Fig. 7: Model illustrating the non-linear life cycle and multifunctional nature of bradyzoites within heterogeneous tissue cysts.

Our findings reveal that bradyzoites both positive and negative for SRS22A antigen can coexist within the same tissue cyst. SRS22A expression distinguishes two bradyzoite subtypes that initiate different developmental pathways: SRS22A+ bradyzoite infection initiates bradyzoite recrudescence into fast-replicating tachyzoites, while infections with SRS22A− bradyzoites initiates bradyzoite-to-bradyzoite replication. A large fraction of SRS22A+ bradyzoites are BAG1-, and it is possible these bradyzoites may initiate the definitive life cycle in feline host, which will require alterations in AP2 factor expression. Rhoptry related gene expression is triggered by egress and invasion events. We have found that a group of in vivo bradyzoites (Group A) possesses this pattern of gene expression, which may help explain the large number of documented parasite invasion events that do not lead to productive infections of host cells. Created in BioRender. Ulu, A. (2026) https://BioRender.com/vup91un.