Evidence map›Paper›PMID 38977907›Full record

ArticleNature microbiology2024

CRISPR-based functional profiling of the Toxoplasma gondii genome during acute murine infection.

Christopher J Giuliano, Kenneth J Wei, Faye M Harling, Benjamin S Waldman, Madeline A Farringer, Elizabeth A Boydston, Tammy C T Lan, Raina W Thomas, Alice L Herneisen, Allen G Sanderlin and 3 more

Abstract read
In one paragraph

Article in Nature microbiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
–field-weighted citation impact
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

21 citing papers in PubMed.

  1. Article
  2. bioRxiv : the preprint server for biology · 2026
    Article
  3. A pooled image-based CRISPR screen identifies EAF1 as abioRxiv : the preprint server for biology · 2026
    Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Surface antigen SAG1 mediatesInfection and immunity · 2025
    Article
  11. Article
  12. Article
  13. TheMolecular biology of the cell · 2025
    Article
  14. Article
  15. Article
  16. ThebioRxiv : the preprint server for biology · 2024
    Article
  17. Article
  18. A Combination of Four Nuclear Targeted Effectors ProtectsbioRxiv : the preprint server for biology · 2023
    Article
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Christopher J GiulianoWhitehead Institute, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-0586-6095
Kenneth J WeiWhitehead Institute, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-7168-3481
Faye M HarlingWhitehead Institute, Cambridge, MA, USA.
Benjamin S WaldmanWhitehead Institute, Cambridge, MA, USA.
Madeline A FarringerDivision of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA.
Elizabeth A BoydstonWhitehead Institute, Cambridge, MA, USA.
Tammy C T LanWhitehead Institute, Cambridge, MA, USA.
Raina W ThomasWhitehead Institute, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-8027-3460
Alice L HerneisenWhitehead Institute, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-3368-0893
Allen G SanderlinBiology Department, MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-9230-9157
Isabelle CoppensDepartment of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
Jeffrey D DvorinDivision of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-5883-7271
Sebastian LouridoWhitehead Institute, Cambridge, MA, USA. lourido@wi.mit.edu.ORCID http://orcid.org/0000-0002-5237-1095

Funding

The Graduate Program in Tropical Infectious Diseases (GPiTID)T32AI049928 · NIAID · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI Flaminia Catteruccia, Phyllis J. Kanki · 2001 to 2026
$5.0M
Development and maintenance of chronic toxoplasmosisR01AI158501 · NIAID · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI LOURIDO, SEBASTIAN · 2021 to 2025
$3.3M
Molecular mechanisms of schizogony in malaria parasitesR01AI145941 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI DVORIN, JEFFREY D · 2019 to 2023
$3.1M
Control of parasite invasion by a microneme protein complex conserved in ApicomplexansR01AI144369 · NIAID · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI LOURIDO, SEBASTIAN · 2020 to 2024
$2.4M
NIAID NIH HHS R01 AI144369NIAID NIH HHS R01 AI145941NIAID NIH HHS R01 AI158501NIAID NIH HHS T32 AI049928
6 · The paper itself

Abstract

Examining host-pathogen interactions in animals can capture aspects of infection that are obscured in cell culture. Using CRISPR-based screens, we functionally profile the entire genome of the apicomplexan parasite Toxoplasma gondii during murine infection. Barcoded gRNAs enabled bottleneck detection and mapping of population structures within parasite lineages. Over 300 genes with previously unknown roles in infection were found to modulate parasite fitness in mice. Candidates span multiple axes of host-parasite interaction. Rhoptry Apical Surface Protein 1 was characterized as a mediator of host-cell tropism that facilitates repeated invasion attempts. GTP cyclohydrolase I was also required for fitness in mice and druggable through a repurposed compound, 2,4-diamino-6-hydroxypyrimidine. This compound synergized with pyrimethamine against T. gondii and malaria-causing Plasmodium falciparum parasites. This work represents a complete survey of an apicomplexan genome during infection of an animal host and points to novel interfaces of host-parasite interaction.

Indexed as

Genome, ProtozoanHost-Parasite InteractionsToxoplasmaAnimalsAntiprotozoal AgentsClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsDisease Models, AnimalFemaleMiceProtozoan ProteinsPyrimethamineToxoplasmosisToxoplasmosis, AnimalAntiprotozoal AgentsProtozoan ProteinsPyrimethamine

Identifiers

PMID38977907
PMCPMC11811839

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.