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bioRxiv · 10.1101/660753

Identification of a master regulator of differentiation in Toxoplasma

Waldman, B. S.·Schwarz, D.·Wadsworth, M. H.·Saeij, J. P. J.·Shalek, A. K.·Lourido, S.
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Abstract

Toxoplasma gondii chronically infects a quarter of the worlds 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 Toxoplasma differentiation, and will inform prevention and treatment of chronic infection.

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Waldman, B. S., Schwarz, D., Wadsworth, M. H., Saeij, J. P. J., Shalek, A. K., Lourido, S.. 2019-06-05. Identification of a master regulator of differentiation in Toxoplasma. https://doi.org/10.1101/660753

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