Identification of a Master Regulator of Differentiation in Toxoplasma
Name
1-s2.0-S0092867419313753-main.pdf
Description
Published version
Size
11.65 MB
Format
Adobe PDF
Checksum (MD5)
93846c4aca5d273b49b7a6b8fce7b2fe
Author(s)
Waldman, Benjamin S
Schwarz, Dominic
Wadsworth, Marc H
Saeij, Jeroen P
Shalek, Alex K
Lourido, Sebastian
Date Issued
2020
Journal
Cell
Publisher
Elsevier BV
Version
Final published version
Abstract
© 2019 The Author(s) 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. Acute-stage tachyzoites differentiate into chronic-stage bradyzoites, which form intracellular cysts resistant to immune clearance and existing therapies. The molecular basis of this differentiation is unknown, despite being efficiently triggered by stresses in culture. Through Cas9-mediated screening and single-cell profiling, we identify a Myb-like transcription factor (BFD1) necessary for differentiation in cell culture and in mice. BFD1 accumulates during stress and its synthetic expression is sufficient to drive differentiation. Consistent with its function as a transcription factor, BFD1 binds the promoters of many stage-specific genes and represents a counterpoint to the ApiAP2 factors that dominate our current view of parasite gene regulation. BFD1 provides a genetic switch to study and control Toxoplasma differentiation and will inform prevention and treatment of chronic infections.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Massachusetts Institute of Technology. Department of Chemistry
Koch Institute for Integrative Cancer Research at MIT
Ragon Institute of MGH, MIT and Harvard
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
10.1016/J.CELL.2019.12.013
https://doi.org/10.1016/J.CELL.2019.12.013
