Toxin-Antitoxin Battle in Bacteria
Last modified: 2014-06-09
Abstract
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.
References:
[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.
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.
References:
[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.