Toxoplasma gondii AP2IX-4 regulates gene expression during bradyzoite development

Sherri Huang, Michael J. Holmes, Joshua B. Radke, Dong Pyo Hong, Ting Kai Liu, Michael W. White, William J. Sullivan

Research output: Contribution to journalArticle

17 Scopus citations


Toxoplasma gondii is a protozoan parasite of great importance to human and animal health. In the host, this obligate intracellular parasite persists as a tissue cyst that is imperceptible to the immune response and unaffected by current therapies. The tissue cysts facilitate transmission through predation and give rise to chronic cycles of toxoplasmosis in immunocompromised patients. Transcriptional changes accompany conversion of the rapidly replicating tachyzoites into the encysted bradyzoites, and yet the mechanisms underlying these alterations in gene expression are not well defined. Here we show that AP2IX-4 is a nuclear protein exclusively expressed in tachyzoites and bradyzoites undergoing division. Knockout of AP2IX-4 had no discernible effect on tachyzoite replication but resulted in a reduced frequency of tissue cyst formation following alkaline stress induction-a defect that is reversible by complementation. AP2IX-4 has a complex role in regulating bradyzoite gene expression, as the levels of many bradyzoite mRNAs dramatically increased beyond those seen under conditions of normal stress induction in AP2IX-4 knockout parasites exposed to alkaline media. The loss of AP2IX-4 also resulted in a modest virulence defect and reduced cyst burden in chronically infected mice, which was reversed by complementation. These findings illustrate that the transcriptional mechanisms responsible for tissue cyst development operate across the intermediate life cycle from the dividing tachyzoite to the dormant bradyzoite.

Original languageEnglish (US)
Article numbere00054-17
Issue number2
StatePublished - Mar 1 2017


  • ApiAP2
  • Apicomplexan parasites
  • Differentiation
  • Gene expression
  • Intracellular parasites
  • Transcription

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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  • Cite this

    Huang, S., Holmes, M. J., Radke, J. B., Hong, D. P., Liu, T. K., White, M. W., & Sullivan, W. J. (2017). Toxoplasma gondii AP2IX-4 regulates gene expression during bradyzoite development. mSphere, 2(2), [e00054-17].