Stochastic dynamics of Francisella tularensis infection and replication.
We study the pathogenesis of Francisella tularensis infection with an experimental mouse model, agent-based computation and mathematical analysis. Following inhalational exposure to Francisella tularensis SCHU S4, a small initial number of bacteria enter lung host cells and proliferate inside them,...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2020-06-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://doi.org/10.1371/journal.pcbi.1007752 |
| _version_ | 1818901894068699136 |
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| author | Jonathan Carruthers Grant Lythe Martín López-García Joseph Gillard Thomas R Laws Roman Lukaszewski Carmen Molina-París |
| author_facet | Jonathan Carruthers Grant Lythe Martín López-García Joseph Gillard Thomas R Laws Roman Lukaszewski Carmen Molina-París |
| author_sort | Jonathan Carruthers |
| collection | DOAJ |
| description | We study the pathogenesis of Francisella tularensis infection with an experimental mouse model, agent-based computation and mathematical analysis. Following inhalational exposure to Francisella tularensis SCHU S4, a small initial number of bacteria enter lung host cells and proliferate inside them, eventually destroying the host cell and releasing numerous copies that infect other cells. Our analysis of disease progression is based on a stochastic model of a population of infectious agents inside one host cell, extending the birth-and-death process by the occurrence of catastrophes: cell rupture events that affect all bacteria in a cell simultaneously. Closed expressions are obtained for the survival function of an infected cell, the number of bacteria released as a function of time after infection, and the total bacterial load. We compare our mathematical analysis with the results of agent-based computation and, making use of approximate Bayesian statistical inference, with experimental measurements carried out after murine aerosol infection with the virulent SCHU S4 strain of the bacterium Francisella tularensis, that infects alveolar macrophages. The posterior distribution of the rate of replication of intracellular bacteria is consistent with the estimate that the time between rounds of bacterial division is less than 6 hours in vivo. |
| first_indexed | 2024-12-19T20:27:00Z |
| format | Article |
| id | doaj.art-e2daf406902b443a837ceb5c6a22e7d7 |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-12-19T20:27:00Z |
| publishDate | 2020-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-e2daf406902b443a837ceb5c6a22e7d72022-12-21T20:06:48ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582020-06-01166e100775210.1371/journal.pcbi.1007752Stochastic dynamics of Francisella tularensis infection and replication.Jonathan CarruthersGrant LytheMartín López-GarcíaJoseph GillardThomas R LawsRoman LukaszewskiCarmen Molina-ParísWe study the pathogenesis of Francisella tularensis infection with an experimental mouse model, agent-based computation and mathematical analysis. Following inhalational exposure to Francisella tularensis SCHU S4, a small initial number of bacteria enter lung host cells and proliferate inside them, eventually destroying the host cell and releasing numerous copies that infect other cells. Our analysis of disease progression is based on a stochastic model of a population of infectious agents inside one host cell, extending the birth-and-death process by the occurrence of catastrophes: cell rupture events that affect all bacteria in a cell simultaneously. Closed expressions are obtained for the survival function of an infected cell, the number of bacteria released as a function of time after infection, and the total bacterial load. We compare our mathematical analysis with the results of agent-based computation and, making use of approximate Bayesian statistical inference, with experimental measurements carried out after murine aerosol infection with the virulent SCHU S4 strain of the bacterium Francisella tularensis, that infects alveolar macrophages. The posterior distribution of the rate of replication of intracellular bacteria is consistent with the estimate that the time between rounds of bacterial division is less than 6 hours in vivo.https://doi.org/10.1371/journal.pcbi.1007752 |
| spellingShingle | Jonathan Carruthers Grant Lythe Martín López-García Joseph Gillard Thomas R Laws Roman Lukaszewski Carmen Molina-París Stochastic dynamics of Francisella tularensis infection and replication. PLoS Computational Biology |
| title | Stochastic dynamics of Francisella tularensis infection and replication. |
| title_full | Stochastic dynamics of Francisella tularensis infection and replication. |
| title_fullStr | Stochastic dynamics of Francisella tularensis infection and replication. |
| title_full_unstemmed | Stochastic dynamics of Francisella tularensis infection and replication. |
| title_short | Stochastic dynamics of Francisella tularensis infection and replication. |
| title_sort | stochastic dynamics of francisella tularensis infection and replication |
| url | https://doi.org/10.1371/journal.pcbi.1007752 |
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