Chalmers Conferences, 9th European Conference on Mathematical and Theoretical Biology

Toxin-Antitoxin Battle in Bacteria
Namiko Mitarai

Last modified: 2014-06-09


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.