Cell. 2016 Sep 1. pii: S0092-8674(16)31070-4. doi: 10.1016/j.cell.2016.08.019. [Epub ahead of print]
Sidik SM1,
Huet D1,
Ganesan SM2,
Huynh MH3,
Wang T4,
Nasamu AS2,
Thiru P1,
Saeij JP5,
Carruthers VB3,
Niles JC2,
Lourido S6.
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.
Copyright © 2016 Elsevier Inc. All rights reserved.
KEYWORDS:
Apicomplexan parasites; eukaryotic pathogen; genome-wide CRISPR screen; host-cell invasion; host-pathogen interactions; malaria; toxoplasmosis
- [PubMed - as supplied by publisher]
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