Constitutive upregulation of transcription factors underlies permissive bradyzoite differentiation in a natural isolate of Toxoplasma gondii

Jing Xia, Yong Fu, Wanyi Huang, Taher Uddin, L. David Sibley

Research output: Contribution to journalArticlepeer-review

Abstract

Toxoplasma gondii bradyzoites play a critical role in pathology due to their long-term persistence in intermediate hosts and their potential to reactivate, resulting in severe diseases in immunocompromised individuals. Currently, there is no effective treatment for eliminating bradyzoites. Hence, better in vitro models of T. gondii bradyzoite development would facilitate identification of therapeutic targets for bradyzoites. Herein, we characterized a natural isolate of T. gondii, called Tg68, which showed slower in vitro replication of tachyzoites, and permissive bradyzoite development under stress conditions in vitro. Transcriptional analysis revealed constitutive expression in Tg68 tachyzoites of the key regulators of bradyzoite development including BFD1, BFD2, and several AP2 factors. Consistent with this finding, Tg68 tachyzoites expressed high levels of bradyzoite-specific genes including BAG1, ENO1, and LDH2. Moreover, after stress-induced differentiation, Tg68 bradyzoites exhibited gene expression profiles of mature bradyzoites, even at early time points. These data suggest that Tg68 tachyzoites exist in a pre-bradyzoite stage primed to readily develop into mature bradyzoites under stress conditions in vitro. Tg68 presents a novel model for differentiation in vitro that will serve as a useful tool for the investigation of bradyzoite biology and the development of therapeutics.

Original languageEnglish
JournalmBio
Volume15
Issue number9
DOIs
StatePublished - Sep 2024

Keywords

  • Apetala 2 transcription factor
  • Chronic infection
  • stress-induced differentiation
  • tissue cyst

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