Identification of a Master Regulator of Differentiation in Toxoplasma

  • Biology
  • Infectious Disease
  • Microbiology
  • Marc Wadsworth
  • Alex K. Shalek
  • Waldman B.S. et al.▾
    Waldman B.S., Schwarz D., Wadsworth II M.H., Saeij J.P.J., Shalek A.K., Lourido S.
  • bioRxiv
  • June, 2019
Biology
Infectious Disease
Microbiology
Marc Wadsworth
Alex K. Shalek

Abstract

Toxoplasma gondii chronically infects a quarter of the world’s population, and its recrudescence can cause life-threatening disease in immunocompromised individuals and recurrent ocular lesions in the immunocompetent. Chronic stages are established by differentiation of rapidly replicating tachyzoites into slow-growing bradyzoites, which form intracellular cysts resistant to immune clearance and existing therapies. Despite its central role in infection, the molecular basis of chronic differentiation is not understood. Through Cas9-mediated genetic screening and single-cell transcriptional profiling, we identify and characterize a putative transcription factor (BFD1) as necessary and sufficient for differentiation. Translation of BFD1 appears to be stress regulated, and its constitutive expression elicits differentiation in the absence of stress. As a Myb-like factor, BFD1 provides a counterpoint to the ApiAP2 factors which dominate our current view of parasite gene regulation. Overall, BFD1 provides a genetic switch to study and control Toxoplasmadifferentiation, and will inform prevention and treatment of chronic infection.

Identification of a Master Regulator of Differentiation in Toxoplasma