Game theoretical modelling of survival strategies of Candida albicans inside macrophages

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.

Identification of Infection- and Defense-Related Genes via a Dynamic Host-Pathogen Interaction Network Using a Candida Albicans-Zebrafish Infection Model

“…We used the GO database to select 195 cell surface proteins from the 4,031-protein pool to build the resultant protein pool for C. albicans . Because host resistance against C. albicans infections is mediated predominantly by phagocytes, namely neutrophils and macrophages [23,24], we assumed that cell surface proteins of C. albicans may interact with any protein of zebrafish in the infectious process. So, we let x ⇀ = ( x 1 ,..., x N ) denote the gene expression time profile of C. albicans cell surface protein x and y ⇀ = ( y 1 ,...., y N ) denote the gene expression time profile of zebrafish protein y.…”

Facing the challenges of multiscale modelling of bacterial and fungal pathogen–host interactions

“…[74]Mammalian host Bordetella bronchiseptica

1: Cytokines

2: Immune cells

3: Lung, lymph nodes, bacterial growth

xHummert et al . [75]Human host Candida albicans 2: Macrophages, ingested yeast cells, fungal survival strategies3: Fungal growth (fitness)xEswarappa [76]Mammalian hostPathogenic bacteria (persistent infections) 1, 2: Extra-, intra-cellular compartments and defence mechanisms3: Bacterial growthxTierney et al . [77]Murine host Candida albicans

1: Gene expression, cytokines

2: Innate immune cells

xBoswell et al .…”

“…With a more phenotypic and generalized view, game theory can also be applied to model the interaction between pathogens and humans or the interaction between different pathogens. For example, this approach was used to understand what advantages the human fungal pathogen C. albicans experiences by changing its morphological form [75, 90] in the context of interacting with the host's immune cells. Additionally, persistent bacterial infection was described by developing a game theoretical model; predictions regarding persistent bacterial infections were drawn by considering the ability of a pathogen to survive extracellularly and intracellularly, within an immune cell [76].…”

Systems Biology of Fungal Infection

“…The initial setup of the interaction model can be arranged by implementing simple interaction rules of cellular behavior based on phenomenological knowledge. An extension toward a complex rule-system is also conceivable as well as the implementation of specific strategic behavior of the pathogenic fungi, as recently unraveled by Hummert et al (2010), by applying methods of game theory. It would also be conceivable to include cell-cell interactions by considering interacting molecules at the cellular surface and their subsequent impact on internal and external signaling.…”