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To obtain essential nutrients, <jats:italic>Toxoplasma<\/jats:italic> must transport molecules across the PVM, a process mediated by the secreted parasite proteins GRA17 and GRA23. These proteins form pores in the PVM through which small molecules can diffuse in and out of the PV. <jats:italic>GRA17<\/jats:italic> and <jats:italic>GRA23<\/jats:italic> are synthetically lethal, suggesting that at least one pore type is essential for parasite survival. In the \u2018nutrient sensitized\u2019 \u0394<jats:italic>gra17<\/jats:italic> strain it is likely that other <jats:italic>Toxoplasma<\/jats:italic> genes become essential, because they mediate nutrient acquisition from the host or are involved in the trafficking of GRA23 to the PVM. To identify these genes, a genome-wide loss-of-function screen was performed in wild-type and \u0394<jats:italic>gra17<\/jats:italic> parasites, which identified multiple genes that were synthetically sick\/lethal with <jats:italic>GRA17<\/jats:italic>. Several of these genes were involved in the correct localization of GRAs, including GRA17\/GRA23, to the PVM. One of the top hits, GRA72, was predicted to form a pore on the PVM, and its deletion led to the formation of enlarged \u201cbubble vacuoles\u201d with reduced PVM small molecule permeability, similar to what was previously observed for \u0394<jats:italic>gra17<\/jats:italic> parasites. Furthermore, \u0394<jats:italic>gra72<\/jats:italic> parasites had reduced <jats:italic>in vitro<\/jats:italic> growth and virulence in mice. These findings suggest that in the absence of GRA17, other genes become essential, likely because they play a role in the proper localization of GRA23 (and other GRAs) or because they determine host-derived nutrient acquisition at the PVM.<\/jats:p>","DOI":"10.1371\/journal.ppat.1011543","type":"journal-article","created":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T17:56:42Z","timestamp":1690480602000},"page":"e1011543","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":28,"title":["Genome-wide CRISPR screen identifies genes synthetically lethal with GRA17, a nutrient channel encoding gene in Toxoplasma"],"prefix":"10.1371","volume":"19","author":[{"given":"Tatiana C.","family":"Paredes-Santos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mebratu A.","family":"Bitew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Swale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Rodriguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shruthi","family":"Krishnamurthy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parag","family":"Maru","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lamba Omar","family":"Sangar\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0289-7109","authenticated-orcid":true,"given":"Jeroen P. 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