Identification of a master regulator of differentiation in<i>Toxoplasma</i>
SUMMARY Toxoplasma gondiichronically 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 controlToxoplasmadifferentiation, and will inform prevention and treatment of chronic infection..
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Preprint| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
bioRxiv.org - (2023) vom: 17. Sept. Zur Gesamtaufnahme - year:2023 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Waldman, Benjamin S. [VerfasserIn] |
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| doi: |
10.1101/660753 |
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| PPN (Katalog-ID): |
XBI000536679 |
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| 100 | 1 | |a Waldman, Benjamin S. |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Identification of a master regulator of differentiation in<i>Toxoplasma</i> |
| 264 | 1 | |c 2023 | |
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| 520 | |a SUMMARY Toxoplasma gondiichronically 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 controlToxoplasmadifferentiation, and will inform prevention and treatment of chronic infection. | ||
| 650 | 4 | |a Biology |7 (dpeaa)DE-84 | |
| 650 | 4 | |a 570 |7 (dpeaa)DE-84 | |
| 700 | 1 | |a Schwarz, Dominic |4 aut | |
| 700 | 1 | |a Wadsworth, Marc H. |4 aut | |
| 700 | 1 | |a Saeij, Jeroen P. |4 aut | |
| 700 | 1 | |a Shalek, Alex K. |4 aut | |
| 700 | 1 | |a Lourido, Sebastian |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t bioRxiv.org |g (2023) vom: 17. Sept. |
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| 856 | 4 | 0 | |u https://doi.org/10.1016/j.cell.2019.12.013 |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1101/660753 |z kostenfrei |3 Volltext |
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