Evidence map›Paper›PMID 37081202›Full record

ArticleNature microbiology2023

A positive feedback loop controls Toxoplasma chronic differentiation.

M Haley Licon, Christopher J Giuliano, Alex W Chan, Sundeep Chakladar, Julia N Eberhard, Lindsey A Shallberg, Sambamurthy Chandrasekaran, Benjamin S Waldman, Anita A Koshy, Christopher A Hunter and 1 more

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Nature microbiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
14.9field-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

33 citing papers in PubMed, 54 citations in OpenAlex.

  1. Article
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  6. Review
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  8. Article
  9. Article
  10. Toxoplasma gondii and the Brain: Frenemies? Or Just Outright Foes?Journal of the Pediatric Infectious Diseases Society · 2025
    Review
  11. AP2X-8 Is Important for Tachyzoite Growth and Bradyzoite Differentiation ofAnimals : an open access journal from MDPI · 2025
    Article
  12. Article
  13. mSphere · 2025
    Article
  14. Article
  15. Novel Drug Targets for the Bradyzoite Form ofResearch and reports in tropical medicine · 2025
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 1 country.

M Haley LiconWhitehead Institute, Cambridge, MA, USA.
Christopher J GiulianoWhitehead Institute, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-0586-6095
Alex W ChanWhitehead Institute, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-5444-5756
Sundeep ChakladarBiology Department, Massachusetts Institute of Technology, Cambridge, MA, USA.
Julia N EberhardDepartment of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Lindsey A ShallbergDepartment of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Sambamurthy ChandrasekaranBIO5 Institute, University of Arizona, Tucson, AZ, USA.
Benjamin S WaldmanWhitehead Institute, Cambridge, MA, USA.
Anita A KoshyBIO5 Institute, University of Arizona, Tucson, AZ, USA.
Christopher A HunterDepartment of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-3092-1428
Sebastian LouridoWhitehead Institute, Cambridge, MA, USA. lourido@wi.mit.edu.ORCID http://orcid.org/0000-0002-5237-1095
Whitehead Institute for Biomedical Research · USUniversity of Pennsylvania · USUniversity of Arizona · USMassachusetts Institute of Technology · US

Funding

Neuronal Latency and ToxoplasmaR01AI157247 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI CHRISTOPHER A HUNTER, Anita Koshy · 2020 to 2026
$4.7M
Development and maintenance of chronic toxoplasmosisR01AI158501 · NIAID · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI LOURIDO, SEBASTIAN · 2021 to 2025
$3.3M
NIAID NIH HHS R01 AI157247NIAID NIH HHS R01 AI158501
6 · The paper itself

Abstract

Successful infection strategies must balance pathogen amplification and persistence. In the obligate intracellular parasite Toxoplasma gondii this is accomplished through differentiation into dedicated cyst-forming chronic stages that avoid clearance by the host immune system. The transcription factor BFD1 is both necessary and sufficient for stage conversion; however, its regulation is not understood. In this study we examine five factors that are transcriptionally activated by BFD1. One of these is a cytosolic RNA-binding protein of the CCCH-type zinc-finger family, which we name bradyzoite formation deficient 2 (BFD2). Parasites lacking BFD2 fail to induce BFD1 and are consequently unable to fully differentiate in culture or in mice. BFD2 interacts with the BFD1 transcript under stress, and deletion of BFD2 reduces BFD1 protein levels but not messenger RNA abundance. The reciprocal effects on BFD2 transcription and BFD1 translation outline a positive feedback loop that enforces the chronic-stage gene-expression programme. Thus, our findings help explain how parasites both initiate and commit to chronic differentiation. This work provides new mechanistic insight into the regulation of T. gondii persistence, and can be exploited in the design of strategies to prevent and treat these key reservoirs of human infection.

Indexed as

ToxoplasmaAnimalsFeedbackGene Expression RegulationHumansMiceTranscription FactorsTranscription Factors

Identifiers

PMID37081202
PMCPMC10520893
OpenAlexW4366481724

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.