Evidence map›Paper›PMID 37498952›Full record

ArticlePLoS pathogens2023

Genome-wide CRISPR screen identifies genes synthetically lethal with GRA17, a nutrient channel encoding gene in Toxoplasma.

Tatiana C Paredes-Santos, Mebratu A Bitew, Christopher Swale, Felipe Rodriguez, Shruthi Krishnamurthy, Yifan Wang, Parag Maru, Lamba Omar Sangaré, Jeroen P J Saeij

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
9.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 35 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. A two-membrane gateway for monocarboxylates couples host glycolysis tobioRxiv : the preprint server for biology · 2026
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  5. Dense granule proteins: key mediators ofFrontiers in medicine · 2026
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  7. bioRxiv : the preprint server for biology · 2025
    Article
  8. Article
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  12. Article
  13. Article
  14. Article
  15. TwomBio · 2024
    Article
  16. GRA47 and GRA72 arebioRxiv : the preprint server for biology · 2023
    Article
  17. Review
  18. Dissecting EXP2 sequence requirements for protein export in malaria parasites.Frontiers in cellular and infection microbiology · 2023
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 2 countries.

Tatiana C Paredes-SantosDepartment of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California Davis, Davis, California, United States of America.
Mebratu A BitewDepartment of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California Davis, Davis, California, United States of America.
Christopher SwaleTeam Host-Pathogen Interactions and Immunity to Infection, Institute for Advanced Biosciences (IAB), INSERM U1209, CNRS UMR5309, University Grenoble Alpes, Grenoble, France.
Felipe RodriguezDepartment of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California Davis, Davis, California, United States of America.
Shruthi KrishnamurthyDepartment of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California Davis, Davis, California, United States of America.
Yifan WangDepartment of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California Davis, Davis, California, United States of America.
Parag MaruDepartment of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California Davis, Davis, California, United States of America.
Lamba Omar SangaréDepartment of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California Davis, Davis, California, United States of America.
Jeroen P J SaeijDepartment of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California Davis, Davis, California, United States of America.ORCID 0000-0003-0289-7109
University of California, Davis · USCentre National de la Recherche Scientifique · FR

Funding

Genome-wide CRISPR/Cas9-mediated loss-of-function screens to identify Toxoplasma genes that determine fitness in gamma interferon-stimulated human cellsR21AI149071 · NIAID · UNIVERSITY OF CALIFORNIA AT DAVIS · PI SAEIJ, JEROEN · 2020 to 2021
$432k
Synthetic lethality screens in a nutrient sensitized Toxoplasma strain to identify novel proteins that mediate nutrient acquisition in chronic Toxoplasma infection.R21AI150326 · NIAID · UNIVERSITY OF CALIFORNIA AT DAVIS · PI SAEIJ, JEROEN · 2020 to 2021
$432k
Identify Toxoplasma genes that determine in vivo fitness with CRISPR-Cas9 genetic screensR21AI151084 · NIAID · UNIVERSITY OF CALIFORNIA AT DAVIS · PI SAEIJ, JEROEN · 2020 to 2021
$432k
NIAID NIH HHS R21 AI149071NIAID NIH HHS R21 AI150326NIAID NIH HHS R21 AI151084
6 · The paper itself

Abstract

Toxoplasma gondii is a parasite that replicates within a specialized compartment called the parasitophorous vacuole (PV), which is surrounded by the PV membrane (PVM). To obtain essential nutrients, Toxoplasma 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. GRA17 and GRA23 are synthetically lethal, suggesting that at least one pore type is essential for parasite survival. In the 'nutrient sensitized' Δgra17 strain it is likely that other Toxoplasma 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 Δgra17 parasites, which identified multiple genes that were synthetically sick/lethal with GRA17. 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 "bubble vacuoles" with reduced PVM small molecule permeability, similar to what was previously observed for Δgra17 parasites. Furthermore, Δgra72 parasites had reduced in vitro 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.

Indexed as

ToxoplasmaAnimalsClustered Regularly Interspaced Short Palindromic RepeatsMiceNutrientsProtozoan ProteinsVacuolesNutrientsProtozoan Proteins

Identifiers

PMID37498952
PMCPMC10409377
OpenAlexW4385325689

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.