Development of bradyzoites within tissue cysts in vivo. Development of bradyzoites within tissue cysts in vivo. All tissue cysts arise from tachyzoites where the high growth rate and synchrony in replication account for a high mean TgIMC3 intensity. Immune pressure contributes to stage conversion noted by the development of the tissue cyst wall (orange). The early transitional bradyzoites exhibit reduced growth rate (noted by the variability in TgIMC3 intensity) relative to tachyzoites while still retaining the capacity for significant replication with a high degree of synchrony within the tissue cyst. The proposed intermediate bradyzoites within a tissue cyst exhibit greater asynchrony in replication depicted by a greater range of TgIMC3 intensities. We hypothesize that the retained replicative potential of both the transitional and intermediate bradyzoite populations contributes to a lower threshold for reactivation. Accordingly, these cysts possess the highest likelihood of both spontaneous reactivation and reactivation in the context of immune suppression. Finally, we hypothesize that progression toward deeper dormancy resulting in the terminal bradyzoite-possessing cysts may have a lower threshold for reactivation within the host but are geared for transmission to the next host. The heterogeneity of replication patterns would still permit a low level of sporadic replication within these terminal tissue cysts. Together, we propose that tissue cysts, while genetically clonal, are physiologically and phenotypically varied with regard to the bradyzoites they house. Elizabeth Watts et al. mBio 2015; doi:10.1128/mBio.01155-15