Complement immune evasion of Candida albicans

In this study we analyze the the immune evasive pathogen C. albicans. The secreted pH regulated antigen 1 (Pra1) is a protease and cleaves C3, the key molecule for cell opsonization. The paradox of this mechanism is that this cleavage of C3 produces a molecule that is very similar to the opsonin C3b. At a first glance it is not obvious why this protease has a regulatory influence on the system. This paradox is to be deciphered with a mathematical model.

Experimental Collaborators

Model of the Pra1 interaction with the complement molecule C3 and its cleavage products.

Model of the Pra1 interaction with the complement molecule C3 and its cleavage products. Fluid phase Pra1f binds to C3f and cleaves it into fragments C3aLf and C3bLf. In addition, $Pra1^f$ binds to the cleavage products C3af, C3bf, C3aLf and C3bLf and blocks their effector function. The molecule C3bLf can bind to the cell surface like C3bf and there enhance complement activation via the C3-convertase of the alternative pathway or it is inactivated by regulators and cleaved to iC3bLs.

For this purpose, the existing DynaCoSys model is extended to include the dynamics of Pra1 and its cleavage products. The deviation of opsonization on the surface and of the molecules in the fluid around the cell will be analyzed in comparison to a cell without Pra1 secretion.

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