A Genome-wide CRISPR Screen in Toxoplasma Identifies Essential Apicomplexan Genes.
Cell
; 166(6): 1423-1435.e12, 2016 Sep 08.
Article
en En
| MEDLINE
| ID: mdl-27594426
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 â¼200 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Toxoplasma
/
Proteínas Protozoarias
/
Apicomplexa
/
Estudio de Asociación del Genoma Completo
/
Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas
/
Interacciones Huésped-Parásitos
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Cell
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos