Pyrimidine salvage in as a target for new treatment.

Toxoplasmosis is a common protozoan infection that can have severe outcomes in the immunocompromised and during pregnancy, but treatment options are limited. Recently, nucleotide metabolism has received much attention as a target for new antiprotozoal agents and here we focus on pyrimidine salvage by as a drug target. Whereas uptake of [H]-cytidine and particularly [H]-thymidine was at most marginal, [H]-uracil and [H]-uridine were readily taken up.

An model of recrudescence reveals developmental plasticity of the bradyzoite stage.

The classical depiction of the lifecycle is bradyzoite excystation conversion to tachyzoites, cell lysis, and immune control, followed by the reestablishment of bradyzoites and cysts. In contrast, we show that tachyzoite growth slows independent of the host immune response at a predictable time point following excystation. Furthermore, we demonstrate a host cell-dependent pathway of continuous amplification of the cyst-forming bradyzoite population.