Mathematical modelling of SigE regulatory network reveals new insights into bistability of mycobacterial stress response

Abstract Background The ability to rapidly adapt to adverse environmental conditions represents the key of success of many pathogens and, in particular, of Mycobacterium tuberculosis. Upon exposition to heat shock, antibiotics or other sources of stress, appropriate responses in terms of genes trans...

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Autores principales:	Irene Zorzan, Simone Del Favero, Alberto Giaretta, Riccardo Manganelli, Barbara Di Camillo, Luca Schenato
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Bacterial persistence Mathematical modelling Bistability Computer applications to medicine. Medical informatics R858-859.7 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/1637dde49e354be6a47509485221a57d
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spelling	oai:doaj.org-article:1637dde49e354be6a47509485221a57d2021-11-21T12:09:17ZMathematical modelling of SigE regulatory network reveals new insights into bistability of mycobacterial stress response10.1186/s12859-021-04372-51471-2105https://doaj.org/article/1637dde49e354be6a47509485221a57d2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12859-021-04372-5https://doaj.org/toc/1471-2105Abstract Background The ability to rapidly adapt to adverse environmental conditions represents the key of success of many pathogens and, in particular, of Mycobacterium tuberculosis. Upon exposition to heat shock, antibiotics or other sources of stress, appropriate responses in terms of genes transcription and proteins activity are activated leading part of a genetically identical bacterial population to express a different phenotype, namely to develop persistence. When the stress response network is mathematically described by an ordinary differential equations model, development of persistence in the bacterial population is associated with bistability of the model, since different emerging phenotypes are represented by different stable steady states. Results In this work, we develop a mathematical model of SigE stress response network that incorporates interactions not considered in mathematical models currently available in the literature. We provide, through involved analytical computations, accurate approximations of the system’s nullclines, and exploit the obtained expressions to determine, in a reliable though computationally efficient way, the number of equilibrium points of the system. Conclusions Theoretical analysis and perturbation experiments point out the crucial role played by the degradation pathway involving RseA, the anti-sigma factor of SigE, for coexistence of two stable equilibria and the emergence of bistability. Our results also indicate that a fine control on RseA concentration is a necessary requirement in order for the system to exhibit bistability.Irene ZorzanSimone Del FaveroAlberto GiarettaRiccardo ManganelliBarbara Di CamilloLuca SchenatoBMCarticleBacterial persistenceMathematical modellingBistabilityComputer applications to medicine. Medical informaticsR858-859.7Biology (General)QH301-705.5ENBMC Bioinformatics, Vol 22, Iss 1, Pp 1-29 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Bacterial persistence Mathematical modelling Bistability Computer applications to medicine. Medical informatics R858-859.7 Biology (General) QH301-705.5
spellingShingle	Bacterial persistence Mathematical modelling Bistability Computer applications to medicine. Medical informatics R858-859.7 Biology (General) QH301-705.5 Irene Zorzan Simone Del Favero Alberto Giaretta Riccardo Manganelli Barbara Di Camillo Luca Schenato Mathematical modelling of SigE regulatory network reveals new insights into bistability of mycobacterial stress response
description	Abstract Background The ability to rapidly adapt to adverse environmental conditions represents the key of success of many pathogens and, in particular, of Mycobacterium tuberculosis. Upon exposition to heat shock, antibiotics or other sources of stress, appropriate responses in terms of genes transcription and proteins activity are activated leading part of a genetically identical bacterial population to express a different phenotype, namely to develop persistence. When the stress response network is mathematically described by an ordinary differential equations model, development of persistence in the bacterial population is associated with bistability of the model, since different emerging phenotypes are represented by different stable steady states. Results In this work, we develop a mathematical model of SigE stress response network that incorporates interactions not considered in mathematical models currently available in the literature. We provide, through involved analytical computations, accurate approximations of the system’s nullclines, and exploit the obtained expressions to determine, in a reliable though computationally efficient way, the number of equilibrium points of the system. Conclusions Theoretical analysis and perturbation experiments point out the crucial role played by the degradation pathway involving RseA, the anti-sigma factor of SigE, for coexistence of two stable equilibria and the emergence of bistability. Our results also indicate that a fine control on RseA concentration is a necessary requirement in order for the system to exhibit bistability.
format	article
author	Irene Zorzan Simone Del Favero Alberto Giaretta Riccardo Manganelli Barbara Di Camillo Luca Schenato
author_facet	Irene Zorzan Simone Del Favero Alberto Giaretta Riccardo Manganelli Barbara Di Camillo Luca Schenato
author_sort	Irene Zorzan
title	Mathematical modelling of SigE regulatory network reveals new insights into bistability of mycobacterial stress response
title_short	Mathematical modelling of SigE regulatory network reveals new insights into bistability of mycobacterial stress response
title_full	Mathematical modelling of SigE regulatory network reveals new insights into bistability of mycobacterial stress response
title_fullStr	Mathematical modelling of SigE regulatory network reveals new insights into bistability of mycobacterial stress response
title_full_unstemmed	Mathematical modelling of SigE regulatory network reveals new insights into bistability of mycobacterial stress response
title_sort	mathematical modelling of sige regulatory network reveals new insights into bistability of mycobacterial stress response
publisher	BMC
publishDate	2021
url	https://doaj.org/article/1637dde49e354be6a47509485221a57d
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Mathematical modelling of SigE regulatory network reveals new insights into bistability of mycobacterial stress response

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