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Excitable dynamics through toxin-induced mRNA cleavage in bacteria. / Vet, Stefan; Vandervelde, Alexandra; Gelens, Lendert.

In: PLoS ONE, Vol. 14, No. 2, e0212288, 22.02.2019.

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@article{7c6f1c638e2b487db4aa19b048fbfc23,
title = "Excitable dynamics through toxin-induced mRNA cleavage in bacteria",
abstract = "Toxin-antitoxin (TA) systems in bacteria and archaea are small genetic elements consisting of the genes coding for an intracellular toxin and an antitoxin that can neutralize this toxin. In various cases, the toxins cleave the mRNA. In this theoretical work we use deterministic and stochastic modeling to explain how toxin-induced cleavage of mRNA in TA systems can lead to excitability, allowing large transient spikes in toxin levels to be triggered. By using a simplified network where secondary complex formation and transcriptional regulation are not included, we show that a two-dimensional, deterministic model captures the origin of such toxin excitations. Moreover, it allows to increase our understanding by examining the dynamics in the phase plane. By systematically comparing the deterministic results with Gillespie simulations we demonstrate that even though the real TA system is intrinsically stochastic, toxin excitations can be accurately described deterministically. A bifurcation analysis of the system shows that the excitable behavior is due to a nearby Hopf bifurcation in the parameter space, where the system becomes oscillatory. The influence of stress is modeled by varying the degradation rate of the antitoxin and the translation rate of the toxin. We find that stress increases the frequency of toxin excitations. The inclusion of secondary complex formation and transcriptional regulation does not fundamentally change the mechanism of toxin excitations. Finally, we show that including growth rate suppression and translational inhibition can lead to longer excitations, and even cause excitations in cases when the system would otherwise be non-excitable. To conclude, the deterministic model used in this work provides a simple and intuitive explanation of toxin excitations in TA systems.",
author = "Stefan Vet and Alexandra Vandervelde and Lendert Gelens",
year = "2019",
month = "2",
day = "22",
doi = "10.1371/journal.pone.0212288",
language = "English",
volume = "14",
journal = "PLoS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "2",

}

RIS

TY - JOUR

T1 - Excitable dynamics through toxin-induced mRNA cleavage in bacteria

AU - Vet, Stefan

AU - Vandervelde, Alexandra

AU - Gelens, Lendert

PY - 2019/2/22

Y1 - 2019/2/22

N2 - Toxin-antitoxin (TA) systems in bacteria and archaea are small genetic elements consisting of the genes coding for an intracellular toxin and an antitoxin that can neutralize this toxin. In various cases, the toxins cleave the mRNA. In this theoretical work we use deterministic and stochastic modeling to explain how toxin-induced cleavage of mRNA in TA systems can lead to excitability, allowing large transient spikes in toxin levels to be triggered. By using a simplified network where secondary complex formation and transcriptional regulation are not included, we show that a two-dimensional, deterministic model captures the origin of such toxin excitations. Moreover, it allows to increase our understanding by examining the dynamics in the phase plane. By systematically comparing the deterministic results with Gillespie simulations we demonstrate that even though the real TA system is intrinsically stochastic, toxin excitations can be accurately described deterministically. A bifurcation analysis of the system shows that the excitable behavior is due to a nearby Hopf bifurcation in the parameter space, where the system becomes oscillatory. The influence of stress is modeled by varying the degradation rate of the antitoxin and the translation rate of the toxin. We find that stress increases the frequency of toxin excitations. The inclusion of secondary complex formation and transcriptional regulation does not fundamentally change the mechanism of toxin excitations. Finally, we show that including growth rate suppression and translational inhibition can lead to longer excitations, and even cause excitations in cases when the system would otherwise be non-excitable. To conclude, the deterministic model used in this work provides a simple and intuitive explanation of toxin excitations in TA systems.

AB - Toxin-antitoxin (TA) systems in bacteria and archaea are small genetic elements consisting of the genes coding for an intracellular toxin and an antitoxin that can neutralize this toxin. In various cases, the toxins cleave the mRNA. In this theoretical work we use deterministic and stochastic modeling to explain how toxin-induced cleavage of mRNA in TA systems can lead to excitability, allowing large transient spikes in toxin levels to be triggered. By using a simplified network where secondary complex formation and transcriptional regulation are not included, we show that a two-dimensional, deterministic model captures the origin of such toxin excitations. Moreover, it allows to increase our understanding by examining the dynamics in the phase plane. By systematically comparing the deterministic results with Gillespie simulations we demonstrate that even though the real TA system is intrinsically stochastic, toxin excitations can be accurately described deterministically. A bifurcation analysis of the system shows that the excitable behavior is due to a nearby Hopf bifurcation in the parameter space, where the system becomes oscillatory. The influence of stress is modeled by varying the degradation rate of the antitoxin and the translation rate of the toxin. We find that stress increases the frequency of toxin excitations. The inclusion of secondary complex formation and transcriptional regulation does not fundamentally change the mechanism of toxin excitations. Finally, we show that including growth rate suppression and translational inhibition can lead to longer excitations, and even cause excitations in cases when the system would otherwise be non-excitable. To conclude, the deterministic model used in this work provides a simple and intuitive explanation of toxin excitations in TA systems.

UR - http://www.scopus.com/inward/record.url?scp=85061960607&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0212288

DO - 10.1371/journal.pone.0212288

M3 - Article

VL - 14

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 2

M1 - e0212288

ER -

ID: 44416013