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Published on: January 9, 2013
Game theoretical modelling of survival strategies of Candida albicans inside macrophages
S Hummert1, C Hummert, A Schröter
1Friedrich-Schiller University, School of Biology and Pharmaceutics, Ernst-Abbe-Platz 2, D-07743 Jena, Germany. sabine.hummert@uni-jena.de
Abstract:
The polymorphic fungus Candida albicans can live as an aggressive pathogen that causes a wide variety of diseases in humans. Host resistance against these infections is mediated predominantly by phagocytes, namely neutrophils and macrophages. This report provides two game theoretical models of ingested C. albicans cells in macrophages. Two strategies are available for each pathogenic yeast cell: avoiding lysis transiently (called silencing) or forming hyphae and escaping (called piercing because the macrophage is pierced from inside). In dependence on parameter values, two different outcomes can be derived from the model: when the difference of the costs of the two strategies is low, all fungal cells inside a macrophage will play the piercing strategy, while in the high-cost case, a mixed population of piercing and silencing cells is the only stable solution. Further, the role of the SAP gene family encoding secreted proteinases and the Sap proteins is investigated with the help of known studies and is put in relation to the costs of the strategies, the most important parameter of this model. Our results are in agreement with wet-lab results presented by other groups and the model parameters can be estimated from experimental data.
Insights
This study models Candida albicans strategies within macrophages. Depending on costs, the fungus either pierces macrophages or a mix of strategies emerges, aligning with experimental data.
Area of Science:
- Mycology
- Immunology
- Mathematical Biology
Background:
- Candida albicans is a polymorphic fungus and opportunistic human pathogen.
- Phagocytes, such as neutrophils and macrophages, are key in host defense against C. albicans infections.
- Understanding pathogen-host interactions at a cellular level is crucial for developing effective treatments.
Purpose of the Study:
- To develop game theoretical models simulating the behavior of Candida albicans within macrophages.
- To analyze the strategies of C. albicans: 'silencing' to avoid lysis and 'piercing' to escape by forming hyphae.
- To investigate the influence of the SAP gene family and secreted proteinases on these strategies.
Main Methods:
- Development of two game theoretical models to represent C. albicans interactions within macrophages.
- Analysis of two distinct strategies: 'silencing' (avoiding lysis) and 'piercing' (hyphal escape).
- Integration of existing research on the SAP gene family and Sap proteins into the model.
Main Results:
- Model outcomes depend on the relative costs of the two strategies.
- Low cost differences lead to a 'piercing' strategy dominance.
- High cost differences result in a stable mixed population of 'piercing' and 'silencing' cells.
- The role of SAP genes and proteins is linked to the cost parameters.
Conclusions:
- The game theoretical models provide insights into C. albicans survival strategies within macrophages.
- Model predictions align with experimental findings from other research groups.
- The study suggests that model parameters can be estimated from experimental data, facilitating further research.
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