Gupta2019 - Restoration of cytosolic calcium inhibits Mycobacterium tuberculosis intracellular growth
Model Identifier
MODEL1911120004
Short description
This is a four dimensionsal ordinary differential equation mathematical model that explores the contribution of PI3P during Mycobacterium tuberculosis (Mtb) phagocytosis. The model was built in an effort to understand the mechanisms by which Mtb eliminates phagosome-lysosome fusion during the hosts enactment of anti-microbial pathways.
Format
SBML
(L2V4)
Related Publication
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Restoration of cytosolic calcium inhibits Mycobacterium tuberculosis intracellular growth: Theoretical evidence and experimental observation.
- Gupta A, Das PN, Bouzeyen R, Karmakar SP, Singh R, Bairagi N, Chatterjee S
- Journal of theoretical biology , 7/ 2019 , Volume 472 , pages: 110-123 , PubMed ID: 31002776
- Drug Discovery Research Centre, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad 121001, India.
- Mycobacterium tuberculosis (Mtb) is a highly successful intracellular pathogen because of its ability to modulate host's anti-microbial pathways. Phagocytosis acts as the first line of defence against microbial infection. However, Mtb inhibits Phosphatidylinositol 3-phosphate (PI3P) oscillations which is required for phagolysosomal fusion. Here we attempted to understand the mechanisms by which Mtb eliminates phagosome-lysosome fusion. To address this, we built a four dimensional ordinary differential equation model and explored the contribution of PI3P during Mtb phagocytosis. Using this model, we identified some sensitive parameters that influence the dynamics of host-pathogen interactions. We observed that PI3P dynamics can be controlled by regulating the intracellular calcium oscillations. Some plausible methods to restore PI3P oscillations are ER flux rate, recruitment rate of proteins, like Rab GTPase, and cooperativity coefficient of calcium dependent consumption of calmodulin. Further, we investigated whether modulation of these pathways is a potential therapeutic intervention strategy. Here we showed that RyR2 agonist caffeine stimulated calcium influx and inhibited growth of intracellular Mtb in macrophages. Taken together, we demonstrate that modulation of host calcium level is a plausible strategy for killing of intracellular Mtb.
Contributors
Submitter of the first revision: Johannes Meyer
Submitter of this revision: Johannes Meyer
Modellers: Johannes Meyer
Submitter of this revision: Johannes Meyer
Modellers: Johannes Meyer
Metadata information
hasProperty (2 statements)
Mathematical Modelling Ontology
Ordinary differential equation model
ChEBI phosphatidylinositol 3-phosphate
ChEBI phosphatidylinositol 3-phosphate
Curation status
Non-curated
Modelling approach(es)
Tags
Connected external resources
SBGN view in Newt Editor
| Name | Description | Size | Actions |
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Model files |
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| Gupta2019.xml | SBML L2V4 Representation of Gupta2019 - Restoration of cytosolic calcium inhibits Mycobacterium tuberculosis intracellular growth | 36.84 KB | Preview | Download |
Additional files |
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| Gupta2019.cps | COPASI file of Gupta2019 - Restoration of cytosolic calcium inhibits Mycobacterium tuberculosis intracellular growth | 90.78 KB | Preview | Download |
- Model originally submitted by : Johannes Meyer
- Submitted: Nov 12, 2019 1:33:36 PM
- Last Modified: Nov 12, 2019 1:33:36 PM
Revisions
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Version: 1
- Submitted on: Nov 12, 2019 1:33:36 PM
- Submitted by: Johannes Meyer
- With comment: Import of Gupta2019 - Restoration of cytosolic calcium inhibits Mycobacterium tuberculosis intracellular growth