An Integrative Approach to Computational Modelling of the Gene Regulatory Network Controlling Clostridium botulinum Type A1 Toxin Production.
Clostridium botulinum produces botulinum neurotoxins (BoNTs), highly potent substances responsible for botulism. Currently, mathematical models of C. botulinum growth and toxigenesis are largely aimed at risk assessment and do not include explicit genetic information beyond group level but integrate...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2016-11-01
|
| Series: | PLoS Computational Biology |
| Online Access: | http://europepmc.org/articles/PMC5113860?pdf=render |
| _version_ | 1819079652156637184 |
|---|---|
| author | Adaoha E C Ihekwaba Ivan Mura John Walshaw Michael W Peck Gary C Barker |
| author_facet | Adaoha E C Ihekwaba Ivan Mura John Walshaw Michael W Peck Gary C Barker |
| author_sort | Adaoha E C Ihekwaba |
| collection | DOAJ |
| description | Clostridium botulinum produces botulinum neurotoxins (BoNTs), highly potent substances responsible for botulism. Currently, mathematical models of C. botulinum growth and toxigenesis are largely aimed at risk assessment and do not include explicit genetic information beyond group level but integrate many component processes, such as signalling, membrane permeability and metabolic activity. In this paper we present a scheme for modelling neurotoxin production in C. botulinum Group I type A1, based on the integration of diverse information coming from experimental results available in the literature. Experiments show that production of BoNTs depends on the growth-phase and is under the control of positive and negative regulatory elements at the intracellular level. Toxins are released as large protein complexes and are associated with non-toxic components. Here, we systematically review and integrate those regulatory elements previously described in the literature for C. botulinum Group I type A1 into a population dynamics model, to build the very first computational model of toxin production at the molecular level. We conduct a validation of our model against several items of published experimental data for different wild type and mutant strains of C. botulinum Group I type A1. The result of this process underscores the potential of mathematical modelling at the cellular level, as a means of creating opportunities in developing new strategies that could be used to prevent botulism; and potentially contribute to improved methods for the production of toxin that is used for therapeutics. |
| first_indexed | 2024-12-21T19:32:23Z |
| format | Article |
| id | doaj.art-b31355ecdeb440448104c80aa4b5e391 |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-12-21T19:32:23Z |
| publishDate | 2016-11-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-b31355ecdeb440448104c80aa4b5e3912022-12-21T18:52:40ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582016-11-011211e100520510.1371/journal.pcbi.1005205An Integrative Approach to Computational Modelling of the Gene Regulatory Network Controlling Clostridium botulinum Type A1 Toxin Production.Adaoha E C IhekwabaIvan MuraJohn WalshawMichael W PeckGary C BarkerClostridium botulinum produces botulinum neurotoxins (BoNTs), highly potent substances responsible for botulism. Currently, mathematical models of C. botulinum growth and toxigenesis are largely aimed at risk assessment and do not include explicit genetic information beyond group level but integrate many component processes, such as signalling, membrane permeability and metabolic activity. In this paper we present a scheme for modelling neurotoxin production in C. botulinum Group I type A1, based on the integration of diverse information coming from experimental results available in the literature. Experiments show that production of BoNTs depends on the growth-phase and is under the control of positive and negative regulatory elements at the intracellular level. Toxins are released as large protein complexes and are associated with non-toxic components. Here, we systematically review and integrate those regulatory elements previously described in the literature for C. botulinum Group I type A1 into a population dynamics model, to build the very first computational model of toxin production at the molecular level. We conduct a validation of our model against several items of published experimental data for different wild type and mutant strains of C. botulinum Group I type A1. The result of this process underscores the potential of mathematical modelling at the cellular level, as a means of creating opportunities in developing new strategies that could be used to prevent botulism; and potentially contribute to improved methods for the production of toxin that is used for therapeutics.http://europepmc.org/articles/PMC5113860?pdf=render |
| spellingShingle | Adaoha E C Ihekwaba Ivan Mura John Walshaw Michael W Peck Gary C Barker An Integrative Approach to Computational Modelling of the Gene Regulatory Network Controlling Clostridium botulinum Type A1 Toxin Production. PLoS Computational Biology |
| title | An Integrative Approach to Computational Modelling of the Gene Regulatory Network Controlling Clostridium botulinum Type A1 Toxin Production. |
| title_full | An Integrative Approach to Computational Modelling of the Gene Regulatory Network Controlling Clostridium botulinum Type A1 Toxin Production. |
| title_fullStr | An Integrative Approach to Computational Modelling of the Gene Regulatory Network Controlling Clostridium botulinum Type A1 Toxin Production. |
| title_full_unstemmed | An Integrative Approach to Computational Modelling of the Gene Regulatory Network Controlling Clostridium botulinum Type A1 Toxin Production. |
| title_short | An Integrative Approach to Computational Modelling of the Gene Regulatory Network Controlling Clostridium botulinum Type A1 Toxin Production. |
| title_sort | integrative approach to computational modelling of the gene regulatory network controlling clostridium botulinum type a1 toxin production |
| url | http://europepmc.org/articles/PMC5113860?pdf=render |
| work_keys_str_mv | AT adaohaecihekwaba anintegrativeapproachtocomputationalmodellingofthegeneregulatorynetworkcontrollingclostridiumbotulinumtypea1toxinproduction AT ivanmura anintegrativeapproachtocomputationalmodellingofthegeneregulatorynetworkcontrollingclostridiumbotulinumtypea1toxinproduction AT johnwalshaw anintegrativeapproachtocomputationalmodellingofthegeneregulatorynetworkcontrollingclostridiumbotulinumtypea1toxinproduction AT michaelwpeck anintegrativeapproachtocomputationalmodellingofthegeneregulatorynetworkcontrollingclostridiumbotulinumtypea1toxinproduction AT garycbarker anintegrativeapproachtocomputationalmodellingofthegeneregulatorynetworkcontrollingclostridiumbotulinumtypea1toxinproduction AT adaohaecihekwaba integrativeapproachtocomputationalmodellingofthegeneregulatorynetworkcontrollingclostridiumbotulinumtypea1toxinproduction AT ivanmura integrativeapproachtocomputationalmodellingofthegeneregulatorynetworkcontrollingclostridiumbotulinumtypea1toxinproduction AT johnwalshaw integrativeapproachtocomputationalmodellingofthegeneregulatorynetworkcontrollingclostridiumbotulinumtypea1toxinproduction AT michaelwpeck integrativeapproachtocomputationalmodellingofthegeneregulatorynetworkcontrollingclostridiumbotulinumtypea1toxinproduction AT garycbarker integrativeapproachtocomputationalmodellingofthegeneregulatorynetworkcontrollingclostridiumbotulinumtypea1toxinproduction |