Projects per year
Abstract
Toxin-Antitoxin modules are small operons involved in stress response and persister cell formation that encode a "toxin" and its corresponding neutralizing "antitoxin". Regulation of these modules involves a complex mechanism known as conditional cooperativity, which is supposed to prevent unwanted toxin activation. Here we develop mathematical models for their regulation, based on published molecular and structural data, and parameterized using experimental data for F-plasmid ccdAB, bacteriophage P1 phd/doc and E. coli relBE. We show that the level of free toxin in the cell is mainly controlled through toxin sequestration in toxin-antitoxin complexes of various stoichiometry rather than by gene regulation. If the toxin translation rate exceeds twice the antitoxin translation rate, toxins accumulate in all cells. Conditional cooperativity and increasing the number of binding sites on the operator serves to reduce the metabolic burden of the cell by reducing the total amounts of proteins produced. Combining conditional cooperativity and bridging of antitoxins by toxins when bound to their operator sites allows creation of persister cells through rare, extreme stochastic spikes in the free toxin level. The amplitude of these spikes determines the duration of the persister state. Finally, increases in the antitoxin degradation rate and decreases in the bacterial growth rate cause a rise in the amount of persisters during nutritional stress.
Original language | English |
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Pages (from-to) | 1003190 |
Number of pages | 1 |
Journal | PLoS Comp Biol |
Volume | 9 |
Publication status | Published - 2013 |
Keywords
- Computational biology
- Systems biology
- Toxin-antitoxin module
- Persister
- Transcription regulation
Fingerprint
Dive into the research topics of 'A general model for toxin-antitoxin module dynamics can explain persister cell formation in E. coli.'. Together they form a unique fingerprint.Projects
- 3 Finished
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SRP13: Strategic Research Programme: Structure and dynamics of macromolecular complexes in health and disease
Steyaert, J., Remaut, H. K., Loris, R., Efremov, R., Steyaert, J., Loris, R. & Remaut, H. K.
1/11/12 → 31/10/24
Project: Fundamental
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FWOTM637: New mechanisms of transcription regulation in prokaryotes
1/10/12 → 30/09/16
Project: Fundamental
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FWOAL633: Dynamics of toxin-antitoxin stress response networks: an interdisciplinarycomputational and in-vivo approach.
1/01/12 → 31/12/15
Project: Fundamental
Activities
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6th FEMS Congress of european Microbiologists
Remy Loris (Invited speaker)
8 Jun 2015Activity: Talk or presentation › Talk or presentation at a conference
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6th FEMS Congress of European Microbiologists
Remy Loris (Invited speaker)
6 Jun 2015 → 11 Jun 2015Activity: Talk or presentation › Talk or presentation at a conference
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VIB Seminar 2014
Alexandra Vandervelde (Participant)
28 Apr 2014 → 30 Apr 2014Activity: Participating in or organising an event › Participation in workshop, seminar