ApiAP2 factors as candidate regulators of stochastic commitment to merozoite production in Theileria annulata

The ability of vector-borne Apicomplexan parasites (Babesia, Plasmodium and Theileria) to change from one life-cycle stage to the next is critical for establishment of infection and transmission to new hosts. Stage differentiation steps of both Plasmodium and Theileria are known to involve stochastic transition through an intermediate form to a point that commits the cell to generate the next stage in the life-cycle. In this study we have identified genes encoding ApiAP2 DNA binding proteins in Theileria annulata that are differentially expressed during differentiation from the macroschizont stage, through merozoite production (merogony) to the piroplasm stage. The results provide evidence that the ApiAp2 factor in Theileria that possesses the orthologue of the Plasmodium AP2-G domain may also operate to regulate gametocytogenesis, and that progression to merogony is promoted by the ability of a merozoite DNA binding protein to preferentially up-regulate its own production. In addition, identification of multiple ApiAP2 DNA binding domains that bind related motifs within and across vector-borne Apicomplexan genera lead to the proposal that the mechanisms that promote the transition from asexual to sexual replication will show a degree of conservation