Speaker
Namiko Mitarai
(The Niels Bohr Institute)
Description
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.
