Quantifying in vitro B. anthracis growth and PA production and decay: a mathematical modelling approach
Abstract Protective antigen (PA) is a protein produced by Bacillus anthracis. It forms part of the anthrax toxin and is a key immunogen in US and UK anthrax vaccines. In this study, we have conducted experiments to quantify PA in the supernatants of cultures of B. anthracis Sterne strain, which is t...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-03-01
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| Series: | npj Systems Biology and Applications |
| Online Access: | https://doi.org/10.1038/s41540-024-00357-1 |
| _version_ | 1797233466066075648 |
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| author | Bevelynn Williams Jamie Paterson Helena J. Rawsthorne-Manning Polly-Anne Jeffrey Joseph J. Gillard Grant Lythe Thomas R. Laws Martín López-García |
| author_facet | Bevelynn Williams Jamie Paterson Helena J. Rawsthorne-Manning Polly-Anne Jeffrey Joseph J. Gillard Grant Lythe Thomas R. Laws Martín López-García |
| author_sort | Bevelynn Williams |
| collection | DOAJ |
| description | Abstract Protective antigen (PA) is a protein produced by Bacillus anthracis. It forms part of the anthrax toxin and is a key immunogen in US and UK anthrax vaccines. In this study, we have conducted experiments to quantify PA in the supernatants of cultures of B. anthracis Sterne strain, which is the strain used in the manufacture of the UK anthrax vaccine. Then, for the first time, we quantify PA production and degradation via mathematical modelling and Bayesian statistical techniques, making use of this new experimental data as well as two other independent published data sets. We propose a single mathematical model, in terms of delay differential equations (DDEs), which can explain the in vitro dynamics of all three data sets. Since we did not heat activate the B. anthracis spores prior to inoculation, germination occurred much slower in our experiments, allowing us to calibrate two additional parameters with respect to the other data sets. Our model is able to distinguish between natural PA decay and that triggered by bacteria via proteases. There is promising consistency between the different independent data sets for most of the parameter estimates. The quantitative characterisation of B. anthracis PA production and degradation obtained here will contribute towards the ambition to include a realistic description of toxin dynamics, the host immune response, and anti-toxin treatments in future mechanistic models of anthrax infection. |
| first_indexed | 2024-04-24T16:16:37Z |
| format | Article |
| id | doaj.art-7c505df9ca3247c2994f287c4d5b88ec |
| institution | Directory Open Access Journal |
| issn | 2056-7189 |
| language | English |
| last_indexed | 2024-04-24T16:16:37Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Systems Biology and Applications |
| spelling | doaj.art-7c505df9ca3247c2994f287c4d5b88ec2024-03-31T11:24:07ZengNature Portfolionpj Systems Biology and Applications2056-71892024-03-0110111310.1038/s41540-024-00357-1Quantifying in vitro B. anthracis growth and PA production and decay: a mathematical modelling approachBevelynn Williams0Jamie Paterson1Helena J. Rawsthorne-Manning2Polly-Anne Jeffrey3Joseph J. Gillard4Grant Lythe5Thomas R. Laws6Martín López-García7Department of Applied Mathematics, School of Mathematics, University of LeedsDepartment of Applied Mathematics, School of Mathematics, University of LeedsCBR Division, Defence Science and Technology LaboratoryDepartment of Applied Mathematics, School of Mathematics, University of LeedsCBR Division, Defence Science and Technology LaboratoryDepartment of Applied Mathematics, School of Mathematics, University of LeedsCBR Division, Defence Science and Technology LaboratoryDepartment of Applied Mathematics, School of Mathematics, University of LeedsAbstract Protective antigen (PA) is a protein produced by Bacillus anthracis. It forms part of the anthrax toxin and is a key immunogen in US and UK anthrax vaccines. In this study, we have conducted experiments to quantify PA in the supernatants of cultures of B. anthracis Sterne strain, which is the strain used in the manufacture of the UK anthrax vaccine. Then, for the first time, we quantify PA production and degradation via mathematical modelling and Bayesian statistical techniques, making use of this new experimental data as well as two other independent published data sets. We propose a single mathematical model, in terms of delay differential equations (DDEs), which can explain the in vitro dynamics of all three data sets. Since we did not heat activate the B. anthracis spores prior to inoculation, germination occurred much slower in our experiments, allowing us to calibrate two additional parameters with respect to the other data sets. Our model is able to distinguish between natural PA decay and that triggered by bacteria via proteases. There is promising consistency between the different independent data sets for most of the parameter estimates. The quantitative characterisation of B. anthracis PA production and degradation obtained here will contribute towards the ambition to include a realistic description of toxin dynamics, the host immune response, and anti-toxin treatments in future mechanistic models of anthrax infection.https://doi.org/10.1038/s41540-024-00357-1 |
| spellingShingle | Bevelynn Williams Jamie Paterson Helena J. Rawsthorne-Manning Polly-Anne Jeffrey Joseph J. Gillard Grant Lythe Thomas R. Laws Martín López-García Quantifying in vitro B. anthracis growth and PA production and decay: a mathematical modelling approach npj Systems Biology and Applications |
| title | Quantifying in vitro B. anthracis growth and PA production and decay: a mathematical modelling approach |
| title_full | Quantifying in vitro B. anthracis growth and PA production and decay: a mathematical modelling approach |
| title_fullStr | Quantifying in vitro B. anthracis growth and PA production and decay: a mathematical modelling approach |
| title_full_unstemmed | Quantifying in vitro B. anthracis growth and PA production and decay: a mathematical modelling approach |
| title_short | Quantifying in vitro B. anthracis growth and PA production and decay: a mathematical modelling approach |
| title_sort | quantifying in vitro b anthracis growth and pa production and decay a mathematical modelling approach |
| url | https://doi.org/10.1038/s41540-024-00357-1 |
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