| Autor: |
Wang, Yifan, Sangare, Lamba Omar, Paredes-Santos, Tatiana C., Krishnamurthy, Shruthi, Hassan, Musa, Furuta, Anna M., Markus, Benedikt M., Lourido, Sebastian, Saeij, Jeroen P.J. |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
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| Zdroj: |
Wang, Y, Sangare, L O, Paredes-Santos, T C, Krishnamurthy, S, Hassan, M, Furuta, A M, Markus, B M, Lourido, S & Saeij, J P J 2019 ' A genome-wide loss-of-function screen identifies Toxoplasma gondii genes that determine fitness in interferon gamma-activated murine macrophages ' bioRxiv . https://doi.org/10.1101/867705 |
| DOI: |
10.1101/867705 |
| Popis: |
Macrophages play an essential role in the early immune response against Toxoplasma and are the cell type preferentially infected by the parasite in vivo. Interferon gamma (IFNγ) elicits a variety of anti-Toxoplasma activities in macrophages. Using a genome-wide CRISPR screen we identified ∼130 Toxoplasma genes that determine parasite fitness in naїve macrophages and ∼466 genes that determine fitness in IFNγ-stimulated murine macrophages, seven of which we investigated and confirmed. We show that one of these genes encodes dense granule protein GRA45, which contains a putative chaperone-like domain, and which we show is critical in preventing other GRA effectors from aggregating. Parasites lacking GRA45 mislocalize GRA effectors upon secretion, are more susceptible to IFNγ-mediated growth inhibition, and have reduced virulence in mice. Our results provide a resource for the community to further explore the function of Toxoplasma genes that determine fitness in IFNγ-stimulated macrophages. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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