin-Antitoxin Battle in Bacteria

Mar 28, 2014, 11:30 AM
132:028 (Nordita, Stockholm)


Nordita, Stockholm


Namiko Mitarai (The Niels Bohr Institute)


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 toxinlevel, and then again transcription at high toxin level ([1] and references therein). 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 wide a range of parameters [2]. We 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. Conditional cooperativity also secures that the antitoxin dominated state has a substantial amount of toxins present, which helps the transition to the toxin dominated state under stress. These features may be relevant for understanding persister formation in E. coli. [1] I. Cataudella, A.Trusina, K. Sneppen, K. Gerdes, and N. Mitarai, Nucl. Acids Res. (2012) 40, 6424-6434. [2] I. Cataudella, K. Sneppen, K. Gerdes, and N. Mitarai, Plos. Comput. Biol. (2013) 8, e1003174.

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