A Genome-wide CRISPR Screen in Toxoplasma Identifies Essential Apicomplexan Genes
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nihms810568.pdf
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Author(s)
Sidik, Saima M.
Huet, Diego
Huynh, My-Hang
Thiru, Prathapan
Saeij, Jeroen P.J.
Carruthers, Vern B.
Lourido, Sebastian
Ganesan, Suresh M.
Nasamu, Armiyaw Sebastian
Niles, Jacquin
Date Issued
September 2016
Journal
Cell
Publisher
Elsevier BV
Citation
Sidik, Saima M., et al. “A Genome-Wide CRISPR Screen in Toxoplasma Identifies Essential Apicomplexan Genes.” Cell, vol. 166, no. 6, Sept. 2016, pp. 1423-1435.e12. © 2016 Elsevier Inc.
Version
Final published version
Abstract
Apicomplexan parasites are leading causes of human and livestock diseases such as malaria and toxoplasmosis, yet most of their genes remain uncharacterized. Here, we present the first genome-wide genetic screen of an apicomplexan. We adapted CRISPR/Cas9 to assess the contribution of each gene from the parasite Toxoplasma gondii during infection of human fibroblasts. Our analysis defines ∼200 previously uncharacterized, fitness-conferring genes unique to the phylum, from which 16 were investigated, revealing essential functions during infection of human cells. Secondary screens identify as an invasion factor the claudin-like apicomplexan microneme protein (CLAMP), which resembles mammalian tight-junction proteins and localizes to secretory organelles, making it critical to the initiation of infection. CLAMP is present throughout sequenced apicomplexan genomes and is essential during the asexual stages of the malaria parasite Plasmodium falciparum. These results provide broad-based functional information on T. gondii genes and will facilitate future approaches to expand the horizon of antiparasitic interventions. Keywords: Apicomplexan parasites; host-pathogen interactions; genome-wide CRISPR screen; eukaryotic pathogen; toxoplasmosis; malaria; host-cell invasion
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.CELL.2016.08.019
